Effects of neurotrophins on synaptic protein expression in the visual cortex of dark reared rats.

Total lack of visual experience [dark rearing (DR)] is known to prolong the critical period and delay development of sensory functions in mammalian visual cortex. Recent results show that neurotrophins (NTs) counteract the effects of DR on functional properties of visual cortical cells and exert a strong control on critical period duration. NTs are known to modulate the development and synaptic efficacy of neurotransmitter systems that are affected by DR. However, it is still unknown whether the actions of NTs in dark-reared animals involve interaction with neurotransmitter systems. We have studied the effects of DR on the expression of key molecules in the glutamatergic and GABAergic systems in control and NT-treated animals. We have found that DR reduced the expression of the NMDA receptor 2A subunit and its associated protein PSD-95 (postsynaptic density-95), of GRIP (AMPA glutamate receptor interacting protein), and of the biosynthetic enzyme GAD (glutamic acid decarboxylase). Returning dark-reared animals to light for 2 hr restored normal expression of the above-mentioned proteins almost completely. NT treatment specifically counteracts DR effects; NGF acts primarily on the NMDA system, whereas BDNF acts primarily on the GABAergic system. Finally, the action of NT4 seems to involve both excitatory and inhibitory systems. These data demonstrate that different NTs counteract DR effects by modulating the expression of key molecules of the excitatory and inhibitory neurotransmitter systems

Nursing Ethics Education in Finland from the Perspective of Codes of Ethics

The purpose of this study was to analyze nursing ethics education from the perspective of nurses’ codes of ethics in the basic nursing education programmes in polytechnics in Finland with the following research questions: What is known about nurses’ codes in practice and education, what contents of the codes are taught, what teaching and evaluation methods are used, which demographic variables are associated with the teaching, what is nurse educators’ adequacy of knowledge to teach the codes and nursing students’ knowledge of and ability to apply the codes, and what are participants’ opinions of the need and applicability of the codes, and their importance in nursing ethics education. The aim of the study was to identify strengths and possible problem areas in teaching of the codes and nursing ethics in general. The knowledge gained from this study can be used for developing nursing ethics curricula and teaching of ethics in theory and practice. The data collection was targeted to all polytechnics in Finland providing basic nursing education (i.e. Bachelor of Health Care). The target groups were all nurse educators teaching ethics and all graduating nursing students in the academic year of 2006. A total of 183 educators and 214 students from 24 polytechnics participated. The data was collected using a structured questionnaire with four open-ended questions, designed for this study. The data was analysed by SPSS (14.0) and the open-ended questions by inductive content analysis. Descriptive statistics were used to summarize the data. Inferential statistics were used to estimate the differences between the participant groups. The reliability of the questionnaire was estimated with Cronbach’s coefficient alpha. The literature review revealed that empirical research on the codes was scarce, and minimal in the area of education. Teaching of nurses’ codes themselves and the embedded ethical concepts was extensive, teaching of the functions of the codes and related laws and agreements was moderate, but teaching of the codes of other health care professions was modest. Issues related to the nurse-patient relationship were emphasised. Wider social dimensions of the codes were less emphasized. Educators’ and students’ descriptions of teaching emphasized mainly the same teaching contents, but there were statistically significant differences between the groups in that educators assessed their teaching to be more extensive than what students had perceived it had been. T he use of teaching and evaluation methods was rather narrow and conventional. However, educators’ and students’ descriptions of the used methods differed statistically significantly. Students’ knowledge of the codes and their ability to apply them in practice was assessed as mediocre by educators and by students themselves. Most educators assessed their own knowledge of the codes as adequate to teach the codes, as did most of the students. Educators who regarded their knowledge as adequate taught the codes more extensively than those who assessed their knowledge as less adequate. Also students who assessed their educators’ knowledge as adequate perceived the teaching of the codes to be more extensive. Otherwise educators’ and students’ demographic variables had little association with their descriptions of the teaching. According to the participants, nurses need their own codes, and they are also regarded as applicable in practice. The codes are an important element in nursing ethics education, but their teaching needs development. Further research should focus on the organization of ethics teaching in the curricula, the teaching process, and on the evaluation of the effectiveness of ethics education and on educators’ competence. Also the meaning and functions of the codes at all levels of nursing deserve attention. More versatile use of research methods would be beneficial in gaining new knowledge.

