Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

The contribution of individual and professional characteristics to general and work-related well-being

Cette thèse porte sur la contribution des caractéristiques individuelles et des situations professionnelles au bien-être. En combinant différentes perspectives théoriques, notamment la théorie de la construction de la carrière, la théorie de la justice organisationnelle, les modèles du bien-être au travail, et les conceptualisations de l'incivilité au travail, un certain nombre d'hypothèses sont proposées concernant le lien entre certaines caractéristiques individuelles et situationnelles et le bien-être général et professionnel. Les deux premières études se focalisent sur la validation d'une échelle d'adaptabilités de carrière et sur le rôle médiateur de cette adaptabilité dans la relation entre des dispositions et le bien-être. La troisième étude évolue l'hypothèse d'un possible effet de médiation de l'adaptabilité mais cette fois de la relation entre insécurité professionnelle et charge de travail d'une part et le bien-être d'autre part. La quatrième étude adopte une perspective longitudinale et analyse les associations entre les dimensions de la personnalité, l'adaptabilité de carrière et le bien-être dans quatre parcours professionnels différents. La cinquième étude porte sur une autre caractéristique individuelle, à savoir la croyance en un monde juste. Cette étude illustre comment la croyance en un monde juste influence les perceptions de justice organisationnelle une année après, qui ont une incidence importante sur le bien-être. Enfin, la dernière étude se concentre sur une population spécifique, les immigrants en Suisse, et souligne qu'être la cible d'incivilité sur le lieu de travail est généralement liée au pays d'origine. Globalement, cette thèse met en évidence que les caractéristiques individuelles ont des effets tant directs qu'indirects sur le bien-être et que ces mêmes caractéristiques explique en partie, les relations entre la situation professionnelle et le bien-être. Plus spécifiquement, des situations professionnelles peuvent influencer l'expression de certaines caractéristiques individuelles, soit en contribuant à leurs activations ou à leurs inhibitions. De plus, l'impact des caractéristiques individuelles sur le bien-être semble dépendre de la situation professionnelle. Il est donc important de considérer les influences simultanées et réciproques des caractéristiques individuelles et de la situation contextuelle et professionnelle pour rendre compte du bien-être général et professionnel. -- This thesis explores how individual characteristics and professional situations correspond to well-being. Drawing from various theoretical backgrounds, such as career construction theory, justice theory, models of job strain, and theories on subtle discrimination, a number of specific hypotheses are put forward pertaining to a selection of individual and professional aspects as well as general and work-related well-being. The six studies presented in this thesis focus on specific aspects and adopt different methodological and theoretical approaches. The first two studies concern the validation of the career adapt-abilities scale and test the potential of career adapt-abilities to mediate the relationship between dispositions and outcomes. The third study extends the hypothesis of career adapt-abilities as a mediator and finds that it mediates the effects of job insecurity and job strain on general and professional well-being. The fourth study adopts a longitudinal approach and tests the associations between personality traits and career adaptability and well-being in four different professional situations. Study five concerns another individual characteristic, belief in a just world, and illustrates how justice beliefs drive perceptions of organizational justice, which in turn impact, on well-being outcomes one year later. The final study focuses on the professional experiences of a specific population, immigrants in Switzerland, and confirms that being a target of incivilities is related to national origin. Globally, this thesis finds that individual characteristics have direct and indirect influences on well-being and that these characteristics may also mediate the associations between professional situations and outcomes. In particular, the professional situation may alter the display of individual characteristics, either by contributing to their activation or their depletion, and the ways in which individual factors influence well-being does seem to depend on the professional situation. It is thus necessary to adopt a "both...and" perspective when studying the impact of individual and professional characteristics as these factors mutually influence each other.

Local effects and global impact in neurotoxicity and neurodegeneration: The Xi"an International Neurotoxicology Conference

'Neurotoxicity and Neurodegeneration: Local Effect and Global Impact' was the theme of the Xi"an International Neurotoxicology Conference (XINC), held in Xi"an, June 2011. The Conference was a joint event of the 13th Biennial Meeting of the International Neurotoxicology Association (INA-13) and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health (NEUREOH-11) of the Scientific Committee on Neurotoxicology and...

