Relative Contribution of Cell Proliferation and Microvascularity to Metastasis in Malignant Uveal Melanoma

Uveal melanoma (UM) is the second most common primary intraocular cancer worldwide. It is a relatively rare cancer, but still the second most common type of primary malignant melanoma in humans. UM is a slowly growing tumor, and gives rise to distant metastasis mainly to the liver via the bloodstream. About 40% of patients with UM die of metastatic disease within 10 years of diagnosis, irrespective of the type of treatment. During the last decade, two main lines of research have aimed to achieve enhanced understanding of the metastasis process and accurate prognosis of patients with UM. One emphasizes the characteristics of tumor cells, particularly their nucleoli, and markers of proliferation, and the other the characteristics of tumor blood vessels. Of several morphometric measurements, the mean diameter of the ten largest nucleoli (MLN) has become the most widely applied. A large MLN has consistently been associated with high likelihood of dying from UM. Blood vessels are of paramount importance in metastasis of UM. Different extravascular matrix patterns can be seen in UM, like loops and networks. This presence is associated with death from metastatic melanoma. However, the density of microvessels is also of prognostic importance. This study was undertaken to help understanding some histopathological factors which might contribute to developing metastasis in UM patients. Factors which could be related to tumor progression to metastasis disease, namely nucleolar size, MLN, microvascular density (MVD), cell proliferation, and The Insulin-like Growth Factor 1 Receptor(IGF-1R), were investigated. The primary aim of this thesis was to study the relationship between prognostic factors such as tumor cell nucleolar size, proliferation, extravascular matrix patterns, and dissemination of UM, and to assess to what extent there is a relationship to metastasis. The secondary goal was to develop a multivariate model which includes MLN and cell proliferation in addition to MVD, and which would fit better with population-based, melanoma-related survival data than previous models. I studied 167 patients with UM, who developed metastasis even after a very long time following removal of the eye, metastatic disease was the main cause of death, as documented in the Finnish Cancer Registry and on death certificates. Using an independent population-based data set, it was confirmed that MLN and extravascular matrix loops and networks were unrelated, independent predictors of survival in UM. Also, it has been found that multivariate models including MVD in addition to MLN fitted significantly better with survival data than models which excluded MVD. This supports the idea that both the characteristics of the blood vessels and the cells are important, and the future direction would be to look for the gene expression profile, whether it is associated more with MVD or MLN. The former relates to the host response to the tumor and may not be as tightly associated with the gene expression profile, yet most likely involved in the process of hematogenous metastasis. Because fresh tumor material is needed for reliable genetic analysis, such analysis could not be performed Although noninvasive detection of certain extravascular matrix patterns is now technically possible,in managing patients with UM, this study and tumor genetics suggest that such noninvasive methods will not fully capture the process of clinical metastasis. Progress in resection and biopsy techniques is likely in the near future to result in fresh material for the ophthalmic pathologist to correlate angiographic data, histopathological characteristics such as MLN, and genetic data. This study supported the theory that tumors containing epithelioid cells grow faster and have poorer prognosis when studied by cell proliferation in UM based on Ki-67 immunoreactivity. Cell proliferation index fitted best with the survival data when combined with MVD, MLN, and presence of epithelioid cells. Analogous with the finding that high MVD in primary UM is associated with shorter time to metastasis than low MVD, high MVD in hepatic metastasis tends to be associated with shorter survival after diagnosis of metastasis. Because the liver is the main organ for metastasis from UM, growth factors largely produced in the liver hepatocyte growth factor, epidermal growth factor and insulin-like growth factor-1 (IGF-1) together with their receptors may have a role in the homing and survival of metastatic cells. Therefore the association between immunoreactivity for IGF-1R in primary UM and metastatic death was studied. It was found that immunoreactivity for IGF-IR did not independently predict metastasis from primary UM in my series.