Studies on the Multifaceted Interaction of Atoms and an Electromagnetic Field

In this Thesis the interaction of an electromagnetic field and matter is studied from various aspects in the general framework of cold atoms. Our subjects cover a wide spectrum of phenomena ranging from semiclassical few-level models to fully quantum mechanical interaction with structured reservoirs leading to non-Markovian open quantum system dynamics. Within closed quantum systems, we propose a selective method to manipulate the motional state of atoms in a time-dependent double-well potential and interpret the method in terms of adiabatic processes. Also, we derive a simple wave-packet model, based on distributions of generalized eigenstates, explaining the finite visibility of interference in overlapping continuous-wave atom lasers. In the context of open quantum systems, we develop an unraveling of non-Markovian dynamics in terms of piecewise deterministic quantum jump processes confined in the Hilbert space of the reduced system - the non-Markovian quantum jump method. As examples, we apply it for simple 2- and 3-level systems interacting with a structured reservoir. Also, in the context of ion-cavity QED we study the entanglement generation based on collective Dicke modes in experimentally realistic conditions including photonic losses and an atomic spontaneous decay.

The role of selection in functional explanations

In this essay I will argue that natural selection is more important to functional explanations than what has been thought in some of the literature in philosophy of biology. I start by giving a brief overview of the two paradigms cases of functional explanations: etiological functions and causal-role functions. i then consider one particular attempt to conciliate both perspectives given by David Buller (1998). Buller's trial to conciliate both etiological functions and causal-role functions results in what he calls a weak etiological theory. I argue that Buller has not succeeded in his construal of the weak etiological theory: he underestimates the role that selective processes have in functional explanations and so his theory may not be classified as an etiologial theory. As an alternative, I consider the account of etiological functions given by Ruth Millikan (1984) and I argue that Millikan's theory is more comprehensive to assess contentious case in biology like exaptations. Finally, I conclude by analyzing where the adoption of Millikan's theory leave us. I argue, contrary to Millikan and others, that once we assume the importance of natural selection in functional explanations, there is no strong reason to resist a linguistic reform of the word function and hence that the attempts to conciliate both etiological functions and causal-role functions are misplaced.

