External signal-activated liposomal drug delivery systems

Modern drug discovery gives rise to a great number of potential new therapeutic agents, but in some cases the efficient treatment of patient may not be achieved because the delivery of active compounds to the target site is insufficient. Thus, drug delivery is one of the major challenges in current pharmaceutical research. Numerous nanoparticle-based drug carriers, e.g. liposomes, have been developed for enhanced drug delivery and targeting. Drug targeting may enhance the efficiency of the treatment and, importantly, reduce unwanted side effects by decreasing drug distribution to non-target tissues. Liposomes are biocompatible lipid-based carriers that have been studied for drug delivery during the last 40 years. They can be functionalized with targeting ligands and sensing materials for triggered activation. In this study, various external signal-assisted liposomal delivery systems were developed. Signals can be used to modulate drug permeation or release from the liposome formulation, and they provide accurate control of time, place and rate of activation. The study involved three types of signals that were used to trigger drug permeation and release: electricity, heat and light. Electrical stimulus was utilized to enhance the permeation of liposomal DNA across the skin. Liposome/DNA complex-mediated transfections were performed in tight rat epidermal cell model. Various transfection media and current intensities were tested, and transfection efficiency was evaluated non-invasively by monitoring the concentration of secreted reporter protein in cell culture medium. Liposome/DNA complexes produced gene expression, but electrical stimulus did not enhance the transfection efficiency significantly. Heat-sensitive liposomal drug delivery system was developed by coating liposomes with biodegradable and thermosensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate polymer. Temperature-triggered liposome aggregation and contents release from liposomes were evaluated. The cloud point temperature (CP) of the polymer was set to 42 °C. Polymer-coated liposome aggregation and contents release were observed above CP of the polymer, while non-coated liposomes remained intact. Polymer precipitates above its CP and interacts with liposomal bilayers. It is likely that this induces permeabilization of the liposomal membrane and contents release. Light-sensitivity was introduced to liposomes by incorporation of small (< 5 nm) gold nanoparticles. Hydrophobic and hydrophilic gold nanoparticles were embedded in thermosensitive liposomes, and contents release was investigated upon UV light exposure. UV light-induced lipid phase transitions were examined with small angle X-ray scattering, and light-triggered contents release was shown also in human retinal pigment epithelial cell line. Gold nanoparticles absorb light energy and transfer it into heat, which induces phase transitions in liposomes and triggers the contents release. In conclusion, external signal-activated liposomes offer an advanced platform for numerous applications in drug delivery, particularly in the localized drug delivery. Drug release may be localized to the target site with triggering stimulus that results in better therapeutic response and less adverse effects. Triggering signal and mechanism of activation can be selected according to a specific application.

Epidemiological data of seasonal variation in mood and behaviour

The aim of this study was to measure seasonal variation in mood and behaviour. The dual vulnerability and latitude effect hypothesis, the risk of increased appetite, weight and other seasonal symptoms to develop metabolic syndrome, and perception of low illumination in quality of life and mental well-being were assessed. These variations are prevalent in persons who live in high latitudes and need balancing of metabolic processes to adapt to environmental changes due to seasons. A randomized sample of 8028 adults aged 30 and over (55% women) participated in an epidemiological health examination study, The Health 2000, applying the probability proportional to population size method for a range of socio-demographic characteristics. They were present in a face-to-face interview at home and health status examination. The questionnaires included the modified versions of the Seasonal Pattern Assessment Questionnaire (SPAQ) and Beck Depression Inventory (BDI), the Health Related Quality of Life (HRQoL) instrument 15D, and the General Health Questionnaire (GHQ). The structured and computerized Munich Composite International Diagnostic Interview (M-CIDI) as part of the interview was used to assess diagnoses of mental disorders, and, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria were assessed using all the available information to detect metabolic syndrome. A key finding was that 85% of this nationwide representative sample had seasonal variation in mood and behaviour. Approximately 9% of the study population presented combined seasonal and depressive symptoms with a significant association between their scores, and 2.6% had symptoms that corresponded to Seasonal Affective Disorder (SAD) in severity. Seasonal variations in weight and appetite are two important components that increase the risk of metabolic syndrome. Other factors such as waist circumference and major depressive disorder contributed to the metabolic syndrome as well. Persons reported of having seasonal symptoms were associated with a poorer quality of life and compromised mental well-being, especially if indoors illumination at home and/or at work was experienced as being low. Seasonal and circadian misalignments are suggested to associate with metabolic disorders, and could be remarked if individuals perceive low illumination levels at home and/or at work that affect the health-related quality of life and mental well-being. Keywords: depression, health-related quality of life, illumination, latitude, mental well-being, metabolic syndrome, seasonal variation, winter.