A new method for modulating the activity of parvalbumin-positive neurons and cerebellar Purkinje cells in vivo

Neurons can be divided into various classes according to their location, morphology, neurochemical identity and electrical properties. They form complex interconnected networks with precise roles for each cell type. GABAergic neurons expressing the calcium-binding protein parvalbumin (Pv) are mainly interneurons, which serve a coordinating function. Pv-cells modulate the activity of principal cells with high temporal precision. Abnormalities of Pv-interneuron activity in cortical areas have been linked to neuropsychiatric illnesses such as schizophrenia. Cerebellar Purkinje cells are known to be central to motor learning. They are the sole output from the layered cerebellar cortex to deep cerebellar nuclei. There are still many open questions about the precise role of Pv-neurons and Purkinje cells, many of which could be answered if one could achieve rapid, reversible cell-type specific modulation of the activity of these neurons and observe the subsequent changes at the whole-animal level. The aim of these studies was to develop a novel method for the modulation of Pv-neurons and Purkinje cells in vivo and to use this method to investigate the significance of inhibition in these neuronal types with a variety of behavioral experiments in addition to tissue autoradiography, electrophysiology and immunohistochemistry. The GABA(A) receptor γ2 subunit was ablated from Pv-neurons and Purkinje cells in four separate mouse lines. Pv-Δγ2 mice had wide-ranging behavioral alterations and increased GABA-insensitive binding indicative of an altered GABA(A) receptor composition, particularly in midbrain areas. PC-Δγ2 mice experienced little or no motor impairment despite the lack of inhibition in Purkinje cells. In Pv-Δγ2-partial rescue mice, a reversal of motor and cognitive deficits was observed in addition to restoration of the wild-type γ2F77 subunit to the reticular nucleus of thalamus and the cerebellar molecular layer. In PC-Δγ2-swap mice, zolpidem sensitivity was restored to Purkinje cells and the administration of systemic zolpidem evoked a transient motor impairment. On the basis of these results, it is concluded that this new method of cell-type specific modulation is a feasible way to modulate the activity of selected neuronal types. The importance of Purkinje cells to motor control supports previous studies, and the crucial involvement of Pv-neurons in a range of behavioral modalities is confirmed.

Seismic response of a long span cable

The dynamic response of a single span cable due to a travelling seismic excitation is studied in this paper. The influence of propagation time between the supports is investigated in detail. The importance of considering both vertical and longitudinal equations of motion in the analysis is highlighted. The results indicate the considerable influence of the time-lagged support motions on the cable dynamic tension. A modal combination rule based on the response spectrum method is developed to arrive at the peak estimates of the cable response. Some significant aspects of cable behaviour, especially under horizontal support motion, are discussed.

