Viral-mediated overexpression of mutant huntingtin to model HD in various species.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin (Htt) gene. Despite intensive efforts devoted to investigating the mechanisms of its pathogenesis, effective treatments for this devastating disease remain unavailable. The lack of suitable models recapitulating the entire spectrum of the degenerative process has severely hindered the identification and validation of therapeutic strategies. The discovery that the degeneration in HD is caused by a mutation in a single gene has offered new opportunities to develop experimental models of HD, ranging from in vitro models to transgenic primates. However, recent advances in viral-vector technology provide promising alternatives based on the direct transfer of genes to selected sub-regions of the brain. Rodent studies have shown that overexpression of mutant human Htt in the striatum using adeno-associated virus or lentivirus vectors induces progressive neurodegeneration, which resembles that seen in HD. This article highlights progress made in modeling HD using viral vector gene transfer. We describe data obtained with of this highly flexible approach for the targeted overexpression of a disease-causing gene. The ability to deliver mutant Htt to specific tissues has opened pathological processes to experimental analysis and allowed targeted therapeutic development in rodent and primate pre-clinical models.

Pedotransfer functions to estimate retention and availability of water in soils of the state of Santa Catarina, Brazil

Studies on water retention and availability are scarce for subtropical or humid temperate climate regions of the southern hemisphere. The aims of this study were to evaluate the relations of the soil physical, chemical, and mineralogical properties with water retention and availability for the generation and validation of continuous point pedotransfer functions (PTFs) for soils of the State of Santa Catarina (SC) in the South of Brazil. Horizons of 44 profiles were sampled in areas under different cover crops and regions of SC, to determine: field capacity (FC, 10 kPa), permanent wilting point (PWP, 1,500 kPa), available water content (AW, by difference), saturated hydraulic conductivity, bulk density, aggregate stability, particle size distribution (seven classes), organic matter content, and particle density. Chemical and mineralogical properties were obtained from the literature. Spearman's rank correlation analysis and path analysis were used in the statistical analyses. The point PTFs for estimation of FC, PWP and AW were generated for the soil surface and subsurface through multiple regression analysis, followed by robust regression analysis, using two sets of predictive variables. Soils with finer texture and/or greater organic matter content retain more moisture, and organic matter is the property that mainly controls the water availability to plants in soil surface horizons. Path analysis was useful in understanding the relationships between soil properties for FC, PWP and AW. The predictive power of the generated PTFs to estimate FC and PWP was good for all horizons, while AW was best estimated by more complex models with better prediction for the surface horizons of soils in Santa Catarina.

Diagnosis and management of blunt great vessel trauma.

Traditionally, thoracic aortic rupture, suspected after blunt thoracic trauma, is characterized by a chest radiograph showing a widened mediastinum. The diagnostic machinery consecutively activated still depends heavily on the pressure as additional traumatic lesions. A patient with additional cranio-cerebral trauma would typically undergo contrast-enhanced computed tomography or magnetic resonance imaging of head, chest, and other regions. In a number of patients these analyses would confirm the presence of blood in the mediastinum without formal proof of an aortic disruption. This is because mediastinal hematomas may be caused not only by an aortic rupture, but also by numerous other blood sources including fractures of the spine and other macro- and microvascular lesions providing similar images. Therefore, aortic angiography became our preferred diagnostic tool to identify or rule out acute traumatic lesions of not only the aorta but with great vessels. However recently, a number of traumatic aortic transsections have been identified by transoesophageal echocardiography (TEE). TEE has the additional advantage of being a bed-side procedure providing additional information about cardiac function. The latter analysis allows for identification and quantification of cardiac contusions, post-traumatic myocardial infarctions, and valvar lesions which are of prime importance to develop an adequate surgical strategy and to assess the risk of the numerous emergency procedures required in patients with polytrauma. The standard approach for repair of isthmic aortic rupture is through a lateral thoracotomy. Distal and proximal control of the aorta can be achieved in a substantial number of cases before complete aortic rupture occurs and a higher proportion of direct suture repair can be achieved under such circumstances. Most proximal descending aortic procedures are performed without cardiopulmonary bypass (clamp and go) but paraplegia may occur before, during, or after the procedure. Ascending aortic lesions and disruption of the aortic arch, the supra-aortic vessels, the main pulmonary arteries, the great veins as well as cardiac lesions are best approached through a sternotomy, which may have to be extended. Cardiopulmonary bypass allowing for deep hypothermia and circulatory arrest is often required and carries its own complications. It is not clear whether the increasing proportion of ascending aortic and cardiac lesions which are observed nowadays are due to a change in trauma mechanics (i.e., speed limits, seat belts, air-bags), an improvement of the diagnostic tools or both.