Mannans as film formers and emulsion stabilizers

Mannans are abundant plant polysaccharides found in the endosperm of certain leguminous seeds (guar gum galactomannan, GG; locust bean gum galactomannan, LBG), in the tuber of the konjac plant (konjac glucomannan, KGM), and in softwoods (galactoglucomannan, GGM). This study focused on the effects of the chemical structure of mannans on their film-forming and emulsion-stabilizing properties. Special focus was on spruce GGM, which is an interesting new product from forest biorefineries. A plasticizer was needed for the formation of films from mannans other than KGM and the optimal proportion was 40% (w/w of polymers) glycerol or sorbitol. Galactomannans with lower galactose content (LBG, modified GG) produced films with higher elongation at break and tensile strength. The mechanical properties of GG-based films were improved by decreasing the degree of polymerization of the polysaccharide with moderate mannanase treatments. The improvement of mechanical properties of GGM-based films was sought by blending GGM with each of poly(vinyl alcohol) (PVOH), corn arabinoxylan (cAX), and KGM. Adding other polymers increased the elongation at break of GGM blend films. The tensile strength of films increased with increasing amounts of PVOH and KGM, but the effect of cAX was the opposite. Dynamic mechanical analysis showed two separate loss modulus peaks for blends of GGM and PVOH, but a single peak for all other films. Optical and scanning electron microscopy confirmed good miscibility of GGM with cAX and KGM. In contrast, films blended from GGM and PVOH showed phase separation. GGM and KGM were mixed with cellulose nanowhiskers (CNW) to form composite films. Addition of CNW to KGM-based films induced the formation of fiberlike structures with lengths of several millimeters. In GGM-based films, rodlike structures with lengths of tens of micrometers were formed. Interestingly, the notable differences in the film structure did not appear to be related to the mechanical and thermal properties of the films. Permeability properties of GGM-based films were compared to those of films from commercial mannans KGM, GG, and LBG. GGM-based films had the lowest water vapor permeability when compared to films from other mannans. The oxygen permeability of GGM films was of the same magnitude as that of commercial polyethylene / ethylene vinyl alcohol / polyethylene laminate film. The aroma permeability of GGM films was low. All films were transparent in the visible region, but GGM films blocked the light transmission in the ultraviolet region of the spectra. The stabilizing effect of GGM on a model beverage emulsion system was studied and compared to that of GG, LBG, KGM, and cAX. In addition, GG was enzymatically modified in order to examine the effect of the degree of polymerization and the degree of substitution of galactomannans on emulsion stability. Use of GGM increased the turbidity of emulsions both immediately after preparation and after storage of up to 14 days at room temperature. GGM emulsions had higher turbidity than the emulsions containing other mannans. Increasing the storage temperature to +45 ºC led to rapid emulsion breakdown, but a decrease in storage temperature increased emulsion stability after 14 days. A low degree of polymerization and a high degree of substitution of the modified galactomannans were associated with a decrease in emulsion turbidity.

Atomic Layer Deposition of Electroluminescent ZnS, SrS, and BaS Thin Films

The light emitted by flat panel displays (FPD) can be generated in many different ways, such as for example alternating current thin film electroluminescence (ACTFEL), liquid crystal display (LCD), light emitting diode (LED), or plasma display panel (PDP) technologies. In this work, the focus was on ACTFEL devices and the goal was to develop new thin film processes for light emitting materials in ACTFEL devices. The films were deposited with the atomic layer deposition (ALD) method, which has been utilized in the manufacturing of ACTFEL displays since the mid-1980s. The ALD method is based on surface-controlled self-terminated reactions and a maximum of one layer of the desired material can be prepared during one deposition cycle. Therefore, the film thickness can be controlled simply by adjusting the number of deposition cycles. In addition, both large areas and deep trench structures can be covered uniformly. During this work, new ALD processes were developed for the following thin film materials: BaS, CuxS, MnS, PbS, SrS, SrSe, SrTe, SrS1-xSex, ZnS, and ZnS1-xSex. In addition, several ACTFEL devices were prepared where the light emitting material was BaS, SrS, SrS1-xSex, ZnS, or ZnS1-xSex thin film that was doped with Ce, Cu, Eu, Mn, or Pb. The sulfoselenide films were made by substituting the elemental selenium for sulfur on the substrate surface during film deposition. In this way, it was possible to replace a maximum of 90% of the sulfur with selenium, and the XRD analyses indicated that the films were solid solutions. The polycrystalline BaS, SrS, and ZnS thin films were deposited at 180-400, 120-460, and 280-500 °C, respectively, and the processes had a wide temperature range where the growth rate of the films was independent of the deposition temperature. The electroluminescence studies showed that the doped sulfoselenide films resulted in low emission intensity. However, the emission intensities and emission colors of the doped SrS, BaS, and ZnS films were comparable with those found in earlier studies. It was also shown that the electro-optical properties of the different ZnS:Mn devices were different as a consequence of different ZnS:Mn processes. Finally, it was concluded that because the higher deposition temperature seemed to result in a higher emission intensity, the thermal stability of the reactants has a significant role when the light emitting materials of ACTFEL devices are deposited with the ALD method.