HDL subspecies : association with low HDL-C, obesity, and metabolic syndrome

AIMS An independent, powerful coronary heart disease (CHD) predictor is a low level of high-density lipoprotein cholesterol (HDL-C). Discoidal preβ-HDL particles and large HDL2 particles are the primary cholesterol acceptors in reverse cholesterol transport, a key anti-atherogenic HDL mechanism. The quality of HDL subspecies may provide better markers of HDL functionality than does HDL-C alone. We aimed I) to study whether alterations in the HDL subspecies profile exist in low-HDL-C subjects II) to explore the relationship of any changes in HDL subspecies profile in relation to atherosclerosis and metabolic syndrome; III) to elucidate the impact of genetics and acquired obesity on HDL subspecies distribution. SUBJECTS The study consisted of 3 cohorts: A) Finnish families with low HDL-C and premature CHD (Study I: 67 subjects with familial low HDL-C and 64 controls; Study II: 83 subjects with familial low HDL-C, 65 family members with normal HDL-C, and 133 controls); B) a cohort of 113 low- and 133 high-HDL-C subjects from the Health 2000 Health Examination Survey carried out in Finland (Study III); and C) a Finnish cohort of healthy young adult twins (52 monozygotic and 89 dizygotic pairs) (Study IV). RESULTS AND CONCLUSIONS The subjects with familial low HDL-C had a lower preβ-HDL concentration than did controls, and the low-HDL-C subjects displayed a dramatic reduction (50-70%) in the proportion of large HDL2b particles. The subjects with familial low HDL-C had increased carotid atherosclerosis measured as intima-media-thickness (IMT), and HDL2b particles correlated negatively with IMT. The reduction in both key cholesterol acceptors, preβ-HDL and HDL2 particles, supports the concept of impaired reverse cholesterol transport contributing to the higher CHD risk in low-HDL-C subjects. The family members with normal HDL-C and the young adult twins with acquired obesity showed a reduction in large HDL2 particles and an increase in small HDL3 particles, which may be the first changes leading to the lowering of HDL-C. The low-HDL-C subjects had a higher serum apolipoprotein E (apoE) concentration, which correlated positively with the metabolic syndrome components (waist circumference, TG, and glucose), highlighting the need for a better understanding of apoE metabolism in human atherosclerosis. In the twin study, the increase in small HDL3b particles was associated with obesity independent of genetic effects. The heritability estimate, of 73% for HDL-C and 46 to 63% for HDL subspecies, however, demonstrated a strong genetic influence. These results suggest that the relationship between obesity and lipoproteins depends on different elements in each subject. Finally, instead of merely elevating HDL-C, large HDL2 particles and discoidal preβ-HDL particles may provide beneficial targets for HDL-targeted therapy.

Kehittämistutkimus: Tieto- ja viestintätekniikkaa kemian opetukseen

The main aim of the present study was to develop information and communication technology (ICT) based chemistry education. The goals for the study were to support meaningful chemistry learning, research-based teaching and diffusion of ICT innovations. These goals were used as guidelines that form the theoretical framework for this study. This Doctoral Dissertation is based on eight-stage research project that included three design researches. These three design researches were scrutinized as separate case studies in which the different cases were formed according to different design teams: i) one researcher was in charge of the design and teachers were involved in the research process, ii) a research group was in charge of the design and students were involved in the research process, and iii) the design was done by student teams, the research was done collaboratively, and the design process was coordinated by a researcher. The research projects were conducted using mixed method approach, which enabled a comprehensive view on education design. In addition, the three central areas of design research: problem analysis, design solution and design process were included in the research, which was guided by the main research questions formed according to these central areas: 1) design solution: what kind of elements are included in ICT-based learning environments that support meaningful chemistry learning and diffusion of innovation, 2) problem analysis: what kind of new possibilities the designed learning environments offer for the support of meaningful chemistry learning, and 3) design process: what kind of opportunities and challenges does collaboration bring to the design of ICT-based learning environments? The main research questions were answered according to the analysis of the survey and observation data, six designed learning environments and ten design narratives from the three case studies. Altogether 139 chemistry teachers and teacher students were involved in the design processes. The data was mainly analysed by methods of qualitative content analysis. The first main result from the study give new information on the meaningful chemistry learning and the elements of ICT-based learning environment that support the diffusion of innovation, which can help in the development of future ICT-education design. When the designed learning environment was examined in the context of chemistry education, it was evident that an ICT-based chemistry learning environment supporting the meaningful learning of chemistry motivates the students and makes the teacher s work easier. In addition, it should enable the simultaneous fulfilment of several pedagogical goals and activate higher-level cognitive processes. The learning environment supporting the diffusion of ICT innovation is suitable for Finnish school environment, based on open source code, and easy to use with quality chemistry content. According to the second main result, new information was acquired about the possibilities of ICT-based learning environments in supporting meaningful chemistry learning. This will help in setting the goals for future ICT education. After the analysis of design solutions and their evaluations, it can be said that ICT enables the recognition of all elements that define learning environments (i.e. didactic, physical, technological and social elements). The research particularly demonstrates the significance of ICT in supporting students motivation and higher-level cognitive processes as well as versatile visualization resources for chemistry that ICT makes possible. In addition, research-based teaching method supports well the diffusion of studied innovation on individual level. The third main result brought out new information on the significance of collaboration in design research, which guides the design of ICT education development. According to the analysis of design narratives, it can be said that collaboration is important in the execution of scientifically reliable design research. It enables comprehensive requirement analysis and multifaceted development, which improves the reliability and validity of the research. At the same time, it sets reliability challenges by complicating documenting and coordination, for example. In addition, a new method for design research was developed. Its aim is to support the execution of complicated collaborative design projects. To increase the reliability and validity of the research, a model theory was used. It enables time-pound documenting and visualization of design decisions that clarify the process. This improves the reliability of the research. The validity of the research is improved by requirement definition through models. This way learning environments that meet the design goals can be constructed. The designed method can be used in education development from comprehensive to higher level. It can be used to recognize the needs of different interest groups and individuals with regard to processes, technology and substance knowledge as well as interfaces and relations between them. The developed method has also commercial potential. It is used to design learning environments for national and international market.

