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.

Pyhä Kolminaisuus vai pilven reunalla istuva partasuu? : Jumalakuva evankelisluterilaisissa ja ortodoksissa 1.–4.-luokan uskonnon oppikirjoissa 1970–80- ja 2000-luvuilla

A concept of god is a wholeness that an individual experiences as God. The Christian concept of god is based on triune God: Father, Son, and the Holy Spirit. The concept of god is examined in different kinds of contexts particularly between the 1940's and the 1970's. Many researches of school books have widely been made in Finland, but, however, only a few from the point of view of the concept of god. Considering this, the concept of god in the school books of Evangelical Lutheran and Orthodox religion from first to fourth grade in 1970–80 and 2000 is examined in this survey. Additionally, the concept of god in curricula between years 1970 and 2004 is studied. The perspective on the concept of god is the change in the course of time and denominational emphasis. As a first hypothesis, God the Father is represented in books in 21st century as a kind and loving figure. As a second hypothesis, the Trinity and the Holy Spirit get more space in Orthodox books comparing with the Lutheran books. Twelve school books of Evangelical Lutheran and Orthodox religion from first to fourth grade were used as a research material. The books were from four different series between the years 1978 and 2005. Teacher's guidebooks and student's exercise books were left outside of this survey. The research material was analyzed by using abductive content analysis and methodological triangulation. This study included both qualitative and quantitative aspects. The classification system which defined the classifying of concept of god from the research material was consisted of the basis of research material, former reseach, and subtext of used theories. The number of mentions in concept of god was higher in books from the 21st century. In Lutheran books, the change was seen as a growth of the category of God the Father. In Orthodox books, the trend was opposite: the category of Jesus the Son had grown. Differing from the presupposition, the features of loving God in new books had less emphasis than in older books in both churces. The mentions of the Holy Spirit and Trinity were marginal. In the Orthodox books, the categories were bigger, as it was presupposed. It could be seen, that the books confirmed the legalistic period of the concept of god on 3rd and 4th grades. The mentions of concept of god in curriculas have diminished and generalized. The diminution was seen most radically in the curriculum from the year 1994. The results tell something about social changes and views of innovation in curricula. In books the change was not perceived that bright. The idea of the concept of god getting shrank and decreased during the time can be refused.

Burnt area mapping in insular Southeast Asia using medium resolution satellite imagery

Burnt area mapping in humid tropical insular Southeast Asia using medium resolution (250-500m) satellite imagery is characterized by persisting cloud cover, wide range of land cover types, vast amount of wetland areas and highly varying fire regimes. The objective of this study was to deepen understanding of three major aspects affecting the implementation and limits of medium resolution burnt area mapping in insular Southeast Asia: 1) fire-induced spectral changes, 2) most suitable multitemporal compositing methods and 3) burn scars patterns and size distribution. The results revealed a high variation in fire-induced spectral changes depending on the pre-fire greenness of burnt area. It was concluded that this variation needs to be taken into account in change detection based burnt area mapping algorithms in order to maximize the potential of medium resolution satellite data. Minimum near infrared (MODIS band 2, 0.86μm) compositing method was found to be the most suitable for burnt area mapping purposes using Moderate Resolution Imaging Spectroradiometer (MODIS) data. In general, medium resolution burnt area mapping was found to be usable in the wetlands of insular Southeast Asia, whereas in other areas the usability was seriously jeopardized by the small size of burn scars. The suitability of medium resolution data for burnt area mapping in wetlands is important since recently Southeast Asian wetlands have become a major point of interest in many fields of science due to yearly occurring wild fires that not only degrade these unique ecosystems but also create regional haze problem and release globally significant amounts of carbon into the atmosphere due to burning peat. Finally, super-resolution MODIS images were tested but the test failed to improve the detection of small scars. Therefore, super-resolution technique was not considered to be applicable to regional level burnt area mapping in insular Southeast Asia.