Neuropeptide Y at the cellular level – Studies on PreproNPY L7P Polymorphism and the Mitochondrial Form of NPY

Neuropeptide Y (NPY) is a widely expressed neurotransmitter in the central and peripheral nervous systems. Thymidine 1128 to cytocine substitution in the signal sequence of the preproNPY results in a single amino acid change where leucine is changed to proline. This L7P change leads to a conformational change of the signal sequence which can have an effect on the intracellular processing of NPY. The L7P polymorphism was originally associated with higher total and LDL cholesterol levels in obese subjects. It has also been associated with several other physiological and pathophysiological responses such as atherosclerosis and T2 diabetes. However, the changes on the cellular level due to the preproNPY signal sequence L7P polymorphism were not known. The aims of the current thesis were to study the effects of the [p.L7]+[p.L7] and the [p.L7]+[p.P7] genotypes in primary cultured and genotyped human umbilical vein endothelial cells (HUVEC), in neuroblastoma (SK-N-BE(2)) cells and in fibroblast (CHO-K1) cells. Also, the putative effects of the L7P polymorphism on proliferation, apoptosis and LDL and nitric oxide metabolism were investigated. In the course of the studies a fragment of NPY targeted to mitochondria was found. With the putative mitochondrial NPY fragment the aim was to study the translational preferences and the mobility of the protein. The intracellular distribution of NPY between the [p.L7]+[p.L7] and the [p.L7]+[p.P7] genotypes was found to be different. NPY immunoreactivity was prominent in the [p.L7]+[p.P7] cells while the proNPY immunoreactivity was prominent in the [p.L7]+[p.L7] genotype cells. In the proliferation experiments there was a difference in the [p.L7]+[p.L7] genotype cells between early and late passage (aged) cells; the proliferation was raised in the aged cells. NPY increased the growth of the cells with the [p.L7]+[p.P7] genotype. Apoptosis did not seem to differ between the genotypes, but in the aged cells with the [p.L7]+[p.L7] genotype, LDL uptake was found to be elevated. Furthermore, the genotype seemed to have a strong effect on the nitric oxide metabolism. The results indicated that the mobility of NPY protein inside the cells was increased within the P7 containing constructs. The existence of the mitochondria targeted NPY fragment was verified, and translational preferences were proved to be due to the origin of the cells. Cell of neuronal origin preferred the translation of mature NPY (NPY1-36) when compared to the non neuronal cells that translated both, NPY and the mitochondrial fragment of NPY. The mobility of the mitochondrial fragment was found to be minimal. The functionality of the mitochondrial NPY fragment remains to be investigated. L7P polymorphism in the preproNPY causes a series of intracellular changes. These changes may contribute to the state of cellular senescence, vascular tone and lead to endothelial dysfunction and even to increased susceptibility to diseases, like atherosclerosis and T2 diabetes.

Labour segregation and immigrant and native-born wage distributions in Spain: an analysis using matched employer-employee data

This article carries out an empirical examination of the origin of the differences between immigrant and native-born wage structures in the Spanish labour market. Especial attention is given in the analysis to the role played by occupational and workplace segregation of immigrants. Legal immigrants from developing countries exhibit lower mean wages and a more compressed wage structure than native-born workers. By contrast, immigrants from developed countries display higher mean wages and a more dispersed wage structure. The main empirical finding is that the disparities in the wage distributions for the native-born and both groups of immigrants are largely explained by their different observed characteristics, with a particularly important influence in this context of workplace and, particularly, occupational segregation.