Individuals' Responsibility in Corporations

I discuss role responsibly, individual responsibility and collective responsibility in corporate multinational setting. My case study is about minerals used in electronics that come from the Democratic Republic of Congo. What I try to show throughout the thesis is how many things need to be taken into consideration when we discuss the responsibility of individuals in corporations. No easy and simple answers are available. Instead, we must keep in mind the complexity of the situation at all times, judging cases on individual basis, emphasizing the importance of individual judgement and virtue, as well as the responsibility we all share as members of groups and the wider society. I begin by discussing the demands that are placed on us as employees. There is always a potential for a conflict between our different roles and also the wider demands placed on us. Role demands are usually much more specific than the wider question of how we should act as human beings. The terminology of roles can also be misleading as it can create illusions about our work selves being somehow radically separated from our everyday, true selves. The nature of collective decision-making and its implications for responsibility is important too. When discussing the moral responsibility of an employee in a corporate setting, one must take into account arguments from individual and collective responsibility, as well as role ethics. Individual responsibility is not a separate or competing notion from that of collective responsibility. Rather, the two are interlinked. Individuals' responsibilities in collective settings combine both individual responsibility and collective responsibility (which is different from aggregate individual responsibility). In the majority of cases, both will apply in various degrees. Some members might have individual responsibility in addition to the collective responsibility, while others just the collective responsibility. There are also times when no-one bears individual moral responsibility but the members are still responsible for the collective part. My intuition is that collective moral responsibility is strongly linked to the way the collective setting affects individual judgements and moulds the decisions, and how the individuals use the collective setting to further their own ends. Individuals remain the moral agents but responsibility is collective if the actions in question are collective in character. I also explore the impacts of bureaucratic ethic and its influence on the individual. Bureaucracies can compartmentalize work to such a degree that individual human action is reduced to mere behaviour. Responsibility is diffused and the people working in the bureaucracy can come to view their actions to be outside the normal human realm where they would be responsible for what they do. Language games and rules, anonymity, internal power struggles, and the fragmentation of information are just some of the reasons responsibility and morality can get blurry in big institutional settings. Throughout the thesis I defend the following theses: ● People act differently depending on their roles. This is necessary for our society to function, but the more specific role demands should always be kept in check by the wider requirements of being a good human being. ● Acts in corporations (and other large collectives) are not reducible to individual actions, and cannot be explained fully by the behaviour of individual employees. ● Individuals are responsible for the actions that they undertake in the collective as role occupiers and are very rarely off the hook. Hiding behind role demands is usually only an excuse and shows a lack of virtue. ● Individuals in roles can be responsible even when the collective is not. This depends on if the act they performed was corporate in nature or not. ● Bureaucratic structure affects individual thinking and is not always a healthy environment to work in. ● Individual members can share responsibility with the collective and our share of the collective responsibility is strongly linked to our relations. ● Corporations and other collectives can be responsible for harm even when no individual is at fault. The structure and the policies of the collective are crucial. ● Socialization plays an important role in our morality at both work and outside it. We are all responsible for the kind of moral context we create. ● When accepting a role or a position in a collective, we are attaching ourselves with the values of that collective. ● Ethical theories should put more emphasis on good judgement and decision-making instead of vague generalisations. My conclusion is that the individual person is always in the centre when it comes to responsibility, and not so easily off the hook as we sometimes think. What we do, and especially who we choose to associate ourselves with, does matter and we should be more careful when we choose who we work for. Individuals within corporations are responsible for choosing that the corporation they associate with is one that they can ascribe to morally, if not fully, then at least for the most part. Individuals are also inclusively responsible to a varying degree for the collective activities they contribute to, even in overdetermined contexts. We all are responsible for the kind of corporations we choose to support through our actions as consumers, investors and citizens.

