997 resultados para 03271246 TM-17
Resumo:
Serum and synovial antibody reactivities of caprine arthritis encephalitis virus (CAEV) infected goats were assessed by Western blotting against purified CAEV antigen and the greatest intensity of reactivity in the serum of arthritic goats was to the gp45 transmembrane protein (TM). The extracytoplasmic domain of the TM gene was cloned into a pGEX vector and expressed in Escherichia coil as a glutathione S transferase fusion protein (GST-TM). This clone was found to be 90.5 and 89.2% homologous to published sequences of CAEV TM gene. Serum of 16 goats naturally infected with CAEV were examined by Western blotting for reactivity to the fusion protein. Antibody reactivity to the GST-TM correlated with clinically detectable arthritis (R = 0.642, P ≤ 0.007). The hypothesis that the immune response to the envelope proteins of the CAEV contributes to the severity of arthritis in goats naturally infected with CAEV via epitope mimicry was tested. Antibodies from 5 CAEV infected goats were affinity purified against the GST-TM fusion protein and tested for cross-reactivity with a series of goat synovial extracts and proteogylcans. No serum antibody response or cross-reactivity of affinity purified antibodies could be detected. Peptides of the CAEV SU that were predicted to be linear epitopes and a similar heat shock protein 83 (HSP) peptide identified by database searching, were synthesized and tested for reactivity in CAEV goats using ELISA, in vitro lymphocyte proliferation and delayed type hypersensitivity (DTH) assays. Peripheral blood lymphocytes from 10 of 17 goats with long term natural CAEV infections proliferated in vitro in response to CAEV and in vivo 3 of 7 CAEV infected goats had a DTH reaction to CAEV antigen. However, none of the peptides elicited significant cell mediated immune responses from CAEV infected goats. No antibody reactivity to the SU peptides or HSP peptide was found. We observed that the antibody reactivity to the CAEV TM protein associated with severity of arthritis however epitope mimicry by the envelope proteins of CAEV is unlikely to be involved.
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The proinflammatory cytokine IL-17 has an important role in pathogenesis of several inflammatory diseases. In immune-mediated joint diseases, IL-17 can induce secretion of other proinflammatory cytokines such as IL-1, IL-6 and TNF, as well as matrix metalloproteinase enzymes, leading to inflammation, cartilage breakdown, osteoclastogenesis and bone erosion. In animal models of inflammatory arthritis, mice deficient in IL-17 are less susceptible to development of disease. The list of IL-17-secreting cells is rapidly growing, and mast cells have been suggested to be a dominant source of IL-17 in inflammatory joint disease. However, many other innate sources of IL-17 have been described in both inflammatory and autoinflammatory conditions, raising questions as to the role of mast cells in orchestrating joint inflammation. This article will critically assess the contribution of mast cells and other cell types to IL-17 production in the inflammatory milieu associated with inflammatory arthritis, understanding of which could facilitate targeted therapeutic approaches. © 2013 Macmillan Publishers Limited. All rights reserved.
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The role of the CTLA-4 antigen in the development of autoimmune diseases is well documented, with several autoimmune disorders showing association or linkage with the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however, remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse models of RA and genetic studies in humans have given contrasting results. We have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA-4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite the high statistical power to detect even a weak susceptibility effect, no significant association was found. We also analysed the distribution of the allele and genotype frequencies with respect to the presence of the shared epitope (a known RA susceptibility factor) and found no statistically significant differences. We conclude that, although the importance of the B7-CTLA-4 interaction in the development of RA can not be excluded, the CTLA-4 gene is unlikely to be a predisposing factor to this disease.
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Addition of estradiol 17-beta to first trimester human placental minces resulted in an increased synthesis of a protein of apparent molecular weight 45 kDa. The specific involvement of estrogen in the stimulation of this protein was established by demonstrating a reduction in the level of this protein by the addition of CCS 16949 A, an inhibitor of aromatase, a key enzyme in the biosynthesis of estradiol 17-beta and ICI 182,780, an estrogen receptor antagonist. The protein was purified to homogeneity and N-terminal sequencing of two of the internal peptides obtained by enzymatic digestion of the protein, as well as the absence of a free N-terminal indicated that it could be actin. This was confirmed by Western blotting using commercially available actin antiserum. The role of estradiol 17-beta in the stimulation of actin synthesis in human placenta was also established by monitoring the quantitative inhibition of DNase I by actin.