Ammatillisen osaamisen tukeminen muuttuvissa toimintaympäristöissä : tutkimus ikääntyvien työntekijöiden näkökulmasta

The purpose of the study was to describe the experiences of received support of aging employees and their work related self-image in changing working environments. Firstly, theaim was to discover how the support from organisations and leaders was verified. Secondly, the aim was to get answers how employees experienced themselves as workers and as learners in the current work context. Thirdly, the aim was to compare different knowledge information stages and company cultures and how they have influenced the experiences of professional competence development among aging employees. In addition the education- and career backgrounds were investigated to gain more understanding of their role in experiencing support and relation to the occupational self-image. The theoretical frame of reference of this researchis multidisciplinary. The theoretical part focuses on the meaning of work for human being from a sociological, late-modern perspective. On the other hand it examines the ageing process from a physiological and also from a perspective of age discrimination and life control. The occupational selfimage and the strength of motivation has an effect on learning in working life which is crucial and firmpart individual trajectories. According to the theoretical review company culture, leadership and especially the managers' role as a creator of a learning atmosphere are increasingly critical for aging adults' learning when the role of informal work-based learning is increasing. The empirical data was collected with aquestionnaire and interviews, which were carried out in May to October 2001. The data consists of 263 respondents of which further eight persons were interviewed. All respondents were over the age of 45 and represented all levels of their organisations in an IT-technology firm and a chemical industry plant. The central findings in this research show that the aging adults have experienced that theemployers do care about the development of their occupational skills. On the other hand there are fewer concrete activities to reveal this support. There is anobvious disproportion between the expressed aims and the realisation of the activities. Signs of age discrimination are few. The style of management has becomemore supporting for self directed activities which are seen to support adults learning. Higher education and individual activity to seek possibilities to learnwere encouraging the development of occupational skills. Age itself was not a crucial aspect when comparing the experiences among younger (45-54 years) and older (55-64 years) groups. Job satisfaction and professional self esteem seemed tobe considerably strong. The individual characteristics were more important elements in developing occupational skills than the age. The degree of anxiety at work was low. In addition among the older group the strong feeling of coherence and the occupational self image were significant for supporting the professional competence. The motivation to learn was also stable. Among the seniors there was some slight evidence of declining motivation. In the IT-firm the support was experienced stronger for aging employees than in the chemical industry plant. Thosewho had experienced support in the chemical industry plant had higher educational background than the others. In IT-firm they also experienced more support from the manager than in the chemical industry plant. The results show that it is more likely that the differences are caused mostly by the stage of information intensity and the character of company culture which is determined by the activities. IT-business demands constantly accommodation to changes and the chemical industry plant which is representing more traditional business field, where the atmosphere of learning is determined by the traditions of company culture, the changes are carried out slowly.

Conference Proceedings. Academic Mobility Blending Perspectives - Mobilité Académique Perspectives croisées