Cognitive Functions After Traumatic Brain Injury. A 30-year Follow-up Study

Many cognitive deficits after TBI (traumatic brain injury) are well known, such as memory and concentration problems, as well as reduced information-processing speed. What happens to patients and cognitive functioning after immediate recovery is poorly known. Cognitive functioning is flexible and may be influenced by genetic, psychological and environmental factors decades after TBI. The general aim of this thesis was to describe the long-term cognitive course after TBI, to find variables that may contribute to it, and how the cognitive functions after TBI are associated with specific medical factors and reduced survival. The original study group consisted of 192 patients with TBI who were originally assessed with the Mild Deterioration Battery (MDB) on average two years after the injury, during the years 1966 – 1972. During a 30-year follow-up, we studied the risks for reduced survival, and the mortality of the patients was compared with the general population using the Standardized Mortality Ratio (SMR). Sixty-one patients were re-assessed during 1998-2000. These patients were evaluated with the MDB, computerized testing, and with various other neuropsychological methods for attention and executive functions. Apolipoprotein-E (ApoE) genotyping and magnetic resonance imaging (MRI) based on volumetric analysis of the hippocampus and lateral ventricles were performed. Depressive symptoms were evaluated with the short form of the Beck depression inventory. The cognitive performance at follow-up was compared with a control group that was similar to the study group in regard to age and education. The cognitive outcome of the patients with TBI varied after three decades. The majority of the patients showed a decline in their cognitive level, the rest either improved or stayed at the same level. Male gender and higher age at injury were significant risk factors for the decline. Whereas most cognitive domains declined during the follow-up, semantic memory behaved in the opposite way, showing recovery after TBI. In the follow-up assessment, the memory decline and impairments in the set-shifting domain of executive functions were associated with MRI-volumetric measures, whereas reduction in information-processing speed was not associated with the MRI measures. The presence of local contusions was only weakly associated with cognitive functions. Only few cognitive methods for attention were capable of discriminating TBI patients with and without depressive symptoms. On the other hand, most complex attentional tests were sensitive enough to discriminate TBI patients (non-depressive) from controls. This means that complex attention functions, mediated by the frontal lobes, are relatively independent of depressive symptoms post-TBI. The presence of ApoE4 was associated with different kinds of memory processes including verbal and visual episodic memory, semantic memory and verbal working memory, depending on the length of time since TBI. Many other cognitive processes were not affected by the presence of ApoE4. Age at injury and poor vocational outcome were independent risk factors for reduced survival in the multivariate analysis. Late mortality was higher among younger subjects (age < 40 years at death) compared with the general population which should be borne in mind when assessing the need for rehabilitation services and long-term follow-up after TBI.

Boron influence on concentration of polyols and other sugars in Eucalyptus

Although the functions of the element Boron (B) in plants have not been sufficiently clarified, several hypotheses have been raised. Some of the functions attributed to this element are synthesis and transport of carbohydrates. To evaluate the effect of B on the synthesis of some polyols and sugars in Eucalyptus grandis and hybrids "urograndis", these species were submitted to situations of supply and restriction of B. The experiment was carried out in a greenhouse, arranged in a randomized block design in a 2 x 2 factorial scheme, with 5 replicates of each genotype. The B levels were provided in the form of nutrient solution. No significant difference was observed in the content of mannitol, sorbitol, myo-inositol and scyllo-inositol and sugars α-glucose and β-glucose between E. grandis and hybrids. Arabinose was the only one to present a higher content in E. grandis on restriction of B. The effect of the presence of B was very expressive, but regarding B supply, the plants showed significant increase in the synthesis of the compounds evaluated.

Creating possibilities for collective creativity : Brokerage Functions in Practice-Based Innovation

In the network era, creative achievements like innovations are more and more often created in interaction among different actors. The complexity of today‘s problems transcends the individual human mind, requiring not only individual but also collective creativity. In collective creativity, it is impossible to trace the source of new ideas to an individual. Instead, creative activity emerges from the collaboration and contribution of many individuals, thereby blurring the contribution of specific individuals in creating ideas. Collective creativity is often associated with diversity of knowledge, skills, experiences and perspectives. Collaboration between diverse actors thus triggers creativity and gives possibilities for collective creativity. This dissertation investigates collective creativity in the context of practice-based innovation. Practice-based innovation processes are triggered by problem setting in a practical context and conducted in non-linear processes utilising scientific and practical knowledge production and creation in cross-disciplinary innovation networks. In these networks diversity or distances between innovation actors are essential. Innovation potential may be found in exploiting different kinds of distances. This dissertation presents different kinds of distances, such as cognitive, functional and organisational which could be considered as sources of creativity and thus innovation. However, formation and functioning of these kinds of innovation networks can be problematic. Distances between innovating actors may be so great that a special interpretation function is needed – that is, brokerage. This dissertation defines factors that enhance collective creativity in practice-based innovation and especially in the fuzzy front end phase of innovation processes. The first objective of this dissertation is to study individual and collective creativity at the employee level and identify those factors that support individual and collective creativity in the organisation. The second objective is to study how organisations use external knowledge to support collective creativity in their innovation processes in open multi-actor innovation. The third objective is to define how brokerage functions create possibilities for collective creativity especially in the context of practice-based innovation. The research objectives have been studied through five substudies using a case-study strategy. Each substudy highlights various aspects of creativity and collective creativity. The empirical data consist of materials from innovation projects arranged in the Lahti region, Finland, or materials from the development of innovation methods in the Lahti region. The Lahti region has been chosen as the research context because the innovation policy of the region emphasises especially the promotion of practice-based innovations. The results of this dissertation indicate that all possibilities of collective creativity are not utilised in internal operations of organisations. The dissertation introduces several factors that could support collective creativity in organisations. However, creativity as a social construct is understood and experienced differently in different organisations, and these differences should be taken into account when supporting creativity in organisations. The increasing complexity of most potential innovations requires collaborative creative efforts that often exceed the boundaries of the organisation and call for the involvement of external expertise. In practice-based innovation different distances are considered as sources of creativity. This dissertation gives practical implications on how it is possible to exploit different kinds of distances knowingly. It underlines especially the importance of brokerage functions in open, practice-based innovation in order to create possibilities for collective creativity. As a contribution of this dissertation, a model of brokerage functions in practice-based innovation is formulated. According to the model, the results and success of brokerage functions are based on the context of brokerage as well as the roles, tasks, skills and capabilities of brokers. The brokerage functions in practice-based innovation are also possible to divide into social and cognitive brokerage.