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The structure and conformation of a second crystalline modification of 19-nortestosterone has been determined by X-ray methods. M r = 274, monoclinic P2 l, a=9.755(2), b= 11.467(3), c= 14.196(3)/L fl=101.07(2) ° , V=1558.4 (8) A 3, Z=4, Ox= I. 168 g cm -3, Mo Ka, 2 = 0.7107 ,/k, ~ = 0.80 cm -l, F(000) = 600, T= 300 K. R = 0.060 for 2158 observed reflections. The two molecules in the asymmetric unit show significant differences in the A-ring conformation from that of the previously reported form of the title compound [Precigoux, Busetta, Courseille & Hospital (1975). Acta Cryst. B31, 1527-1532]. The l a,2fl-half-chair conformation of the A ring increases its conformational freedom compared with testosterone.
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Coordination and juxtaposed sentences The object of this study is the examination of the relations between juxtaposed clauses in contemporary French. The matter in question is sentences which are composed of several clauses adjoined without a conjunction or other connector, as in: Je détournai les yeux, mon c ur se mit à battre. The aim of the study is to determine, which quality is the relation in these sentences and, on the other hand, what is the part of the coordination there. Furthermore, what is this relation of coordination, which, according to some grammars, manifests through a conjunction of coordination, but which, according to some others is marked in juxtaposed sentences through different features. The study is based on a corpus of written French from literary and journalistic text sources. Syntactic, semantic and textual properties in the clauses are discussed. The analysis points to differences so, it has been noted, in each case, if one of the clauses is affirmative and the other negative and if in the second clause, the subject has not been repeated. Also, an analysis has been made on the ground of the tense, mode, phrase structure type, and thematic structure, taking into account, in each case, if the clauses are identical or different. Punctuation has been one of the properties considered. The final aim has been to eliminate gradually, based on the partition of properties, subordinate sentences, so that only the hard core of coordinate sentences remains. In this way, the coordination could be defined similarly as the phoneme is defined as a group of distinctive features. The quantitative analyses have led to the conclusion that the sentences which, from a semantic point of view, are interpreted as coordinating, contain the least of these differences, while the sentences which can be considered as subordinating present the most of these differences. The conditions of coordination are, in that sense, hierarchical, so that the syntactic constraints have to make room for semantic, textual and cognitive factors. It is interesting to notice that everyone has the ability to produce correct coordinating structures and recognize incorrect coordinating structures. This can be explained by the human ability to categorize which has been widely researched in the semantic of prototype. The study suggests that coordination and subordination could be considered as prototypical cognitive categories based on different linguistic and pragmatic features.
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This thesis is a preliminary phonological description of the Tibetan-related Denjongka language of Sikkim, India. Because the language has not been much researched and the previous studies have focused on other issues than phonology, the present paper is the first of its kind. The data for this thesis was gathered in Gangtok, the capital of Sikkim, from March to May 2004. I had four language informants from four different locations in Sikkim who spoke different dialects of Denjongka. One of the informants, from whom I recorded c. 900 words and 530 sentences, was used as the main data source for the analysis. First, I will give some ethnographic background information on the people who speak Denjongka. Next, I will discuss first the segmental and then the suprasegmental phonology of the language, which were analysed much in line with American structuralism. I also used acoustic analysis enabled by the Praat-program. Eight vowel phonemes were found. The phonemic status of /E/, however, is still suspect. I present some preliminary evidence for roundedness, frontness and height assimilation among the vowels. In the interpretation adopted in this analysis, there are no diphthongs in Denjongka. Forty consonant phonemes were found: 17 plosives, 7 affricates, 5 fricatives, 5 nasals, 4 liquids and 2 approximants. Denjongka plosives and affricates have four-way aspiration/voicing distinction: voiceless aspirated, voiceless unaspirated, voiceless slightly aspirated (devoiced), and voiced unaspirated. Two voiceless nasals and two voiceless liquids were found. Two phonation types were found to be contrastive, lax/breathy and tense/creaky. Nasalisation and length in vowels are phonemic. Denjongka is an incipient tone language. Tonal phenomena, which involve mainly pitch and phonation type, are complex. Pitch is most of the time predictable from the initial consonant and the phonation type. In some cases, however, pitch is the only contrastive feature between words. The description of Denjongka in this paper differs from the traditional four-tone system, which has been used in many descriptions of Tibetan-related languages. In the four-tone system, pitch is contrastive both in the high and low register, whereas in the present analysis pitch has been established to contrast only in the high register. Lastly, the appendices include a comparative word list of the four Denjongka dialects studied in this thesis.