Phylogeography and demographic history of Lacerta lepida in the Iberian Peninsula

The Iberian Peninsula is recognized as an important refugial area for species survival and diversification during the climatic cycles of the Quaternary. Recent phylogeographic studies have revealed Iberia as a complex of multiple refugia. However, most of these studies have focused either on species with narrow distributions within the region or species groups that, although widely distributed, generally have a genetic structure that relates to pre-Quaternary cladogenetic events. In this study we undertake a detailed phylogeographic analysis of the lizard species, Lacerta lepida, whose distribution encompasses the entire Iberian Peninsula. We attempt to identify refugial areas, recolonization routes, zones of secondary contact and date demographic events within this species. Results support the existence of 6 evolutionary lineages (phylogroups) with a strong association between genetic variation and geography, suggesting a history of allopatric divergence in different refugia. Diversification within phylogroups is concordant with the onset of the Pleistocene climatic oscillations. The southern regions of several phylogroups show a high incidence of ancestral alleles in contrast with high incidence of recently derived alleles in northern regions. All phylogroups show signs of recent demographic and spatial expansions. We have further identified several zones of secondary contact, with divergent mitochondrial haplotypes occurring in narrow zones of sympatry. The concordant patterns of spatial and demographic expansions detected within phylogroups, together with the high incidence of ancestral haplotypes in southern regions of several phylogroups, suggests a pattern of contraction of populations into southern refugia during adverse climatic conditions from which subsequent northern expansions occurred. This study supports the emergent pattern of multiple refugia within Iberia but adds to it by identifying a pattern of refugia coincident with the southern distribution limits of individual evolutionary lineages. These areas are important in terms of long-term species persistence and therefore important areas for conservation.

Sanomattakin selvää? : "Ja", "mutta" ja "että" puheenvuoron lopussa

This study describes the use of utterances ending in the conjunctions "ja" (‘and’), "mutta" (‘but’) or "että" (‘that’/‘so’) in Finnish conversation. It argues that in spoken interaction, these conjunctions are not only used as linking elements but also as final elements in interactional and linguistic units. In contrast to more traditional views, the study shows that final conjunctions do not always indicate incompleteness or project continuation, but that they can also form recognizable points for turn-transition. In these contexts they can be reanalyzed as final particles that leave some aspect of the turn implicit. The data for the study consist of audio-taped telephone conversations and videotaped service encounters. Situated within the framework of conversation analysis and interactional linguistics, the study discusses the interactional uses of conjunction-final turns and their recognizability as possibly complete units in talk-in-interaction. The analysis of conjunction-final utterances focuses on 1) participant orientation, and 2) their recurrent contexts of use. The results show that the recipients of conjunction-final utterances often treat them as sufficient and complete in their contexts by displaying understanding or agreement. When the same speaker continues after a pause, it is not always clear that the continuation was "planned" in advance; it can also be reactive to lack of expected uptake. In these cases, a turn can be analyzed as potentially complete even if the same speaker decides to continue after a pause. In the light of these observations, the study confirms the incremental nature of spoken language. All the final conjunctions under examination have recurrent and recognizable contexts of use. Most typically, a conjunction-final utterance is produced in the service of some earlier claim by the same speaker. The conjunction-final utterance may 1) specify the earlier claim with a detailing list ("ja"), 2) legitimize it by presenting grounds ("että") or 3) partly back down from it by making a concession ("mutta"). Together with the earlier claim, conjunction-final utterances form recognizable discourse patterns that are used for argumentative purposes. In these contexts, conjunctions are used to relinquish the floor instead of functioning as turn-holding devices. In conclusion, the study discusses the emergence of conjunctions as final particles – how their development can be explained. Conjunction-type final particles emerge from recurring situations in which the future course of the conjunction-final turn-so-far is clear enough to remain unsaid, to be left to inference. More specifically, this ability to leave something to inference often lies in the fixed discourse patterns that are conventionalized and predictable and thus reducible.