Les 21, 22 et 23 septembre 2006, le Département d’Études Françaises de l’Université de Turku (Finlande) a organisé une conférence internationale et bilingue (anglais et français) sur le thème de la mobilité académique ; le but de cette rencontre était de rendre possible la tenue d’un forum international et multidisciplinaire, susceptible d’être le siège de divers débats entre les différents acteurs de la mobilité académique (c’estàdire des étudiants, des chercheurs, des personnels enseignants et administratifs, etc.). Ainsi, ont été mis à contribution plus de cinquante intervenants, (tous issus de domaines aussi variés que la linguistique, les sciences de l’éducation, la didactique, l’anthropologie, la sociologie, la psychologie, l’histoire, la géographie, etc.) ainsi que cinq intervenants renommés1. La plupart des thèmes traités durant la conférence couvraient les champs suivants : l’organisation de la mobilité, les obstacles rencontrés par les candidats à la mobilité, l’intégration des étudiants en situation d’échange, le développement des programmes d’études, la mobilité virtuelle, l’apprentissage et l’enseignement des langues, la prise de cosncience interculturelle, le développement des compétences, la perception du système de mobilité académique et ses impacts sur la mobilité effective. L’intérêt du travail réalisé durant la conférence réside notamment dans le fait qu’il ne concentre pas uniquement des perspectives d’étudiants internationaux et en situation d’échange (comme c’est le cas de la plupart des travaux de recherche déjà menés sur ce sujet), mais aussi ceux d’autres corps : enseignants, chercheurs, etc. La contribution suivante contient un premier corpus de dixsept articles, répartis en trois sections : 1. Impacts de la mobilité étudiante ; 2. Formation en langues ; 3. Amélioration de la mobilité académique. À l’image de la conférence, la production qui suit est bilingue : huit des articles sont rédigés en français, et les neuf autres en anglais. Certains auteurs n’ont pas pu assister à la conférence mais ont tout de même souhaité apparaître dans cet ouvrage. Dans la première section de l’ouvrage, Sandrine Billaud tâche de mettre à jour les principaux obstacles à la mobilité étudiante en France (logement, organisation des universités, démarches administratives), et propose à ce sujet quelques pistes d’amélioration. Vient ensuite un article de Dominique Ulma, laquelle se penche sur la mobilité académique régnant au sein des Instituts Universitaires de Formation des Maîtres (IUFM) ; elle s’est tout particulièrement concentrée sur l’enthousiasme des stagiaires visàvis de la mobilité, et sur les bénéfices qu’apporte la mobilité Erasmus à ce type précis d’étudiant. Ensuite, dans un troisième article, Magali Hardoin s’interroge sur les potentialités éducationnelles de la mobilité des enseignantsstagiaires, et tâche de définir l’impact de celleci sur la construction de leur profil professionnel. Après cela arrive un groupe de trois articles, tous réalisés à bases d’observations faites dans l’enseignement supérieur espagnol, et qui traitent respectivement de la portée qu’a le programme de triple formation en langues européennes appliquées pour les étudiants en mobilité (Marián MorónMartín), des conséquences qu’occasionne la présence d’étudiants étrangers dans les classes de traductions (Dimitra Tsokaktsidu), et des réalités de l’intégration sur un campus espagnol d’étudiants américains en situation d’échange (Guadalupe Soriano Barabino). Le dernier article de la section, issu d’une étude sur la situation dans les institutions japonaises, fait état de la situation des programmes de doubles diplômes existant entre des établissements japonais et étrangers, et tente de voir quel est l’impact exact de tels programmes pour les institutions japonaises (Mihoko Teshigawara, Riichi Murakami and Yoneo Yano). La seconde section est elle consacrée à la relation entre apprentissage et enseignement des langues et mobilité académique. Dans un premier article, Martine Eisenbeis s’intéresse à des modules multimédia réalisés à base du film « L’auberge espagnole », de Cédric Klapish (2001), et destinés aux étudiants en mobilité désireux d’apprendre et/ou améliorer leur français par des méthodes moins classiques. Viennent ensuite les articles de Jeanine Gerbault et Sabine Ylönen, lesquels traitent d’un projet européen visant à supporter la mobilité étudiante par la création d’un programme multimédia de formation linguistique et culturelle pour les étudiants en situation de mobilité (le nom du projet est EUROMOBIL). Ensuite, un article de Pascal Schaller s’intéresse aux différents types d’activités que les étudiants en séjour à l’étranger expérimentent dans le cadre de leur formation en langue. Enfin, la section s’achève avec une contribution de Patricia KohlerBally, consacrée à un programme bilingue coordonné par l’Université de Fribourg (Suisse). La troisième et dernière section propose quelques pistes de réflexion destinées à améliorer la mobilité académique des étudiants et des enseignants ; dans ce cadre seront donc évoquées les questions de l’égalité face à la mobilité étudiante, de la préparation nécessitée par celleci, et de la prise de conscience interculturelle. Dans un premier chapitre, Javier Mato et Bego

Entrepreneurial orientation in small and medium-sized enterprises during economic crisis