Maintaining plant species richness by cattle grazing - mesic semi-natural grasslands as focal habitats

Semi-natural grasslands are the most important agricultural areas for biodiversity. The present study investigates the effects of traditional livestock grazing and mowing on plant species richness, the main emphasis being on cattle grazing in mesic semi-natural grasslands. The two reviews provide a thorough assessment of the multifaceted impacts and importance of grazing and mowing management to plant species richness. It is emphasized that livestock grazing and mowing have partially compensated the suppression of major natural disturbances by humans and mitigated the negative effects of eutrophication. This hypothesis has important consequences for nature conservation: A large proportion of European species originally adapted to natural disturbances may be at present dependent on livestock grazing and / or mowing. Furthermore, grazing and mowing are key management methods to mitigate effects of nutrient-enrichment. The species composition and richness in old (continuously grazed), new (grazing restarting 3-8 years ago) and abandoned (over 10 years) pastures differed consistently across a range of spatial scales, and was intermediate in new pastures compared to old and abandoned pastures. In mesic grasslands most plant species were shown to benefit from cattle grazing. Indicator species of biologically valuable grasslands and rare species were more abundant in grazed than in abandoned grasslands. Steep S-SW-facing slopes are the most suitable sites for many grassland plants and should be prioritized in grassland restoration. The proportion of species trait groups benefiting from grazing was higher in mesic semi-natural grasslands than in dry and wet grasslands. Consequently, species trait responses to grazing and the effectiveness of the natural factors limiting plant growth may be intimately linked High plant species richness of traditionally mowed and grazed areas is explained by numerous factors which operate on different spatial scales. Particularly important for maintaining large scale plant species richness are evolutionary and mitigation factors. Grazing and mowing cause a shift towards the conditions that have occurred during the evolutionary history of European plant species by modifying key ecological factors (nutrients, pH and light). The results of this Dissertation suggest that restoration of semi-natural grasslands by private farmers is potentially a useful method to manage biodiversity in the agricultural landscape. However, the quality of management is commonly improper, particularly due to financial constraints. For enhanced success of restoration, management regulations in the agri-environment scheme need to be defined more explicitly and the scheme should be revised to encourage management of biodiversity.

Glutamatergic Modulation of Cue-Induced Drug-Seeking Behavior in the Rat

The characteristics of drug addiction include compulsive drug use despite negative consequences and re-occurring relapses, returns to drug use after a period of abstinence. Therefore, relapse prevention is one of the major challenges for the treatment of drug addiction. There are three main factors capable of inducing craving for drugs and triggering relapse long after cessation of drug use and dissipation of physical withdrawal signs: stress, re-exposure to the drug, and environmental stimuli (cues) that have been previously associated with drug use. The neurotransmitters dopamine and glutamate have been implicated in the modulation of drug-seeking behavior. The aim of this project was to examine the role of glutamatergic neurotransmission in relapse triggered by conditioned drug-associated stimuli. The focus was on clarifying whether relapse to drug seeking can be attenuated by blockade of glutamate receptors. In addition, as the nucleus accumbens has been proposed to participate in the modulation of drug-seeking behavior, the effects of glutamate receptor blockade in this brain structure on cue-induced relapse were investigated. The studies employed animals models in which rats were trained to press a lever in a test cage to obtain alcohol or intravenous cocaine. Drug availability was paired with distinct olfactory, auditory, or visual stimuli. This phase was followed by extinction training, during which lever presses did not result in the presentation of the drug or the drug-associated stimuli. Extinction training led to a gradual decrease in the number of lever presses during test sessions. Relapse was triggered by presenting the rats with the drug-associated stimuli in the absence of alcohol or cocaine. The drug-associated stimuli were alone capable of inducing resumption of lever pressing and maintaining this behavior during repeated testing. The number of lever presses during a session represented the intensity of drug-seeking and relapse behavior. The results suggest that glutamatergic neurotransmission is involved in the modulation of drug-seeking behavior. Both alcohol and cocaine relapse were attenuated by systemic pretreatment with glutamate receptor antagonists. However, differences were found in the ability of ionotropic AMPA/kainate and NMDA receptor antagonists to regulate drug-seeking behavior. The AMPA/kainate antagonists CNQX and NBQX, and L-701,324, an antagonist with affinity for the glycine site of the NMDA receptor, attenuated cue-induced drug seeking, whereas the competitive NMDA antagonist CGP39551 and the NMDA channel blocker MK-801 were without effect. MPEP, an antagonist at metabotropic mGlu5 glutamate receptors, also decreased drug seeking, but its administration was found to lead to conditioned suppression of behavior during subsequent treatment sessions, suggesting that MPEP may have undesirable side effects. The mGluR2/3 agonist LY379268 and the mGluR8 agonist (S)-3,4-DCPG decreased both cue-induced relapse to alcohol drinking and alcohol consumption. Control experiments showed however that administration of the agonists was accompanied by motor suppression limiting their usefulness. Administration of the AMPA/kainate antagonist CNQX, the NMDA antagonist D-AP5, and the mGluR5 antagonist MPEP into the nucleus accumbens resulted also in a decrease in drug-seeking behavior, suggesting that the nucleus accumbens is at least one of the anatomical sites regulating drug seeking and mediating the effects of glutamate receptor antagonists on this behavior.