Influence of an additional discrete elastic support on the stability of a Leipholz column

The stability characteristics of a conservatively loaded structure are expected to improve if additional supports are provided to the structure. The same, however, may not be said of a non-conservatively loaded structure; several factors, such as the location and stiffness of supports, type of structure and loading, have a significant influence on the stability characteristics. The influence of an arbitrarily located elastic support on the stability characteristics of a Leipholz column is examined.

Visuaalisen työmuistin vapaasti jaettavat resurssit : muistiedustusten lukumäärä ja tarkkuus ääriviivakuvioilla

According to the most prevalent view, there are 3-4 fixed "slots" in visual working memory for temporary storage. Recently this view has been challenged with a theory of dynamic resources which are restricted in their totality but can be freely allocated. The aim of this study is to clarify which one of the theories better describes the performance in visual working memory tasks with contour shapes. Thus in this study, the interest is in both the number of recalled stimuli and the precision of the memory representations. Stimuli in the experiments were radial frequency patterns, which were constructed by sinusoidally modulating the radius of a circle. Five observers participated in the experiment and it consisted of two different tasks. In the delayed discrimination task the number of recalled stimuli was measured with 2-interval forced choice task. Observer was shown serially two displays with 1, 5 s ISI (inter stimulus interval). Displays contained 1-6 patterns and they differed from each other with changed amplitude in one pattern. The participant s task was to report whether the changed pattern had higher amplitude in the first or in the second interval. The amount of amplitude change was defined with QUEST-procedure and the 75 % discrimination threshold was measured in the task. In the recall task the precision of the memory representations was measured with subjective adjustment method. First, observer was shown 1-6 patterns and after 1, 5 s ISI one location of the previously shown pattern was cued. Observer s task was to adjust amplitude of a probe pattern to match the amplitude of the pattern in working memory. In the delayed discrimination task the performance of all observes declined smoothly when the number of presented patterns was increased. The result supports the resource theory of working memory as there was no sudden fall in the performance. The amplitude threshold for one item was 0.01 0.05 and as the number of items increased from 1 to 6 there was a 4 15 -fold linear increase in the amplitude threshold (0.14 0.29). In the recall adjustment task the precision of four observers performance declined smoothly as the number of presented patterns was increased. The result also supports the resource theory. The standard deviation for one item was 0.03 0.05 and as the number of items increased from 1 to 6 there was a 2 3 -fold linear increase in the amplitude threshold (0.06 0.11). These findings show that the performance in a visual working memory task is described better according to the theory of freely allocated resources and not to the traditional slot-model. In addition, the allocation of the resources depends on the properties of the individual observer and the visual working memory task.

Euclideanization, topological theories, higher dimensions and all that

It is shown that the euclideanized Yukawa theory, with the Dirac fermion belonging to an irreducible representation of the Lorentz group, is not bounded from below. A one parameter family of supersymmetric actions is presented which continuously interpolates between the N = 2 SSYM and the N = 2 supersymmetric topological theory. In order to obtain a theory which is bounded from below and satisfies Osterwalder-Schrader positivity, the Dirac fermion should belong to a reducible representation of the Lorentz group and the scalar fields have to be reinterpreted as the extra components of a higher dimensional vector field.