Delivery of European Cross-Border Health Care and the Relevance and Effects of EU Regulations and Judicial Processes with Reference to Delivery of Drugs and Blood Donor Information Material.

Valtion rajat ylittävät terveyspalvelut Euroopan unionissa sekä Euroopan unionin säädösten merkitys ja vaikutus erityisesti lääkejakeluun ja verenluovuttajille jaettavaan tiedotusaineistoon Valtion rajat ylittävä terveydenhuolto on suuren kiinnostuksen kohteena Euroopan unionissa. Resurssien hyödyntäminen parhaalla mahdollisella tavalla ja tiedon keskittäminen ovat tarpeen terveydenhuollon kustannusten alati noustessa. Terveydenhuoltopalvelut kuuluvat Euroopan sisämarkkinoiden vapaan liikkuvuuden piiriin. Euroopan unionilla ei ole kuitenkaan toimivaltaa säädellä terveydenhuoltojärjestelmiä, vaan sen mahdollisuudet ovat enimmäkseen kansanterveyden edistämisessä ja suojelussa, myös muilla toimialueilla kuin terveydenhuollossa. Tutkimuksen tavoitteena oli tutkia Euroopan unionin säädösten vaikutusta terveydenhuoltosektoriin, erityisesti valtion rajat ylittäviin terveydenhuoltopalveluihin. Erityiskohteena olivat lääkemääräyksen toimittaminen toisen Euroopan unionin jäsenmaan apteekista, resepti-lääkkeiden maahantuonti omaan henkilökohtaiseen käyttöön, sähköisen lääkemääräyksen käyttö kansallisesti ja mahdollisuudet sen käyttöön eri jäsenmaiden välillä, online-apteekkien soveltuvuus Euroopan unionin sisämarkkinoille sekä verenluovuttajille jaettavan tiedotusaineiston yhtenäistämistarve Euroopan unionin alueella. Tutkimuksen osa-alueiden aineisto koottiin vuosina 1999–2003, jolloin Euroopan unioniin kuului 15 jäsenmaata. Apteekit toimittivat useimmiten myös ei-kansalliset, toisessa Euroopan unionin jäsenmaassa annetut lääkemääräykset. Kaikki jäsenmaat rajoittivat lääkemääräyksen vaativien lääkkeiden maahantuontia. Rajoituksia oli maahantuontimäärissä ja -tavoissa. Lisäksi sairasvakuutuskorvausten saaminen ulkomailla lunastetuista reseptilääkkeistä oli hankalaa. Sähköiset lääkemääräykset olivat käytössä vain kahdessa maassa, mutta useissa maissa suunniteltiin niiden kokeilua. Standardit ja käyttöjärjestelmät olivat erilaisia eri maissa. Euroopan unionin alueelle on perustettu online-apteekkeja, joiden toiminta on kuitenkin vaatimatonta. Verenluovuttajille annettava tiedotusaineisto ei missään maassa täyttänyt veridirektiivin vaatimuksia. Tutkimuksen tulokset osoittivat kansallisten käytäntöjen eroavaisuuksien rajoittavan valtion rajat ylittäviä terveydenhuoltopalveluita. Vaikka Euroopan unionin tavoitteena ei ole yhtenäistää terveydenhuoltojärjestelmiä, on tarpeen arvioida uudelleen unionin ja jäsenmaiden välistä työnjakoa. Kansalliset terveydenhuoltojärjestelmät eivät ole erillään Euroopan sisämarkkinoista, jotka merkittävästi vaikuttavat terveydenhuoltoon.