Aerosol size distribution and its connection to cloud droplet number concentration

In order to predict the current state and future development of Earth s climate, detailed information on atmospheric aerosols and aerosol-cloud-interactions is required. Furthermore, these interactions need to be expressed in such a way that they can be represented in large-scale climate models. The largest uncertainties in the estimate of radiative forcing on the present day climate are related to the direct and indirect effects of aerosol. In this work aerosol properties were studied at Pallas and Utö in Finland, and at Mount Waliguan in Western China. Approximately two years of data from each site were analyzed. In addition to this, data from two intensive measurement campaigns at Pallas were used. The measurements at Mount Waliguan were the first long term aerosol particle number concentration and size distribution measurements conducted in this region. They revealed that the number concentration of aerosol particles at Mount Waliguan were much higher than those measured at similar altitudes in other parts of the world. The particles were concentrated in the Aitken size range indicating that they were produced within a couple of days prior to reaching the site, rather than being transported over thousands of kilometers. Aerosol partitioning between cloud droplets and cloud interstitial particles was studied at Pallas during the two measurement campaigns, First Pallas Cloud Experiment (First PaCE) and Second Pallas Cloud Experiment (Second PaCE). The method of using two differential mobility particle sizers (DMPS) to calculate the number concentration of activated particles was found to agree well with direct measurements of cloud droplet. Several parameters important in cloud droplet activation were found to depend strongly on the air mass history. The effects of these parameters partially cancelled out each other. Aerosol number-to-volume concentration ratio was studied at all three sites using data sets with long time-series. The ratio was found to vary more than in earlier studies, but less than either aerosol particle number concentration or volume concentration alone. Both air mass dependency and seasonal pattern were found at Pallas and Utö, but only seasonal pattern at Mount Waliguan. The number-to-volume concentration ratio was found to follow the seasonal temperature pattern well at all three sites. A new parameterization for partitioning between cloud droplets and cloud interstitial particles was developed. The parameterization uses aerosol particle number-to-volume concentration ratio and aerosol particle volume concentration as the only information on the aerosol number and size distribution. The new parameterization is computationally more efficient than the more detailed parameterizations currently in use, but the accuracy of the new parameterization was slightly lower. The new parameterization was also compared to directly observed cloud droplet number concentration data, and a good agreement was found.

On measurements of formation, growth, hygroscopicity, and volatility of atmospheric ultrafine particles

Atmospheric aerosol particles affect the global climate as well as human health. In this thesis, formation of nanometer sized atmospheric aerosol particles and their subsequent growth was observed to occur all around the world. Typical formation rate of 3 nm particles at varied from 0.01 to 10 cm-3s-1. One order of magnitude higher formation rates were detected in urban environment. Highest formation rates up to 105 cm-3s-1 were detected in coastal areas and in industrial pollution plumes. Subsequent growth rates varied from 0.01 to 20 nm h-1. Smallest growth rates were observed in polar areas and the largest in the polluted urban environment. This was probably due to competition between growth by condensation and loss by coagulation. Observed growth rates were used in the calculation of a proxy condensable vapour concentration and its source rate in vastly different environments from pristine Antarctica to polluted India. Estimated concentrations varied only 2 orders of magnitude, but the source rates for the vapours varied up to 4 orders of magnitude. Highest source rates were in New Delhi and lowest were in the Antarctica. Indirect methods were applied to study the growth of freshly formed particles in the atmosphere. Also a newly developed Water Condensation Particle Counter, TSI 3785, was found to be a potential candidate to detect water solubility and thus indirectly composition of atmospheric ultra-fine particles. Based on indirect methods, the relative roles of sulphuric acid, non-volatile material and coagulation were investigated in rural Melpitz, Germany. Condensation of non-volatile material explained 20-40% and sulphuric acid the most of the remaining growth up to a point, when nucleation mode reached 10 to 20 nm in diameter. Coagulation contributed typically less than 5%. Furthermore, hygroscopicity measurements were applied to detect the contribution of water soluble and insoluble components in Athens. During more polluted days, the water soluble components contributed more to the growth. During less anthropogenic influence, non-soluble compounds explained a larger fraction of the growth. In addition, long range transport to a measurement station in Finland in a relatively polluted air mass was found to affect the hygroscopicity of the particles. This aging could have implications to cloud formation far away from the pollution sources.