Indian Ocean Dipole: Processes and impacts

Equatorial Indian Ocean is warmer in the east, has a deeper thermocline and mixed layer, and supports a more convective atmosphere than in the west. During certain years, the eastern Indian Ocean becomes unusually cold, anomalous winds blow from east to west along the equator and southeastward off the coast of Sumatra, thermocline and mixed layer lift up and the atmospheric convection gets suppressed. At the same time, western Indian Ocean becomes warmer and enhances atmospheric convection. This coupled ocean-atmospheric phenomenon in which convection, winds, sea surface temperature (SST) and thermocline take part actively is known as the Indian Ocean Dipole (IOD). Propagation of baroclinic Kelvin and Rossby waves excited by anomalous winds, play an important role in the development of SST anomalies associated with the IOD. Since mean thermocline in the Indian Ocean is deep compared to the Pacific, it was believed for a long time that the Indian Ocean is passive and merely responds to the atmospheric forcing. Discovery of the IOD and studies that followed demonstrate that the Indian Ocean can sustain its own intrinsic coupled ocean-atmosphere processes. About 50% percent of the IOD events in the past 100 years have co-occurred with El Nino Southern Oscillation (ENSO) and the other half independently. Coupled models have been able to reproduce IOD events and process experiments by such models – switching ENSO on and off – support the hypothesis based on observations that IOD events develop either in the presence or absence of ENSO. There is a general consensus among different coupled models as well as analysis of data that IOD events co-occurring during the ENSO are forced by a zonal shift in the descending branch of Walker cell over to the eastern Indian Ocean. Processes that initiate the IOD in the absence of ENSO are not clear, although several studies suggest that anomalies of Hadley circulation are the most probable forcing function. Impact of the IOD is felt in the vicinity of Indian Ocean as well as in remote regions. During IOD events, biological productivity of the eastern Indian Ocean increases and this in turn leads to death of corals over a large area.Moreover, the IOD affects rainfall over the maritime continent, Indian subcontinent, Australia and eastern Africa. The maritime continent and Australia suffer from deficit rainfall whereas India and east Africa receive excess. Despite the successful hindcast of the 2006 IOD by a coupled model, forecasting IOD events and their implications to rainfall variability remains a major challenge as understanding reasons behind an increase in frequency of IOD events in recent decades.

Noble metal ionic sites for catalytic hydrogen combustion: spectroscopic insights

A catalytic hydrogen combustion reaction was carried out over noble metal catalysts substituted in ZrO2 and TiO2 in ionic form. The catalysts were synthesized by the solution combustion technique. The compounds showed high activity and CO tolerance for the reaction. The activity of Pd and Pt ion substituted TiO2 was comparable and was higher than Pd and Pt ion substituted ZrO2. The mechanisms of the reaction over the two supports were proposed by making use of the X-ray photoelectron spectroscopy and FT infrared spectroscopic observations. The reaction over ZrO2 supported catalysts was proposed to take place by the utilization of the surface hydroxyl groups while the reaction over TiO2 supported catalysts was hypothesized to be a hybrid mechanism utilizing surface hydroxyl groups and the lattice oxygen.

Literature Review: Investigating Drug Transport at the Blood-Brain Barrier and the Effects of P-glycoprotein on the Brain Distribution of Drugs.