Photobiological studies of Baltic Sea phytoplankton

Phytoplankton ecology and productivity is one of the main branches of contemporary oceanographic research. Research groups in this branch have increasingly started to utilise bio-optical applications. My main research objective was to critically investigate the advantages and deficiencies of the fast repetition rate (FRR) fluorometry for studies of productivity of phytoplankton, and the responses of phytoplankton towards varying environmental stress. Second, I aimed to clarify the applicability of the FRR system to the optical environment of the Baltic Sea. The FRR system offers a highly dynamic tool for studies of phytoplankton photophysiology and productivity both in the field and in a controlled environment. The FRR metrics obtain high-frequency in situ determinations of the light-acclimative and photosynthetic parameters of intact phytoplankton communities. The measurement protocol is relatively easy to use without phases requiring analytical determinations. The most notable application of the FRR system lies in its potential for making primary productivity (PP) estimations. However, the realisation of this scheme is not straightforward. The FRR-PP, based on the photosynthetic electron flow (PEF) rate, are linearly related to the photosynthetic gas exchange (fixation of 14C) PP only in environments where the photosynthesis is light-limited. If the light limitation is not present, as is usually the case in the near-surface layers of the water column, the two PP approaches will deviate. The prompt response of the PEF rate to the short-term variability in the natural light field makes the field comparisons between the PEF-PP and the 14C-PP difficult to interpret, because this variability is averaged out in the 14C-incubations. Furthermore, the FRR based PP models are tuned to closely follow the vertical pattern of the underwater irradiance. Due to the photoacclimational plasticity of phytoplankton, this easily leads to overestimates of water column PP, if precautionary measures are not taken. Natural phytoplankton is subject to broad-waveband light. Active non-spectral bio-optical instruments, like the FRR fluorometer, emit light in a relatively narrow waveband, which by its nature does not represent the in situ light field. Thus, the spectrally-dependent parameters provided by the FRR system need to be spectrally scaled to the natural light field of the Baltic Sea. In general, the requirement of spectral scaling in the water bodies under terrestrial impact concerns all light-adaptive parameters provided by any active non-spectral bio-optical technique. The FRR system can be adopted to studies of all phytoplankton that possess efficient light harvesting in the waveband matching the bluish FRR excitation. Although these taxa cover the large bulk of all the phytoplankton taxa, one exception with a pronounced ecological significance is found in the Baltic Sea. The FRR system cannot be used to monitor the photophysiology of the cyanobacterial taxa harvesting light in the yellow-red waveband. These taxa include the ecologically-significant bloom-forming cyanobacterial taxa in the Baltic Sea.