The economic importance of small and medium-sized enterprises (SMEs) and entrepreneurship has increased significantly in recent decades and entrepreneurial activity and SMEs are deemed vital to economic progress. Therefore, it is justifiable to study how small firms and entrepreneurs can enhance their performance and emergence in the turbulent economic environment. The concept of entrepreneurial orientation (EO) has recently attracted considerable attention in the field of entrepreneurship research. EO generally refers to a firm’s propensity to be innovative, to be proactive and to take risks. A majority of EO studies so far have found that adopting EO associated entrepreneurial behaviors will help firms to create or sustain a high level of performance. This dissertation explores the main drivers and performance implications of EO for SMEs in time of economic crisis. Hence the first objective of this dissertation is to examine the performance implications of EO and to test the role of EO on how firms are treated by the crisis at operative level. The second objective is to expand the prevailing understanding of determinants of EO by exploring the relationship between owner's work related values, attitudes, demographic characteristics, firm’s financial resources and EO. EO was found to be a significant and positive factor behind a firm’s long run growth. Hence it can be said that EO has positive implications for firm performance. But on the other hand, during a time of economic crisis the different dimensions of EO had both positive and negative effects on performance of SMEs. The performance implications varied across different stages of the crisis and were also dependent on what measure was used for measuring the performance. The main drivers of EO in SMEs were the personal work related values of the entrepreneur and his/her prior experience as an entrepreneur. The intrinsic work values related to interest, responsibility, challenge, self-development or intellectual stimulation and values related to status, power, achievement and recognition had a positive effect on the level of EO. On the other hand, extrinsic values related to high income, material possessions, benefits such as generous holidays, job security, and comfort through good working conditions decreased the level of EO

Limits of Meritocracy. How Fields of Study and Gender Segregation Affect Social Stratification in Finland

This dissertation critically reviews the idea of meritocracy from both a theoretical and an empirical perspective. Based on a discussion of classical texts of social philosophy and sociology, it is argued that meritocracy as a concept for social stratification is best compatible with the sociological tradition of status attainment research: both frame social inequality in primarily individualistic terms, centring on the role of ascribed (e.g., gender, social background) and achieved (e.g., educational qualifications) characteristics for determining individuals’ socioeconomic rewards. This theoretical argument introduces the research problem at the core of this dissertation: to what extent can the individualistic conception of social stratification be maintained empirically? Fields of study and their interaction with educational attainment levels play a prominent role in the analysis of this question. Drawing on sociological versions of segmented labour market theory, it is assumed that fields of study may channel individuals into heterogeneous political-economic contexts on the labour market, which potentially modify the socioeconomic benefit individuals derive from their qualification levels. The focus on fields of study may also highlight economic differentials between men and women that derive from the persisting segregation of men’s and women’s occupational and educational specializations rather than direct gender discrimination on the labour market. The quantitative analyses in this dissertation consist of three research articles, which are based primarily on Finnish data, but occasionally extend the view to other European countries. The data sources include register-based macro- and microdata as well as survey data. Article I examines the extent and the patterns of gender segregation within the Finnish educational system between 1981 and 2005. The results show that differences between men’s and women’s field specializations have for the most part remained stable during this period, with particularly high levels of gender segregation observed at lower educational levels. The focus in Article II rests on the effects of gender-segregated fields of study on higher education graduates’ occupational status. It is shown that fields of study matter for accessing professional jobs and avoiding low-skilled positions in Finland: at the early career stage, particularly polytechnic graduates from female-dominated fields are less likely to work in professional positions. Finnish university graduates from male-dominated fields were more likely than their peers with different specializations to work as professionals, yet they also faced a greater risk of being sorted into lowskilled jobs if they failed to make use of this advantage. Article III proceeded to analyse the joint impact of educational qualification levels and fields of study on young adults’ median earnings in Finland between 1985 and 2005. The results show that qualification levels do not confer a consistent benefit in the process of earnings stratification. Advanced qualifications raise median earnings most clearly among individuals specializing in the same field of study. When comparing individuals with different field specializations, on the other hand, higher-level qualifications do not necessarily lead to higher median earnings. Overall, the findings of this dissertation reveal a heterogeneous effect of education for achieving social positions, which challenges individual-centred, meritocratic accounts of social stratification and underlines the problematic lack of structural and institutional dimensions in the dominant account of social status attainment.