The Dual Role of HIF Hydroxylase PHD3 in Cancer Cell Survival

Most advanced tumours face periods of reduced oxygen availability i.e. hypoxia. During these periods tumour cells undergo adaptive changes enabling their survival under adverse conditions. In cancer hypoxia-induced cellular changes cause tumour progression, hinder cancer treatment and are indicative of poor prognosis. Within cells the main regulator of hypoxic responses is the hypoxia-inducible factor (HIF). HIF governs the expression of over a hundred hypoxia-inducible genes that regulate a number of cellular functions such as angiogenesis, glucose metabolism and cell migration. Therefore the activity of HIF must be tightly governed. HIF is regulated by a family of prolyl hydroxylase enzymes, PHDs, which mark HIF for destruction in normoxia. Under hypoxic conditions PHDs lose much of their enzymatic activity as they need molecular oxygen as a cofactor. Out of the three PHDs (PHD1, 2 and 3) PHD2 has been considered to be the main HIF-1 regulator in normoxic conditions. PHD3 on the other hand shows the most robust induction in response to oxygen deprivation and it has been implied as the main HIF-1 regulator under prolonged hypoxia. SQSTM1/p62 (p62) is an adaptor protein that functions through its binding motifs to bring together proteins in order to regulate signal transduction. In non-stressed situations p62 levels are kept low but its expression has been reported to be upregulated in many cancers. It has a definitive role as an autophagy receptor and as such it serves a key function in cancer cell survival decisions. In my thesis work I evaluated the significance of PHD3 in cancer cell and tumour biology. My results revealed that PHD3 has a dual role in cancer cell fate. First, I demonstrated that PHD3 forms subcellular protein aggregates in oxygenated carcinoma cells and that this aggregation promotes apoptosis induction in a subset of cancer cells. In these aggregates an adaptor protein SQSTM1/p62 interacts with PHD3 and in so doing regulates PHD3 expression. SQSTM1/p62 expression is needed to keep PHD3 levels low in normoxic conditions. Its levels rapidly decrease in response to hypoxia allowing PHD3 protein levels to be upregulated and the protein to be diffusely expressed throughout the cell. The interaction between PHD3 and SQSTM1/p62 limits the ability of PHD3 to function on its hydroxylation target protein HIF-1alpha. Second, the results indicate that when PHD3 is upregulated under hypoxia it protects cancer cells by allowing cell cycle to proceed from G1 to S-phase. My data demonstrates that PHD3 may either cause cell death or protect the cells depending on its expression pattern and the oxygen availability of tumours.