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This study analyses British military planning and actions during the Suez Crisis in 1956. It seeks to find military reasons for the change of concepts during the planning and compares these reasons with the tactical doctrines of the time. The thesis takes extensive advantage of military documents preserved in the National Archives, London. In order to expand the understanding of the exchange of views during the planning process, the private papers of high ranking military officials have also been consulted. French military documents preserved in the Service Historique de la Defence, Paris, have provided an important point of comparison. The Suez Crisis caught the British armed forces in the middle of a transition phase. The main objective of the armed forces was to establish a credible deterrence against the Soviet Union. However, due to overseas commitments the Middle East playing a paramount role because of its economic importance the armed forces were compelled to also prepare for Limited War and the Cold War. The armed forces were not fully prepared to meet this demand. The Middle Eastern garrison was being re-organised after the withdrawal from the Canal Base and the concept for a strategic reserve was unimplemented. The tactical doctrines of the time were based on experiences from the Second World War. As a result, the British view of amphibious operations and the subsequent campaigns emphasised careful planning, mastery of the sea and the air, sufficient superiority in numbers and firepower, centralised command and extensive administrative preparations. The British military had realized that Nasser could nationalise the Suez Canal and prepared an outline plan to meet this contingency. Although the plan was nothing more than a concept, it was accepted as a basis for further planning when the Canal was nationalised at the end of July. This plan was short-lived. The nominated Task Force Commanders shifted the landing site from Port Said to Alexandria because it enabled faster expansion of the bridgehead. In addition, further operations towards Cairo the hub of Nasser s power would be easier to conduct. The operational concept can be described as being traditional and was in accordance with the amphibious warfare doctrine. This plan was completely changed at the beginning of September. Apparently, General Charles Keightley, the Commander-in-Chief, and the Chairman of the Chiefs of Staff Committee developed the idea of prolonged aerial operations. The essence of the concept was to break the Egyptian will to resist by attacking the oil facilities, the transportation system and the armed forces. This victory through air concept would be supported by carefully planned psychological operations. This concept was in accordance with the Royal Air Force doctrine, which promoted a bomber offensive against selected target categories. General Keightley s plan was accepted despite suspicions at every planning level. The Joint Planning Staff and the Task Force Commanders opposed the concept from the beginning to the end because of its unpredictability. There was no information that suggested the bombing would persuade the Egyptians to submit. This problem was worsened by the fact that British intelligence was unable to provide reliable strategic information. The Task Force Commanders, who were responsible for the tactical plans, were not able to change Keightley s mind, but the concept was expanded to include a traditional amphibious assault on Port Said due to their resistance. The bombing campaign was never tested as the Royal Air Force was denied authorisation to destroy the transportation and oil targets. The Chiefs of Staff and General Keightley were too slow to realise that the execution of the plan depended on the determination of the Prime Minister. However, poor health, a lack of American and domestic support and the indecisiveness of the military had ruined Eden s resolve. In the end, a very traditional amphibious assault, which was bound to succeed at the tactical level but fail at the strategic level, was launched against Port Said.