Optimization of chromatographic conditions and comparison of extraction efficiencies of four different methods for determination and quantification of pesticide content in bovine milk by UFLC-MS/MS

This paper describes the optimization of a multiresidue chromatographic analysis for the identification and quantification of 20 pesticides in bovine milk, including three carbamates, a carbamate oxime, six organophosphates, two strobilurins, a pyrethroid, an oxazolidinedione, an aryloxyphenoxypropionate acid/ester, a neonicotinoid, a dicarboximide, and three triazoles. The influences of different chromatographic columns and gradients were evaluated. Furthermore, four different extraction methods were evaluated; each utilized both different solvents, including ethyl acetate, methanol, and acetonitrile, and different workup steps. The best results were obtained by a modified QuEChERS method that lacked a workup step, and that included freezing the sample for 2 hours at -20 ºC. The results were satisfactory, yielding coefficients of variation of less than 20%, with the exception of the 50 µg L-1 sample of famoxadone, and recoveries between 70 and 120%, with the exception of acephate and bifenthrin; however, both analytes exhibited coefficients of variation of less than 20%.

Customer-related skills and capabilities in knowledge-intensive business services

The roles of knowledge and customer involvement form distinct features in providing knowledge-intensive business services. The objective of this study was to investigate the customer-related skills and capabilities of knowledge-intensive business services. The research was carried out as case study, involving two polar cases. The other case represented customized services, and the other standardized services. The research method was qualitative, and included focus group workshops, individual interviews and a survey. The capabilities of business services have been mainly studied on organizational level. This study provides valuable insight into the role of individual skills as a part of capabilities of knowledge-intensive business services. According to this study, the most important capabilities are related to acquiring and integrating of knowledge, resource management, managing the customer’s role as a co-producer of the service, and active and effective communication. The study indicates that the level of tacit knowledge is high in the needed individual skills. Based on the study, the needed capabilities and skills are affected by the level of customization of the service, the demand for customer knowledge, the demand for consultation and the stage of the service providing.

The purpose of consumer co-operation: implications for the management and governance of co-operatives

Extant research on consumer co-operation has acknowledged that the corporate purpose of consumer co-operatives deviates significantly from the purpose of investor-owned firms (IOFs – the dominant form in market economies and in theory development in the field of business economics) and also suggested that the management of consumer co-operatives differs from the management of IOFs. Despite this, there is a scarcity of research focusing on the management of consumer co-operatives in general and the ways this different purpose manifests in their management in particular. In other words, research on consumer cooperatives has only started to discover the importance of identifying the premises of these organizations and generating management and organization theories that take them into account. The overall objective of this study is to map out some of the implications that the purpose of consumer co-operation has for the management and governance of consumer co-operatives. To put it more precisely, by combining interview data gathered from Finnish consumer cooperatives (S Group, OP Bank Group and POP Bank) and extant literature, this study aims to generate or elaborate on definitions and outlines of the features that co-operative purpose poses for the strategic management, governance and managerial competence needed for consumer co-operatives. The study consists of two parts. The first part introduces the research topic, methods and publications, as well as discusses the overall outcomes. The second part consists of four publications that address the research questions from different viewpoints. The analyses of this study indicate that due to the purpose of consumer co-operation, the roles of locality and regionality become emphasized in their management. While locality and regionality are potential sources of competitive advantage for consumer co-operatives, geographic boundness sets significant boundary conditions for the strategic management of these organizations. Further, the purpose of consumer co-operation may pose several challenges to governance and set specific competence demands for the managers of these organizations. Associating the observations from various streams of research on management and governance with the purpose of consumer co-operation and examining these issues further, the thesis contributes to elaboration of theory in the field. While the thesis is by no means comprehensive (but instead reflects a co-operative research project in its early stages), it does shed light on some key ideas of management and governance and offers leads to theory and, thereby, will prove useful to elaborators, disseminators and appliers of knowledge on co-operation.