Carbon balance and component CO2 fluxes in boreal Scots pine stands

The forest vegetation takes up atmospheric carbon dioxide (CO2) in photosynthesis. Part of the fixed carbon is released back into the atmosphere during plant respiration but a substantial part is stored as plant biomass, especially in the stems of trees. Carbon also accumulates in the soil as litter and via the roots. CO2 is released into the atmosphere from these carbon stocks in the decomposition of dead biomass. Carbon balance of a forest stand is the difference between the CO2 uptake and CO2 efflux. This study quantifies and analyses the dynamics of carbon balance and component CO2 fluxes in four Southern Finnish Scots pine stands that covered the typical economic rotation time of 80 years. The study was based on direct flux measurements with chambers and eddy covariance (EC), and modelling of component CO2 fluxes. The net CO2 exchange of the stand was partitioned into component fluxes: photosynthesis of trees and ground vegetation, respiration of tree foliage and stems, and CO2 efflux from the soil. The relationships between the component fluxes and the environmental factors (light, temperature, atmospheric CO2, air humidity and soil moisture) were studied with mathematical modelling. The annual CO2 balance varied from a source of about 400 g C/m2 at a recently clearcut site to net CO2 uptake of 200 300 g C/m2 in a middle-aged (40-year-old) and a mature (75-year-old) stand. A 12-year-old sapling site was at the turning point from source to a sink of CO2. In the middle-aged stand, photosynthetic production was dominated by trees. Under closed pine canopies, ground vegetation accounted for 10 20% of stand photosynthesis whereas at the open sites the proportion and also the absolute photosynthesis of ground vegetation was much higher. The aboveground respiration was dominated by tree foliage which accounted for one third of the ecosystem respiration. Rate of wood respiration was in the order of 10% of total ecosystem respiration. CO2 efflux from the soil dominated the ecosystem respiratory fluxes in all phases of stand development. Instantaneous and delayed responses to the environmental driving factors could predict well within-year variability in photosynthetic production: In the short term and during the growing season photosynthesis follows primarily light while the seasonal variation is more strongly connected to temperature. The temperature relationship of the annual cycle of photosynthesis was found to be almost equal in the southern boreal zone and at the timberline in the northern boreal zone. The respiratory fluxes showed instantaneous and seasonal temperature relationships but they could also be connected to photosynthesis at an annual timescale.

Plant guard cell anion channel SLAC1 regulates stomatal closure

Plants are rooted to their growth place; therefore it is important that they react adequately to changes in environmental conditions. Stomatal pores, which are formed of a pair of guard cells in leaf epidermis, regulate plant gas-exchange. Importantly, guard cells protect the plant from desiccation in drought conditions by reducing the aperture of the stomatal pore. They serve also as the first barrier against the major air pollutant ozone, but the behaviour of guard cells during ozone exposure has not been sufficiently addressed. Aperture of the stomatal pore is regulated by the influx and efflux of osmotically active ions via ion channels and transporters across the guard cell membrane, however the molecular identity of guard cell plasma membrane anion channel has remained unknown. In the frame of this study, guard cell behaviour during ozone exposure was studied using the newly constructed Arabidopsis whole-rosette gas-exchange system. Ozone induced a Rapid Transient Decrease (RTD) in stomatal conductance within 10 min from the start of exposure, which was followed by a recovery in the conductance within the next 40 min. The decrease in stomatal conductance was dependent on the applied ozone concentration. Three minutes of ozone exposure was sufficient to induce RTD and further ozone application during the closure-recovery process had no effect on RTD, demonstrating that the whole process is programmed within the first three minutes. To address the molecular components responsible for RTD, the ozone response was measured in 59 different Arabidopsis mutants involved in guard cell signalling. Four of the tested mutants slac1 (originally rcd3), ost1, abi1-1 and abi2-1 lacked RTD completely. As the ozone sensitive mutant slac1 lacked RTD, the next aim of this study was to identify and characterize SLAC1. SLAC1 was shown to be a central regulator in response to all major factors regulating guard cell aperture: CO2, light/darkness transitions, ozone, relative air humidity, ABA, NO, H2O2, and extracellular Ca2+. It encodes the first guard cell plasma membrane slow type anion channel to be identified at the molecular level. Interestingly, the rapid type anion conductance was intact in slac1 mutant plants. For activation, SLAC1 needs to be phosphorylated. Protein kinase OST1 was shown to phosphorylate several amino acids in the N-terminal tail of SLAC1, Ser120 was one of its main targets, which led to SLAC1 activation. The lack of RTD in type 2C protein phosphatase mutants abi1-1 and abi2-1, suggests that these proteins have a regulatory role in ozoneinduced activation of the slow type anion channel.