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The purpose of this study is to find a framework for a holistic approach to, and form a conceptual toolbox for, investigating changes in signs and in their interpretation. Charles S. Peirce s theory of signs in a communicative perspective is taken as a basis for the framework. The concern directing the study is the problem of a missing framework in analysing signs of visual artefacts from a holistic perspective as well as that of the missing conceptual tools. To discover the possibility of such a holistic approach to semiosic processes and to form a conceptual toolbox the following issues are discussed: i) how the many Objects with two aspects involved in Peirce s definition of sign-action, promote multiple semiosis arising from the same sign by the same Interpretant depending on the domination of the Objects; ii) in which way can the relation of the individual and society or group be made more apparent in the construction of the self since this construction is intertwined with the process of meaning-creation and interpretation; iii) how to account for the fundamental role of emotions in semiosis, and the relation of emotions with the often neglected topic of embodiment; iv) how to take into account the dynamic, mediating and processual nature of sign-action in analysing and understanding the changes in signs and in the interpretation of signs. An interdisciplinary approach is chosen for this dissertation. Concepts that developed within social psychology, developmental psychology, neurosciences and semiotics, are discussed. The common aspect of the approaches is that they in one way or another concentrate on mediation provided by signs in explaining human activity and cognition. The holistic approach and conceptual toolbox found are employed in a case study. This consists of an analysis of beer brands including a comparison of brands from two different cultures. It becomes clear that different theories and approaches have mutual affinities and do complement each other. In addition, the affinities in different disciplines somewhat provide credence to the various views. From the combined approach described, it becomes apparent that by the semiosic process, the emerging semiotic self intertwined with the Umwelt, including emotions, can be described. Seeing the interpretation and meaning-making through semiosis allows for the analysis of groups, taking into account the embodied and emotional component. It is concluded that emotions have a crucial role in all human activity, including so-called reflective thinking, and that emotions and embodiment should be consciously taken into account in analysing signs, the interpretation, and in changes of signs and interpretations from both the social and individual level. The analysis of the beer labels expresses well the intertwined nature of the relationship between signs, individual consumers and society. Many direct influences from society on the label design are found, and also some indirect attitude changes that become apparent from magazines, company reports, etc. In addition, the analysis brings up the issues of the unifying tendency of the visual artefacts of different cultures, but also demonstrates that the visual artefacts are able to hold the local signs and meanings, and sometimes are able to represent the local meanings although the signs have changed in the unifying process.
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The number of immigrant students in vocational education and training is steadily increasing in Finland. This poses challenges for teachers and schools. This research focuses on emerging questions of intercultural learning in the context of immigrant training, and on a method the Culture Laboratory that was developed in an attempt to respond to the challenges. The main methodological and theoretical framework lies in cultural-historical activity theory, developmental work research, and in the concepts of the intercultural and hybridity. The empirical material consists of videotaped recordings of discussions in the Culture Laboratory. The five main research questions focused on the strengths and limitations of the Culture Laboratory as a tool for intercultural learning, the significance of disturbances in it, the potential of suggestions for intercultural learning, paper as a mediating artifact , and the concept of intercultural space. The findings showed that the Culture Laboratory offered a solid background for developing intercultural learning. The disturbances manifested revealed a multitude of scripts and activities. It was also suggested that the structure of expansive learning could start from externalization instead of internalization. The suggestions the participants made opened up a hybrid learning space for intercultural development, and offered a good springboard for new ideas. Learning in Paperland posed both challenges and opportunities for immigrant students, and different paper trails emerged. Intercultural space in the Culture Laboratory was a developmental zone in which a hybrid process of observing, comparing, and creating took place. Key words: intercultural learning, immigrant training, cultural-historical activity theory, developmental work research,
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The early detection of hearing deficits is important to a child's development. However, examining small children with behavioural methods is often difficult. Research with ERPs (event-related potentials), recorded with EEG (electroencephalography), does not require attention or action from the child. Especially in children's ERP research, it is essential that the duration of a recording session is not too long. A new, faster optimum paradigm has been developed to record MMN (mismatch negativity), where ERPs to several sound features can be recorded in one recording session. This substantially shortens the time required for the experiment. So far, the new paradigm has been used in adult and school-aged children research. This study examines if MMN, LDN (late discriminative negativity) and P3a components can be recorded in two-year-olds with the new paradigm. The standard stimulus (p=0.50) was an 80 dB harmonic tone consisting of three harmonic frequencies (500 Hz, 1000 Hz and 1500 Hz) with a duration of 200 ms. The loudness deviants (p=0.067) were at a level of +6 dB or -6 dB compared to the standards. The frequency deviants (p=0.112) had a fundamental frequency of 550 or 454.4 Hz (small deviation), 625 or 400 Hz (medium deviation) or 750 or 333.3 Hz (large deviation). The duration deviants (p=0.112) had a duration of 175 ms (small deviation), 150 ms (medium deviation) or 100 ms (large deviation). The direction deviants (p=0.067) were presented from the left or right loudspeaker only. The gap deviant (p=0.067) included a 5-ms silent gap in the middle of the sound. Altogether 17 children participated in the experiment, of whom the data of 12 children was used in the analysis. ERP components were observed for all deviant types. The MMN was significant for duration and gap deviants. The LDN was significant for the large duration deviant and all other deviant types. No significant P3a was observed. These results indicate that the optimum paradigm can be used with two-year-olds. With this paradigm, data on several sound features can be recorded in a shorter time than with the previous paradigms used in ERP research.