The blood-brain barrier (BBB) is a unique barrier that strictly regulates the entry of endogenous substrates and xenobiotics into the brain. This is due to its tight junctions and the array of transporters and metabolic enzymes that are expressed. The determination of brain concentrations in vivo is difficult, laborious and expensive which means that there is interest in developing predictive tools of brain distribution. Predicting brain concentrations is important even in early drug development to ensure efficacy of central nervous system (CNS) targeted drugs and safety of non-CNS drugs. The literature review covers the most common current in vitro, in vivo and in silico methods of studying transport into the brain, concentrating on transporter effects. The consequences of efflux mediated by p-glycoprotein, the most widely characterized transporter expressed at the BBB, is also discussed. The aim of the experimental study was to build a pharmacokinetic (PK) model to describe p-glycoprotein substrate drug concentrations in the brain using commonly measured in vivo parameters of brain distribution. The possibility of replacing in vivo parameter values with their in vitro counterparts was also studied. All data for the study was taken from the literature. A simple 2-compartment PK model was built using the Stella™ software. Brain concentrations of morphine, loperamide and quinidine were simulated and compared with published studies. Correlation of in vitro measured efflux ratio (ER) from different studies was evaluated in addition to studying correlation between in vitro and in vivo measured ER. A Stella™ model was also constructed to simulate an in vitro transcellular monolayer experiment, to study the sensitivity of measured ER to changes in passive permeability and Michaelis-Menten kinetic parameter values. Interspecies differences in rats and mice were investigated with regards to brain permeability and drug binding in brain tissue. Although the PK brain model was able to capture the concentration-time profiles for all 3 compounds in both brain and plasma and performed fairly well for morphine, for quinidine it underestimated and for loperamide it overestimated brain concentrations. Because the ratio of concentrations in brain and blood is dependent on the ER, it is suggested that the variable values cited for this parameter and its inaccuracy could be one explanation for the failure of predictions. Validation of the model with more compounds is needed to draw further conclusions. In vitro ER showed variable correlation between studies, indicating variability due to experimental factors such as test concentration, but overall differences were small. Good correlation between in vitro and in vivo ER at low concentrations supports the possibility of using of in vitro ER in the PK model. The in vitro simulation illustrated that in the simulation setting, efflux is significant only with low passive permeability, which highlights the fact that the cell model used to measure ER must have low enough paracellular permeability to correctly mimic the in vivo situation.

Jos olisin viisas niin siivoisin : Lasten luovat prosessit päiväkodissa

It has been found usually to talk in the early childhood education in connection with the creativity about arts and skills and about play. In this treatise, the creativity is approached besides play but also from the point of view of the creativity of the everyday. The starting point for the study is the view according to which the creativity is complex interaction between a creative person and an environment. The theoretical body of the study is the Componential theory of creativity of Amabile (1996). The process which is open and product which is new and suitable or acceptable were defined creative. In the opinion of many researchers, the creativity is a phenomenon that has determined in a certain time and place so the creativity is examined from the point of view of the social constructionism. As creative processes in the day nursery it has been defined pretend play, child´s involvement and children´s agentive perception which is based on the Children´s agentive perception theory of Reunamo (2007). The purpose of the study is to clarify how the child's personal factors and the social environment affect the creative processes of children in the day nursery. This Master's thesis is based on the Children' s agentive perception uncovered study led by Jyrki Reunamo (2010) which was carried out in the spring of 2010 in Keski-Uusimaa and in Hämeenlinna and Taiwan. From the study, a name has also been used "on the sources of Orientation", a research project and development project. The study includes the children's evaluation sector, the observation sector, the children's interview sector and the evaluation sector of the pedagogic environment. 891 Children 1-7 year-old by age participated in the study. All the sectors which belong to the study of Reunamo were utilized in this treatise and the Finnish day nurseries or preschool groups which had participated in the study were marked off as the target group. The main component analysis, sum variables, the correlation coefficients, Mann-Whitney s U-test and Kruskall-Wallas test were used for the statistical examination of the quantitative material. In this treatise it was noticed, both the personal properties of the child and a social environment, that they affected all the examined creative processes which also had a significant connection with each other statistically. The definition of creativity was filled best by the participative answers. However, the number of the participative answers was only 8% in the questions concerning adults. That raised the question whether an attempt should be made to have effect so that the children's better participation also in the interaction with the adults would be possible in the educational culture of the day nursery. In the further study, the conscious building of the social environment which supports the creativity from a social constructionism point of view could indeed be an interesting task. The treatise is suitable for an examination of the interaction between the child's person and a social environment especially from the point of view of the creativity.