Phytoplankton ecology of subarctic lakes in Finnish Lapland

Climate is warming and it is especially seen in arctic areas, where the warming trend is expected to be greatest. Arctic freshwater ecosystems, which are a very characteristic feature of the arctic landscape, are especially sensitive to climate change. They could be used as early warning systems, but more information about the ecosystem functioning and responses are needed for proper interpretation of the observations. Phytoplankton species and assemblages could be especially suitable for climate-related studies, since they have short generation times and react rapidly to changes in the environment. In addition, phytoplankton provides a good tool for lake classifications, since different species have different requirements and tolerance ranges for various environmental factors. The use of biological indicators is especially useful in arctic areas, were many of the chemical factors commonly fall under the detection limit and therefore do not provide much information about the environment. This work brings new information about species distribution and dynamics of arctic freshwater phytoplankton in relation to environmental factors. The phytoplankton of lakes in Finnish Lapland and other European high-altitude or high-latitude areas were compared. Most lakes were oligotrophic and dominated by flagellated species belonging to chrysophytes, cryptophytes and dinoflagellates. In Finnish Lapland cryptophytes were of less importance, whereas desmids had high species richness in many of the lakes. In Pan-European scale, geographical and catchment-related factors were explaining most of the differences in species distributions between different districts, whereas lake water chemistry (especially conductivity, SiO2 and pH) was most important regionally. Seasonal and interannual variation of phytoplankton was studied in subarctic Lake Saanajärvi. Characteristic phytoplankton species in this oligotrophic, dimictic lake belonged mainly to chrysophytes and diatoms. The maximum phytoplankton biomass in Lake Saanajärvi occurs during autumn, while spring biomass is very low. During years with heavy snow cover the lake suffers from pH drop caused by melt waters, but the effects of this acid pulse are restricted to surface layers and last for a relatively short period. In addition to some chemical parameters (mainly Ca and nutrients), length of the mixing cycle and physical factors such as lake water temperature and thermal stability of water column had major impact on phytoplankton dynamics. During a year with long and strong thermal stability, the phytoplankton community developed towards an equilibrium state, with heavy dominance of only a few taxa for a longer period of time. During a year with higher windiness and less thermal stability, the species composition was more diverse and species with different functional strategies were able to occur simultaneously. The results of this work indicate that although arctic lakes in general share many common features concerning their catchment and water chemistry, large differences in biological features can be found even in a relatively small area. Most likely the lakes with very different algal flora do not respond in a similar way to differences in the environmental factors, and more information about specific arctic lake types is needed. The results also show considerable year to year differences in phytoplankton species distribution and dynamics, and these changes are most likely linked to climatic factors.

Multiwavelength studies of regolith effects in planetary remote sensing

A large proportion of our knowledge about the surfaces of atmosphereless solar-system bodies is obtained through remote-sensing measurements. The measurements can be carried out either as ground-based telescopic observations or space-based observations from orbiting spacecraft. In both cases, the measurement geometry normally varies during the observations due to the orbital motion of the target body, the spacecraft, etc.. As a result, the data are acquired over a variety of viewing and illumination angles. Surfaces of planetary bodies are usually covered with a layer of loose, broken-up rock material called the regolith whose physical properties affect the directional dependence of remote-sensed measurements. It is of utmost importance for correct interpretation of the remote-sensed data to understand the processes behind this alteration. In the thesis, the multi-angular effects that the physical properties of the regolith have on remote-sensing measurements are studied in two regimes of electromagnetic radiation, visible to near infrared and soft X-rays. These effects are here termed generally the regolith effects in remote sensing. Although the physical mechanisms that are important in these regions are largely different, notable similarities arise in the methodology that is used in the study of the regolith effects, including the characterization of the regolith both in experimental studies and in numerical simulations. Several novel experimental setups have been constructed for the thesis. Alongside the experimental work, theoretical modelling has been carried out, and results from both approaches are presented. Modelling of the directional behaviour of light scattered from a regolith is utilized to obtain shape and spin-state information of several asteroids from telescopic observations and to assess the surface roughness and single-scattering properties of lunar maria from spacecraft observations. One of the main conclusions is that the azimuthal direction is an important factor in detailed studies of planetary surfaces. In addition, even a single parameter, such as porosity, can alter the light scattering properties of a regolith significantly. Surface roughness of the regolith is found to alter the elemental fluorescence line ratios of a surface obtained through planetary soft X-ray spectrometry. The results presented in the thesis are among the first to report this phenomenon. Regolith effects need to be taken into account in the analysis of remote-sensed data, providing opportunities for retrieving physical parameters of the surface through inverse methods.

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.