Lagrangian multipliers for coast-arcs of optimum space trajectories

Some properties of generalized canonical systems - special dynamical systems described by a Hamiltonian function linear in the adjoint variables - are applied in determining the solution of the two-dimensional coast-arc problem in an inverse-square gravity field. A complete closed-form solution for Lagrangian multipliers - adjoint variables - is obtained by means of such properties for elliptic, circular, parabolic and hyperbolic motions. Classic orbital elements are taken as constants of integration of this solution in the case of elliptic, parabolic and hyperbolic motions. For circular motion, a set of nonsingular orbital elements is introduced as constants of integration in order to eliminate the singularity of the solution.

Tuning cell motility : roles of nestin and vimentin in cancer cell invasion and motility

The cytoskeleton is a key feature of both prokaryotic and eukaryotic cells. Itis comprised of three protein families, one of which is the intermediate filaments (IFs). Of these, the IFs are the largest and most diverse. The IFs are expressed throughout life, and are involved in the regulation of cell differentiation, homeostasis, ageing and pathogenesis. The IFs not only provide structural integrity to the cell, they are also involved in a range of cellular functions from organelle trafficking and cell migration to signalling transduction. The IFs are highly dynamic proteins, able to respond and adapt their network rapidly in response to intra- and extra- cellular cues. Consequently they interact with a whole host of cellular signalling proteins, regulating function, and activity, and cellular localisation. While the function of some of the better-known IFs such as the keratins is well studied, the understanding of the function of two IFs, nestin and vimentin, is poor. Nestin is well known as a marker of differentiation and is expressed in some cancers. In cancer, nestin is primarily described as is a promoter of cell motility, however, how it fulfils this role remains undefined. Vimentin too is expressed in cancer, and is known to promote cell motility and is used as a marker for epithelial to mesenchymal transition (EMT). It is only in the last decade that studies have addressed the role that vimentin plays in cell motility and EMT. This work provides novel insight into how the IFs, nestin and vimentin regulate cell motility and invasion. In particular we show that nestin regulates the cellular localisation and organisation of two key facilitators of cell migration, focal adhesion kinase and integrins. We identify nestin as a regulator of extracellular matrix degradation and integrin-mediated cell invasion. Two further studies address the specific regulation of vimentin by phosphorylation. A detailed characterisation study identified key phosphorylation sites on vimentin, which are critical for proper organisation of the vimentin network. Furthermore, we show that the bioactive sphingolipids are vimentin network regulators. Specifically, the sphingolipids induced RhoA kinasedependent (ROCK) phosphorylation at vimentin S71, which lead to filament reorganisation and inhibition of cell migration. Together these studies shed new light into the regulation of nestin and vimentin during cell motility.

Forecasting of wind speeds and directions with artificial neural networks

In this master’s thesis, wind speeds and directions were modeled with the aim of developing suitable models for hourly, daily, weekly and monthly forecasting. Artificial Neural Networks implemented in MATLAB software were used to perform the forecasts. Three main types of artificial neural network were built, namely: Feed forward neural networks, Jordan Elman neural networks and Cascade forward neural networks. Four sub models of each of these neural networks were also built, corresponding to the four forecast horizons, for both wind speeds and directions. A single neural network topology was used for each of the forecast horizons, regardless of the model type. All the models were then trained with real data of wind speeds and directions collected over a period of two years in the municipal region of Puumala in Finland. Only 70% of the data was used for training, validation and testing of the models, while the second last 15% of the data was presented to the trained models for verification. The model outputs were then compared to the last 15% of the original data, by measuring the mean square errors and sum square errors between them. Based on the results, the feed forward networks returned the lowest generalization errors for hourly, weekly and monthly forecasts of wind speeds; Jordan Elman networks returned the lowest errors when used for forecasting of daily wind speeds. Cascade forward networks gave the lowest errors when used for forecasting daily, weekly and monthly wind directions; Jordan Elman networks returned the lowest errors when used for hourly forecasting. The errors were relatively low during training of the models, but shot up upon simulation with new inputs. In addition, a combination of hyperbolic tangent transfer functions for both hidden and output layers returned better results compared to other combinations of transfer functions. In general, wind speeds were more predictable as compared to wind directions, opening up opportunities for further research into building better models for wind direction forecasting.