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The purpose of this research was to evaluate the special vocational training programme, which aimed at enhancing the pupils with autism spectrum to prepare themselves for work and independent life. The vocational training programme is based on TEACCH (Treatment and Education of Autistic and Related Communication handicapped CHildren), which takes into account the autism spectrum disorders and autistic behaviour. TEACCH is based on the principles of structured teaching, functional teaching and preparation training for work and independent life. The TEACCH has been adapted to Finnish society and the educational system. Treatment programmes were individually designed for each student´s educational needs. There is also an important role for the AAPEP rating scale (Adolescent and Adult Psychoeducational Profile). The AAPEP has been the major tool for planning and following the courses. The AAPEP is an assessment instrument designed by the TEACCH programme, and it is used to provide an evaluation of current and potential skills. The AAPEP contains three scales: a direct observation scale, a home scale and a school / work scale. The AAPEP includes six test variables: vocational skills, independent functions, functional communication, interpersonal behaviour, vocational behaviour and leisure skills; these are evaluated at three levels: pass, emerge and fail. The subjects were 49 students (65% male and 35 % female) with autism spectrum, who have been followed and tested several times, also one year after the vocational training. The design is therefore a longitudinal one. The research data were collected 1997-2004 using the AAPEP rating scales. The teachers have used the AAPEP scales and the codings have been checked by the researcher. The results of the principal component analysis (PCA) suggested that the structure of AAPEP rating scales works quite well as a hypothesis. The factor structure of the scales of the AAPEP was almost the same in these data as in the original publications. The learning-and-changes results showed that learning is a slow process, but that there were also intended changes in several AAPEP areas. The Cohen´s kappa was used as an effect-size measure and the most important result of this research showed that the student´s skills were developing on a school / work scale; vocational skills variable (0,34), vocational behaviour variable (0,28), leisure skills variable (0,26) and on a direct observation scale; interpersonal behaviour variable (0,21). On a home scale skills of some students were developing negatively and also that effect-size was small. The results showed that the students´ vocational skills and vocational behaviour will continue to develop after school in many areas. There were differences between scales. The result of this research shows that the student´s skills were developing significantly in 3 of 48 variables on a direct observation scale and also on a home scale. On a school / work scale student´s skills were developing significantly in 17 of 48 variables. This result implies that students can do the work without extra assistance if there exist continuing supports for the skills after the vocational training. The fully independent life of students will be difficult, because their independent functions, functional communications and leisure skills regressed after the schooling. This seems to indicate that they will not manage their daily life without support. The students and their parents said that the treatment programmes were individually designed for each student s educational needs, and that they were satisfied with the programmes and services. Generally, it can be concluded that vocational special education can be developed for pupils with autistic syndrome and the detailed teaching can be done using TEACCH principles and applying the tool of AAPEP.
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Bovine serum albumin conjugates of two trinucleotides, dpTpTpA and dTpTpAp, were prepared by linking the trinucleotides through their end phosphates by the ‘carbodiimide method’. Antibodies were raised in rabbits by injecting the trinucleotide-bovine serum albumin conjugates. Analysis by double diffusion in agar gel, quantitative precipitin reaction and its inhibition by haptens showed clearly the presence of antibodies specific to the whole trinucleotide molecule. The titre of antibodies obtained by the trinucleotide-rabbit serum albumin conjugates with their respective antisera was approximately the same, indicating that linking the trinucleotide through either 5′ or 3′ phosphate does not have an appreciable effect on the titre of antibodies. The results also demonstrate that the nucleotide(s) away from the carrier protein is more immunodominant than the one linked directly to the protein.