Teille on syntynyt Vapahtaja : Joulun kirkollinen sanoma, jouluperinteet ja perheyhteisö Yleisradion TV-jumalanpalvelusten joulusaarnoissa 1985 - 2009

Yleisradion jouluaamuna lähettämä TV-jumalanpalvelus kerää vuosittain enemmän katsojia kuin kaikissa Suomen kirkoissa yhteensä käy ihmisiä samana aamuna. TV:n joulusaarnalla onkin merkitystä siihen, miten ihmiset mieltävät kirkon sanoman joulusta. Tämän tutkimuksen tarkoituksena oli tarkastella TV-jumalanpalveluksen joulusaarnan muutosta vuosien 1985 ja 2009 välisenä aikana sekä toteutuksen että sisällön näkökulmasta. Pääasiallisena tutkimuskohteena oli sisällön muutos (1) kirkollisen sanoman, (2) jouluperinteen ja -tunnelman sekä (3) perheyhteisön kuvausten suhteen. Teemat valittiin aiempien saarnatutkimusten sekä kolmen joulusaarnan alustavan analyysin perusteella. Tutkimusaineiston muodostivat kaikki Kirkon tiedotuskeskuksen arkistosta löytyneet joulusaarnat, joissa oli sekä kuva että ääni. Aineisto koostui 20 saarnasta, jotka litteroitiin ja analysoitiin. Lisäksi nauhoitettiin kaksi taustahaastattelua. Tutkimusmetodina käytettiin kvalitatiivista metodia, teoriaohjaavaa sisällönanalyysiä, jonka tulokset luokiteltiin ja kvantifioitiin. Sisällönanalyysin tuloksia havainnollistettiin taulukoiden ja graafisten kuvioiden avulla. Muutoksen havaitsemisen apuna käytettiin summamuuttujia neljän tarkastelujakson osalta, vuosilta 1985-1991, 1992-1996, 2000-2004 ja 2005-2009. Saarnojen toteutuksen suhteen todettiin, että joulusaarnat lyhentyivät hieman tutkimusjakson aikana. Saarnan kuvitus muuttui vuodesta 2003 lähtien niukemmaksi, jotta katsojat voisivat keskittyä paremmin saarnan sisältöön. Saarnaajien oheisviestintä oli vähäistä, ja useimmiten saarnaajilla oli vain yksi ilme ja erittäin vähän eleitä. Kertomusten käyttö lisääntyi saarnoissa selvästi, ja vuosina 2005-2009 sekä jouluevankeliumia että muita raamatunkohtia havainnollistettiin kertomusten avulla aiempaa enemmän. Yleisin saarnoissa lainattu raamatunkohta oli enkelien julistus ”Teille on syntynyt Vapahtaja” . Jeesukseen viittaavat nimitykset muuttuivat tutkimusjakson aikana mielenkiintoisella tavalla. Nimike Jeesus oli yleisin nimike vuodesta 1985 vuoteen 2004. Sen jälkeen yleisimmäksi nimikkeeksi nousi lapsi, ja joulusaarnoissa käytettiin runsaasti myös muita yleiskieleen kuuluvia nimikkeitä, jotka tiivistettiin muotoon avuton lapsi/vastasyntynyt. Perinteisiä kristillisiä nimikkeitä, kuten Herra, Kristus ja seimen lapsi, ei käytetty vuosina 2005-2009 lainkaan. Tämä herätti kysymyksen siitä, onko joulun sanoma maallistunut. Oletus ei saanut tukea kirkolliseen sanomaan liittyvien teemojen tarkastelusta. Vaikka syyllisyyden kuvaukset vähentyivät, rakkauden merkitys korostui tutkimusjakson loppua kohden, ja myös elämän tarkoitukseen liittyvät asiat mainittiin 2000-luvulla useammin kuin aiemmin. Erityisesti inkarnaation Jumalan ihmiseksi tulemisen kuvaukset lisääntyivät, joten joulun kirkollinen ydinsanoma oli entistä selkeämmin esillä. Jouluperinteen kuvausten suhteen ei havaittu muutosta vuosikymmenten aikana. Tunnelmaa kuvattiin tutkimusjakson alussa rauhan ja ihmeen käsittein, mutta lopussa valo korostui. Perheyhteisön kuvaukset olivat hyvin esillä, sillä lapset mainittiin joka toisessa ja perhe joka kolmannessa saarnassa. Lapset mainittiin vuosikymmenten kuluessa entistä useammin, ja myös yksinäisyyden kuvaukset lisääntyivät. Seurakunta mainittiin joulusaarnoissa hyvin harvoin, mikä sai pohtimaan seurakunnan roolia yhteisöllisyyden kannalta. Tutkimuksen johtopäätöksenä todettiin, että suomalaisen nyky-yhteiskunnan maallistumiskehitys ei näy TV:n joulusaarnoissa 1985-2009.

Tablettien soveltuvuus annosjakeluun

Koneellinen annosjakelu on kasvava lääkehuollon osa-alue, jossa lääkkeet pakataan koneellisesti pieniin annoskertakohtaisiin pusseihin kahden viikon erissä. Aikaisemmin lääkevalmisteiden soveltuvuutta koneelliseen annosjakeluun ei ole systemaattisesti tutkittu. Tutkimus tehtiin yhteistyössä Espoonlahden apteekin annosjakeluyksikön kanssa ja sen tavoitteena oli määrittää annosjakeluprosessin kannalta optimaaliset ominaisuudet annosjaeltavalle tabletille rikkoutumisten ja siirtymien vähentämiseksi. Rikkoutuminen on lääkevalmisteen murentumista, puolittumista tai muuta rikkoutumista annosjakelun aikana. Siirtymä on lääkevalmisteen jakelu väärään annospussiin. Prosentuaalisesti rikkoutumisia ja siirtymiä on jakelumäärästä hyvin vähän, mutta määrällisesti paljon ja koko ajan enemmän koneellisen annosjakelun yleistyessä. Rikkoutumiset ja siirtymät aiheuttavat paljon lisätyötä pussien korjaamisen takia, joten niiden määrää on pyrittävä vähentämään. Lisäksi tavoitteena oli selvittää lääkkeiden valmistajilta kysyttävissä olevat asiat lääkevalmisteiden ominaisuuksista ja säilyvyydestä, jotta voitaisiin päätellä valmisteen soveltuvuus koneelliseen annosjakeluun kirjallisen tiedon perusteella. Tutkimuksen tulosten perusteella rikkoutumisten ja siirtymien vähentämiseksi optimaalinen tablettivalmiste annosjakeluun on pienehkö tai keskisuuri, päällystetty, luja ja jakouurteeton ja optimaalinen ilman suhteellinen kosteustaso annosjakeluyksikön tuotantotiloissa olisi noin 30 – 40 %. Lääkkeiden valmistajilta kysyttäviä seikkoja ovat koon, päällysteen, murtolujuuden ja jakouurteen lisäksi valmisteen säilyvyys alkuperäispakkauksen ulkopuolella sekä valmisteen valo-, lämpö- ja kosteusherkkyys. Rikkoutumisten ja siirtymien lisäksi tutkittiin myös kosteusherkän asetyylisalisyylihappovalmisteen (Disperin 100 mg) säilyvyyttä 25 °C ja 60 % RH olosuhteissa, koska tuotantotilojen ilman kosteustasoa ei ole säädelty. Säilyvyystutkimuksen kesto oli neljä viikkoa. Se on riittävä, koska se on enimmäisaika, jonka tabletit ovat annosjakeluprosessin yhteydessä pois alkuperäispakkauksestaan ennen käyttöä. Tabletteja säilytettiin avoimessa alkuperäispakkauksessa (purkki), suljetussa alkuperäispakkauksessa, annosjakelukoneen kasetissa ja kahdessa erilaisessa annospussissa (uusi ja käytössä oleva materiaali). Tulosten mukaan annosjakelukoneen kasetti suojaa kosteudelta yhtä huonosti kuin avoin purkki. Uusi pussimateriaali sen sijaan suojaa kosteudelta paremmin kuin tällä hetkellä käytössä oleva materiaali. Raman -spektroskopiamittausten perusteella asetyylisalisyylihappotableteissa ei ehdi neljän viikon seurannan aikana tapahtua asetyylisalisyylihapon hajoamista salisyylihapoksi. Kosteus heikentää tablettien murtolujuutta, mikä saattaa aiheuttaa enemmän rikkoutumisia. Kosteustaso olisi hyvä olla säädettävissä vakioksi tuotantotiloissa tai purkaa tabletit kasetteihin mahdollisimman lähellä jakelua rikkoutumisten ehkäisemiseksi, etenkin ilman kosteustason ollessa korkea. Lisäksi tutkittiin lääkevalmisteen lämpöherkkyyttä koska annosjakelukoneen saumauslaite altistaa annospussit noin 75 °C lämmölle, jos annosjakelukone pysäytetään kesken työn. Tutkimus tehtiin XRPD:llä, jolla voidaan säätää näytteen lämpötilaa. Lämpöherkkyystutkimusten perusteella 75 °C lämpö ei ehdi tunnin aikana aiheuttaa muutoksia karbamatsepiinitabletissa (Neurotol 200 mg). Tuloksista selvisi, että tutkitun valmisteen sisältämä karbamatsepiini ei kuitenkaan ole lämpöherkin muoto, joten muita lämpöherkkiä lääkevalmisteita tulisi tutkia lisätiedon saamiseksi lämmön vaikutuksista.