Education export as a form of knowledge transfer : The potential of Finnish education export in Chile

Knowledge transfer is a complex process. Knowledge transfer in the form of exporting education products from one system of education to another is particularly complicated, because each system has been developed in a particular context to meet the requirements seen as relevant at each time. National innovation systems are often seen to form an essential framework within which the development of a country, its economy and level of knowledge are considered and promoted. These systems are orientated towards the future, and as such they also provide a framework for the knowledge transfer related to the development of education. In the best of circumstances they are able to facilitate and boost this transfer both from the viewpoint of the provider and the recipient. The leading thought and the idea of the study is that education export is a form of knowledge transfer, which is illustrated by the existing models included. The purpose of this study is to explore, analyze and describe the factors and phenomena related to education export, and more specifically, those related to the experiences and potential of Finnish education export to Chile. For better understanding, of the multiplicity of the issue involved, the current status of education export between Finland and Chile and he existing efforts within the Finnish innovation network will be outlined as well as new forms of co-operation between Finland and Chile in educational matters explored. Several countries have started to commercialize their education system in order to establish themselves as emerging education exporters. Moreover, the demand for education reform is accurate in many developing countries. This offers a good match between Finland and Chile to be the example countries of the research. The main research findings suggest that there are several business areas in education export. These include degrees in education, training services and education technologies for example The factors that influence education export can be divided into four groups, including academic, cultural, political and economic aspects. Challenges to overcome include the lack of product or services to be sold, lack of market and cultural knowledge of the buyer country, financing and lack of suitable pricing model. National innovation systems could be seen as enabling entities for successful education export. The extensive networks that national innovation systems aim to form, could operate as a basis for joining the forces in selling knowledge as well as receiving knowledge in a constructive way.

Development and evaluation of a loop-mediated isothermal amplification (LAMP) assay for rapid detection of Actinobacillus pleuropneumoniae based the dsbE-like gene

This paper reports on the development and validation of a loop-mediated isothermal amplification assay (LAMP) for the rapid and specific detection of Actinobacillus pleuropneumoniae (A. pleuropneumoniae). A set of six primers were designed derived from the dsbE-like gene of A.pleuropneumoniae and validate the assay using 9 A. pleuropneumoniae reference/field strains, 132 clinical isolates and 9 other pathogens. The results indicated that positive reactions were confirmed for all A. pleuropneumoniae strains and specimens by LAMP at 63ºC for 60 min and no cross-reactivity were observed from other non-A.pleuropneumoniae including Haemophilus parasuis, Escherichia coli, Pasteurella multocida, Bordetella bronchiseptica, Streptococcus suis, Salmonella enterica, Staphylococcus, porcine reproductive and respiratory syndrome virus (PRRSV), and Pseudorabies virus. The detection limit of the conventional PCR was 10² CFU per PCR test tube, while that of the LAMP was 5 copies per tube. Therefore, the sensitivity of LAMP was higher than that of PCR. Moreover, the LAMP assay provided a rapid yet simple test of A. pleuropneumoniae suitable for laboratory diagnosis and pen-side detection due to ease of operation and the requirement of only a regular water bath or heat block for the reaction.

The analysis of knowledge retention mechanisms for leaving experts

The goal of this thesis is studying knowledge retention mechanisms used in cases of single experts’ leaving in the case company, analyzing the reason for the mechanisms choice and successfulness of knowledge retention process depending of that choice. The theoretical part discusses the origins of knowledge retention processes in the theoretical studies, the existing knowledge retention mechanisms and practical issues of their implementation. The empirical part of the study is designed as employees’ interview with later discussion of the findings. The empirical findings indicate the following reasons for knowledge retention mechanisms choice: type of knowledge retained, specialty of leaving experts and time and distance issues of a particular case. The following factors influenced the success of a retention process: choice of knowledge retention mechanisms, usage of combination of mechanisms and creation of knowledge retention plans. The results might be useful for those interested in factors influencing knowledge retention processes in cases of experts’ departure.

Isolation and characterization of the female sex pheromone of the sugar beet cyst nematode, heterodera schachtii, and an analysis of male precopulatory behaviour /

The sugar beet cyst nematode, Heterodera schachtii, is a major agricultural pest. The disruption of the mating behaviour of this plant parasite in the field may provide a means of biological control, and a subsequent increase in crop yield. The H. schachtii female sex pheromone, which attracts homospecific males, was collected in an aqueous medium and isolated using high performance liquid chromatography. Characterization of the male-attractive material revealed that it was heat stable and water soluble. The aqueous medium conditioned by female H. schachtii was found to be biologically active and stimulated male behaviour in a concentration dependent manner. The activity of the crude pheromone was specific to males of H. schachtii and did not attract second stage juveniles. Results indicated that vanillic acid, a putative nematode pheromone, is not an active component of the H. schachtii sex pheromone. Male H. schachtii exhibited stylet thrusting, a poorly understood behaviour of the male, upon exposure to the female sex pheromone. This behaviour appeared to be associated with mate-finding and was used as a novel indicator of biological activity in bioassays. Serotonin, thought to be involved in the neural control of copulatory behaviour in nematodes, stimulated stylet thrusting. However, the relationship between stylet thrusting induced by the sex pheromone and stylet thrusting induced by serotonin is not clear. Extracellular electrical activity was recorded fi-om the anterior region of H. schachtii males during stylet thrusting, and appeared to be associated with this behaviour. The isolation of the female sex pheromone of H. schachtii may, ultimately, lead to the structural identification and synthesis of the active substance for use in a novel biological control strategy.

A multidimensional measurement approach and analysis of children's motivation for reading, attributional style, and reading achievement

The present study investigates the usefulness of a multi-method approach to the measurement of reading motivation and achievement. A sample of 127 elementary and middle-school children aged 10 to 14 responded to measures of motivation, attributions, and achievement both longitudinally and in a challenging reading context. Novel measures of motivation and attributions were constructed, validated, and utilized to examine the relationship between ~ motivation, attributions, and achievement over a one-year period (Study I). The impact of classroom contexts and instructional practices was also explored through a study of the influence of topic interest and challenge on motivation, attributions, and persistence (Study II), as well as through interviews with children regarding motivation and reading in the classroom (Study III). Creation and validation of novel measures of motivation and attributions supported the use of a self-report measure of motivation in situation-specific contexts, and confirmed a three-factor structure of attributions for reading performance in both hypothetical and situation-specific contexts. A one-year follow up study of children's motivation and reading achievement demonstrated declines in all components of motivation beginning at age 10 through 12, and particularly strong decreases in motivation with the transition to middle school. Past perceived competence for reading predicted current achievement after controlling for past achievement, and showed the strongest relationships with reading-related skills in both elementary and middle school. Motivation and attributions were strongly related, and children with higher motivation Fulmer III displayed more adaptive attributions for reading success and failure. In the context of a developmentally inappropriate challenging reading task, children's motivation for reading, especially in terms of perceived competence, was threatened. However, interest in the story buffered some ofthe negative impacts of challenge, sustaining children's motivation, adaptive attributions, and reading persistence. Finally, children's responses during interviews outlined several emotions, perceptions, and aspects of reading tasks and contexts that influence reading motivation and achievement. Findings revealed that children with comparable motivation and achievement profiles respond in a similar way to particular reading situations, such as excessive challenge, but also that motivation is dynamic and individualistic and can change over time and across contexts. Overall, the present study outlines the importance of motivation and adaptive attributions for reading success, and the necessity of integrating various methodologies to study the dynamic construct of achievement motivation.

RNA recurrent motifs : identification and characterization

La détermination de la structure tertiaire du ribosome fut une étape importante dans la compréhension du mécanisme de la synthèse des protéines. Par contre, l’élucidation de la structure du ribosome comme tel ne permet pas une compréhension de sa fonction. Pour mieux comprendre la nature des relations entre la structure et la fonction du ribosome, sa structure doit être étudiée de manière systématique. Au cours des dernières années, nous avons entrepris une démarche systématique afin d’identifier et de caractériser de nouveaux motifs structuraux qui existent dans la structure du ribosome et d’autres molécules contenant de l’ARN. L’analyse de plusieurs exemples d’empaquetage de deux hélices d’ARN dans la structure du ribosome nous a permis d’identifier un nouveau motif structural, nommé « G-ribo ». Dans ce motif, l’interaction d’une guanosine dans une hélice avec le ribose d’un nucléotide d’une autre hélice donne naissance à un réseau d’interactions complexes entre les nucléotides voisins. Le motif G-ribo est retrouvé à 8 endroits dans la structure du ribosome. La structure du G-ribo possède certaines particularités qui lui permettent de favoriser la formation d’un certain type de pseudo-nœuds dans le ribosome. L’analyse systématique de la structure du ribosome et de la ARNase P a permis d’identifier un autre motif structural, nommé « DTJ » ou « Double-Twist Joint motif ». Ce motif est formé de trois courtes hélices qui s’empilent l’une sur l’autre. Dans la zone de contact entre chaque paire d’hélices, deux paires de bases consécutives sont surenroulées par rapport à deux paires de bases consécutives retrouvées dans l’ARN de forme A. Un nucléotide d’une paire de bases est toujours connecté directement à un nucléotide de la paire de bases surenroulée, tandis que les nucléotides opposés sont connectés par un ou plusieurs nucléotides non appariés. L’introduction d’un surenroulement entre deux paires de bases consécutives brise l’empilement entre les nucléotides et déstabilise l’hélice d’ARN. Dans le motif DTJ, les nucléotides non appariés qui lient les deux paires de bases surenroulées interagissent avec une des trois hélices qui forment le motif, offrant ainsi une stratégie élégante de stabilisation de l’arrangement. Pour déterminer les contraintes de séquences imposées sur la structure tertiaire d’un motif récurrent dans le ribosome, nous avons développé une nouvelle approche expérimentale. Nous avons introduit des librairies combinatoires de certains nucléotides retrouvés dans des motifs particuliers du ribosome. Suite à l’analyse des séquences alternatives sélectionnées in vivo pour différents représentants d’un motif, nous avons été en mesure d’identifier les contraintes responsables de l’intégrité d’un motif et celles responsables d’interactions avec les éléments qui forment le contexte structural du motif. Les résultats présentés dans cette thèse élargissent considérablement notre compréhension des principes de formation de la structure d’ARN et apportent une nouvelle façon d’identifier et de caractériser de nouveaux motifs structuraux d’ARN.

Ethical Considerations of Dissemination and Restitution of Findings in Global Health Research

Étude de cas / Case study

Gross Inequality and Inequality of Opportunities in Basic Education: Were they affected by Latin America’s Economic Boom?

In the context of economic growth and recovering socio-economic conditions, many Latin American countries have implemented deep educational reforms since the beginning of the century. This paper aims to analyse whether these changes have promoted equality of educational opportunities in the region. Both the access and knowledge and skills dimensions are evaluated for six important countries, deepening the analysis for Argentina, Brazil and Colombia, in order to better understand the trends observed. Results point to reasonable progress in access, but reflect an unsatisfactory evolution of the level and distribution of knowledge and skills as reflected by PISA test scores.