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The goal of this research was to survey the self-concept and school achievement of pupils with cleft lip, cleft palate or both from juvenile age to adolescence. Longitudinal researches of self-concept and school achievement among pupils with cleft lip, cleft palate or both are uncommon. This research was the first longitudinal research ever conducted in Finland among this population. This research can be considered to be a special educational study because of the target group involved. Self-concept consists of the person s entire personality. Personality is biological and deterministic. Self-concept includes concepts, attitudes and feelings that the person has about him or her qualities, abilities and relations to the environment. The individual associates experiences to this personality with earlier observations through the social interaction. The individual will have the consciousness of the person s existence and action. The target group in this study consisted of Finnish children with clefts, who were comprised of four different age groups. The questionnaire was sent to all subjects (N1 = 419) both times. A total of 74 % of children returned the questionnaire in 1988 (N2=305). 48 % of children returned the questionnaire in 1993 (N3=203). 42% of children returned the questionnaire both times (N4=175) . These 175 children formed the research subjects. The survey was conducted in 1988, and again in 1993. In 1988, the pupils surveyed were 9 to 12 years of age, while in 1993 they were between 14 and 17 years old. The data was collected through the use of a questionnaire, which consisted of common questions and a personality inventory test that was developed for Finnish students by professor Maija-Liisa Rauste-von Wright. Quantitative analysis methods were used to examine the structure of self-concept and school achievement. Structures found in this research were observed in relation to disorder, gender and maturation. According to these results, structures of self-concepts and school achievement are in fact stable. Basic self-concept elements are seen to be formed at an early age. The developmental aspects of self-concept following puberty are observed as the stability of self-concept and as the forming of a general self. The level of school achievement is stable, but the structure of school achievement changes. From these results, it is possible to state that the gender of the child has a statistical significance regarding self-concept and school achievement. However, the experienced disorder does not have statistical significance as regards to self-concept and school achievement. Results of self-concept support the research of self-concept conducted earlier in Finland.
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The aim of this study was to explore the spirituality of Finnish academically gifted 12 13-year old pre-adolescents (N = 101). Their spirituality was investigated through the following three questions: (1) What is their relationship to religion? (2) How do they perceive transcendence? and (3) How does their search for meaning integrate into their lives? A total of 60 girls and 41 boys participated in the study. They attend a special school, Helsingin Suomalainen yhteiskoulu, in Helsinki, Finland. The school includes classes from grade 3 to upper secondary school and has an entrance test. This study is part of a research project called Actualizing Finnish Giftedness which is funded by the Finnish Academy between 2000 2007 and is led by Professor Tirri. The research project is based on Gardner s Multiple Intelligences theory (Gardner 1993) and on Hay s (1998) work on spirituality. The data in this study was gathered in 2003 and 2004. It includes both qualitative and quantitative material. The emphasis is on data gathered with interviews. The mixed method approach was used as the methodological framework for connecting the qualitative content analysis, phenomenological approach and the quantitative tests of this study. The results of the sub-studies are reported in full in the four original articles. First, the articles show that the pupils connect religion mainly with Christian institutions and do not consider religion and spirituality to overlap. Second, the articles show that the pupils believe in God and the interference of God in their lives and they think that reality includes a spiritual dimension. Third, the pupils had four kinds of existentially significant interests: personal, transcendental, cosmic and ethical. Cosmic interests were especially highlighted in the article concerning boys as nature and science were reported to be integral sources for their existential thinking. In addition, perceptions on God seemed to be connected to the individual s perception on the meaning of life. In RE, spiritual development has been a constant topic of interest since the late eighties. Likewise, recently in gifted education there have been discussions concerning spiritual intelligence (Gardner 1999) and spirituality of the gifted (Kerr & Cohn 2001). Based on the empirical results of the study, this study concludes that education wishing to promote spiritual development should aim at being existentially relevant to the pupils and use their existential search as an integrative framework for their individual talents and skills.