Agricultural expansion and climate change in the Taita Hills, Kenya: an assessment of potential environmental impacts

The indigenous cloud forests in the Taita Hills have suffered substantial degradation for several centuries due to agricultural expansion. Currently, only 1% of the original forested area remains preserved in this region. Furthermore, climate change imposes an imminent threat for local economy and environmental sustainability. In such circumstances, elaborating tools to conciliate socioeconomic growth and natural resources conservation is an enormous challenge. This dissertation tackles essential aspects for understanding the ongoing agricultural activities in the Taita Hills and their potential environmental consequences in the future. Initially, alternative methods were designed to improve our understanding of the ongoing agricultural activities. Namely, methods for agricultural survey planning and to estimate evapotranspiration were evaluated, taking into account a number of limitations regarding data and resources availability. Next, this dissertation evaluates how upcoming agricultural expansion, together with climate change, will affect the natural resources in the Taita Hills up to the year 2030. The driving forces of agricultural expansion in the region were identified as aiming to delineate future landscape scenarios and evaluate potential impacts from the soil and water conservation point of view. In order to investigate these issues and answer the research questions, this dissertation combined state of the art modelling tools with renowned statistical methods. The results indicate that, if current trends persist, agricultural areas will occupy roughly 60% of the study area by 2030. Although the simulated land use changes will certainly increase soil erosion figures, new croplands are likely to come up predominantly in the lowlands, which comprise areas with lower soil erosion potential. By 2030, rainfall erosivity is likely to increase during April and November due to climate change. Finally, this thesis addressed the potential impacts of agricultural expansion and climate changes on Irrigation Water Requirements (IWR), which is considered another major issue in the context of the relations between land use and climate. Although the simulations indicate that climate change will likely increase annual volumes of rainfall during the following decades, IWR will continue to increase due to agricultural expansion. By 2030, new cropland areas may cause an increase of approximately 40% in the annual volume of water necessary for irrigation.

Accumulation of point mutations and reassortment of genomic RNA segments are involved in the microevolution of Puumala hantavirus in a bank vole (Myodes glareolus) population

"The genetic diversity of Puumala hantavirus (PUUV) was studied in a local population of its natural host, the bank vole (Myodes glareolus). The trapping area (2.5x2.5 km) at Konnevesi, Central Finland, included 14 trapping sites, at least 500 m apart; altogether, 147 voles were captured during May and October 2005. Partial sequences of the S, M and L viral genome segments were recovered from 40 animals. Seven, 12 and 17 variants were detected for the S, M and L sequences, respectively; these represent new wild-type PUUV strains that belong to the Finnish genetic lineage. The genetic diversity of PUUV strains from Konnevesi was 0.2-4.9% for the S segment, 0.2-4.8% for the M segment and 0.2-9.7% for the L segment. Most nucleotide substitutions were synonymous and most deduced amino acid substitutions were conservative, probably due to strong stabilizing selection operating at the protein level. Based on both sequence markers and phylogenetic clustering, the S, M and L sequences could be assigned to two groups, 'A' and 'B'. Notably, not all bank voles carried S, M and L sequences belonging to the same group, i.e. SAMALA or SBMBLB.. A substantial proportion (8/40, 20%) of the newly characterized PUUV strains possessed reassortant genomes such as SBMALA, SAMBLB or SBMALB. These results suggest that at least some of the PUUV reassortants are viable and can survive in the presence of their parental strains."

A Hub System for Cloud-Computing Based Business-Collaboration: Automating Ontology-Enabled Electronic Business-Service Discovery

The management and coordination of business-process collaboration experiences changes because of globalization, specialization, and innovation. Service-oriented computing (SOC) is a means towards businessprocess automation and recently, many industry standards emerged to become part of the service-oriented architecture (SOA) stack. In a globalized world, organizations face new challenges for setting up and carrying out collaborations in semi-automating ecosystems for business services. For being efficient and effective, many companies express their services electronically in what we term business-process as a service (BPaaS). Companies then source BPaaS on the fly from third parties if they are not able to create all service-value inhouse because of reasons such as lack of reasoures, lack of know-how, cost- and time-reduction needs. Thus, a need emerges for BPaaS-HUBs that not only store service offers and requests together with information about their issuing organizations and assigned owners, but that also allow an evaluation of trust and reputation in an anonymized electronic service marketplace. In this paper, we analyze the requirements, design architecture and system behavior of such a BPaaS-HUB to enable a fast setup and enactment of business-process collaboration. Moving into a cloud-computing setting, the results of this paper allow system designers to quickly evaluate which services they need for instantiationg the BPaaS-HUB architecture. Furthermore, the results also show what the protocol of a backbone service bus is that allows a communication between services that implement the BPaaS-HUB. Finally, the paper analyzes where an instantiation must assign additional computing resources vor the avoidance of performance bottlenecks.