The brain decade in debate: VII. Neurobiology of sleep and dreams

This article is a transcription of an electronic symposium held on February 5, 2001 by the Brazilian Society of Neuroscience and Behavior (SBNeC) during which eight specialists involved in clinical and experimental research on sleep and dreaming exposed their personal experience and theoretical points of view concerning these highly polemic subjects. Unlike most other bodily functions, sleep and dreaming cannot, so far, be defined in terms of definitive functions that play an ascribable role in maintaining the organism as a whole. Such difficulties appear quite clearly all along the discussions. In this symposium, concepts on sleep function range from a protective behavior to an essential function for maturation of the nervous system. Kleitman's hypothesis [Journal of Nervous and Mental Disease (1974), 159: 293-294] was discussed, according to which the basal state is not the wakeful state but sleep, from which we awake to eat, to protect ourselves, to procreate, etc. Dreams, on the other hand, were widely discussed, being considered either as an important step in consolidation of learning or simply the conscious identification of functional patterns derived from the configuration of released or revoked memorized information.

Cissampelos sympodialis Eichl (Menispermaceae) leaf extract induces interleukin-10-dependent inhibition of Trypanosoma cruzi killing by macrophages

The aqueous fraction of the ethanolic extract (AFL) of Cissampelos sympodialis Eichl (Menispermaceae), popularly known as milona, has been shown to have both immunosuppressive and anti-inflammatory effects. In the present study we investigated the modulation of macrophage antimicrobicidal activity by in vitro treatment with the extract from C. sympodialis. Normal and thioglycolate-elicited mouse peritoneal macrophages were infected in vitro with the protozoan Trypanosoma cruzi DM28c clone. We observed that the AFL (used at doses ranging from 13 to 100 µg/ml) increased T. cruzi growth and induced a 75% reduction in nitric oxide production. This inhibition could be mediated by the stimulation of macrophage interleukin-10 (IL-10) secretion since the in vitro treatment with the AFL stimulated IL-10 production by T. cruzi-infected macrophages. These results suggest that the anti-inflammatory effect of the AFL from C. sympodialis could be, at least in part, mediated by the inhibition of macrophage functions and that the inhibition of macrophage microbicidal activity induced by the C. sympodialis extract may be mediated by the decrease in macrophage function mediated by interleukin-10 production.

Distribution of biglycan and decorin in rat dental tissue

Biglycan and decorin are small leucine-rich proteoglycans that play several biological and structural roles in different tissues and organs. Several reports have indicated that biglycan participates in odontoblast and ameloblast differentiation and in the calcification process. In the present study we show that the expression of biglycan changes from within the ameloblasts and odontoblasts to the extracellular space according to the stage of animal development. In predentin and in the pulp space, however, biglycan was continually expressed throughout the period of investigation. In contrast, decorin was absent in odontoblasts and in ameloblasts and was exclusively expressed in predentin throughout the period of observation. In young rats, however, decorin was expressed in the extracellular spaces of the pulp, where it was concentrated mainly in the peripheral pulp.

Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60- to 90-day-old Wistar rats, N = 5-11) and audiogenic seizure (female 60- to 90-day-old Wistar audiogenic rats, N = 5-11) models of epilepsy. Naloxone (5 mg/kg, sc) significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test), suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc) was demonstrable. The acute (120 mg/kg, ip) and chronic (25 mg/kg, ip, twice a day/4 days) administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip) used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures.