All living cells are dependent on nucleic acids for their survival. The genetic information stored in DNA is translated into functional proteins via a messenger molecule, the ribonucleic acid (RNA). Since DNA and RNA can be considered as polymers of nucleotides (NTPs), balanced pools of NTPs are crucial to nucleic acid synthesis and repair. The de novo reduction of ribonucleoside diphosphates (NDPs) to deoxyribonucleoside diphosphates (dNDPs), the precursors for DNA synthesis, is catalyzed by the enzyme ribonucleotide reductase (RNR). In cycling cells the dominant form of mammalian RNR consists of two proteins called R1 and R2. A proteasome-mediated degradation completely deprives postmitotic cells of R2 protein. The nonproliferating cells use instead a p53 inducible small RNR subunit, called p53R2 to synthesize dNTPs for mitochondrial DNA replication and DNA repair. To address the ongoing controversy regarding the localization and subsequently function and regulation of RNR subunits, the subcellular localization of all the mammalian RNR subunits during the cell cycle and after DNA damage was followed as a part of this thesis. Irrespective of the employed methodology, only a cytosolic localization could be observed leading to a conclusion that the dNTPs are synthesized in the cytosol and transported into the nucleus or mitochondria for DNA synthesis and repair. Thus, our data do not support the suggestion that nuclear translocation is a new additional mechanism regulating ribonucleotide reduction in mammalian cells. In an attempt to find a cure for African sleeping sickness, a lethal disease caused by a human pathogen, Trypanosoma brucei, nucleotide metabolism of the parasite was studied. The trypanosomes exhibit strikingly low CTP pools compared with mammalian cells and they also lack salvage of cytidine/cytosine making the parasite CTP synthetase a potential target for treatment of the disease. Following expression, purification and kinetic studies of the recombinant T. brucei CTP synthetase it was found that the enzyme has a higher Km value for UTP than the mammalian CTP synthetase. In combination with a lower UTP pool the high Km may account for the low CTP pool in trypanosomes. The activity of the trypanosome CTP synthetase was irreversibly inhibited by the glutamine analog acivicin, a drug extensively tested as an antitumor agent. Daily injections of acivicin to trypanosome-infected mice were sufficient to suppress the parasite infections. The drug was shown to be trypanocidal when added to cultured bloodstream T. brucei for four days at 1 uM concentration. Therefore, acivicin may qualify as a drug with “desirable” properties, i.e. cure within 7 days, according to the current Target Product Profiles of WHO and DNDi. Trypanosomes lack de novo purine biosynthesis and are therefore dependent on exogenous purines such as adenosine that is taken up from the blood by high-affinity transporters. We found that besides the cleavage-dependent pathway, where adenosine is converted to adenine by inosine-adenosine-guanosine-nucleoside hydrolase, T. brucei can also salvage adenosine by adenosine kinase (AK). The efficient adenosine transport combined with a high-affinity AK yields a strong salvage system in T. brucei, but on the other hand makes the parasites highly sensitive to adenosine analogs such as adenine arabinoside (Ara-A). The cleavage-resistant Ara-A was shown to be readily taken up by the parasites and phosphorylated by the TbAK-dependent pathway, inhibiting trypanosome proliferation and survival by incorporation into nucleic acids and by affecting nucleotide levels in the parasite.

La construction à Rome du musée de l'Ara Pacis, conçu par l'architecte américain Richard Meier, suscite depuis plus de dix ans de vives polémiques. Celles-ci dénotent un malaise évident face à l'intégration d'une architecture contemporaine, qualifiée de « générique » par certains, dans le centre historique de la Ville éternelle. L'argument principal des détracteurs du projet repose sur la thèse selon laquelle la complexité des strates historiques et la diversité étonnante des monuments érigés jadis qui composent cette ville-palimpseste se trouveraient soumises à de trop importants changements nuisant à l'intégrité du patrimoine bâti. En effet, dans le cas étudié ici, ils affirment que le musée de l'Ara Pacis constitue encore un autre cas de structure inapte à rendre justice à l'image historique et patrimoniale de Rome. Il en résulte la question qui est au coeur de la problématique abordée dans ce mémoire: le contact d'une architecture contemporaine, qualifiée de « générique » par ceux qui dénoncent le culte des « archi-stars », avec un monument de la Rome antique, peut-il enrichir l'esprit de ce lieu complexe? Par une analyse du pôle de la réception du monument, ce mémoire vise donc à comprendre les impacts, à différentes échelles, de cette construction par rapport à son contexte urbain. En appliquant une approche inspirée du modèle systémique formulé par l'urbaniste Paolo Colarossi et en recourant notamment au concept de « contemporanéité anachronique » développé par l'historien d'art Daniel Arasse ainsi que celui de monument tel que défini par Jean Davallon, entre autres, nous proposons une piste de résolution de l'opposition entre conservation et innovation. Le discours affectif sera donc dépassé par une analyse plus globale. L'approche systémique utilisée transforme ainsi un cas statique et isolé en événement. Bien encadrées, nous soutenons que les nouvelles architectures peuvent actualiser un bien patrimonial tout en faisant surgir de nouvelles valeurs à transmettre dans le futur. Le débat provoqué par la construction du musée de l'Ara Pacis peut aider à approfondir les réflexions menant à un meilleur encadrement pour des projets futurs. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Architecture contemporaine, Paysage urbain historique, Patrimoine, Mise en valeur, Rome, Ara Pacis, Musée de Richard Meier, Approche systémique.

The purpose of this study is to investigate the future of the Swedish newspaper industry. A special interest is taken in local newspapers and its distinguishing features. Our aim is to achieve a better understanding of the development of the Swedish newspaper in light of the looming threath of the death of newspapers. Will print media survive or is the industry forced to a migration to digital platforms? How are newspapers affected by this structural change in an advertisement-driven market? We performed a small case study on Norrtelje Tidning in addition to a historical study of the Swedish newspaper industry. Two-sided market theory was utilized in combination with a model describing actors, activities and resources in a network. This theoretical framework provided an overview of the prevailing market for newspapers, advertisers, and customers which facilitated further analysis of the intricate relations between these groups. The results reveal that the future for print media looks grim, however the uniqueness of content of local newspapers will probably ensure its survival in one form or the other for the foreseeable future.

Orientador: José Jurandir Fagliari / Banca: Raimundo Souza Lopes / Banca: Eliana Reiko Matushima / Banca: Aureo Evangelista Santana / Banca: Karin Werther / Resumo: Os Psittaciformes representam uma das ordens de aves mais comumente criadas como animais de companhia. A identificação de doenças em aves de companhia pode respresentar um desafio diagnóstico. A carência de dados a respeito de perfis normais para psitacídeos, como hemograma e perfil bioquímico sérico, são notórias no país. Pesquisas dessa natureza podem contribuir no diagnóstico e prognóstico de importantes doenças de aves criadas em cativeiro e de vida livre, dentre elas a clamidiose, zoonose de alta prevalência e com diagnóstico definitivo relativamente difícil, devido à complexa fisiopatogenia da infecção causada por Chlamydophila psittaci. Este estudo objetivou a realização do hemograma e o perfil bioquímico, inclusive as concentrações de imunoglobulinas e de proteínas de fase aguda, pela técnica de eletroforese em gel de poliacrilamida contendo dodecil sulfato de sódio - SDS-PAGE, de papagaios-verdadeiro (Amazona aestiva) e araras-canindé (Ara ararauna), de cativeiro, clinicamente saudáveis e o proteinograma em SDS-PAGE de papagaios-verdadeiro e araras-canindé de cativeiro positivos ou negativos para Chlamydophila psittaci. Os valores hematológicos, incluindo o hemograma e bioquímica sérica, foram determinados para ambas as espécies, demonstrando estar entre os intervalos de referência para as mesmas. O proteinograma sérico em SDS-PAGE permitiu a detecção de até 33 proteínas no traçado eletroforético de papagaios-verdadeiro sadios, e até 29 proteínas no traçado eletroforético de araras-canindé sadias. O proteinograma permitiu visualizar diferenças biologicamente importantes nas concentrações das proteínas de fase aguda e imunoglobulinas de papagaios-verdadeiro e araras-canindé positivos e negativos para C. psittaci, principalmente quanto a evidência da proteína de peso molecular 21 kDa, presente somente em papagaios-verdadeiro positivos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Psittaciformes represent one of the most common orders of birds bred as pets. Disease identification in birds can represent a diagnostic challenge. The lack of data about normal ranges for psittacines, like hemogram and serum biochemistry are notorious in this country. Research regarding this subject can contribute to the diagnosis and prognosis of important diseases in captive and free-range birds. One of these diseases is clamidiosis, a zoonotic disease with high prevalence and with definitive diagnosis relatively difficult, because of the complex fisiopatogeny of the infection caused by Chlamydophila psittaci. The objective of this study was to determine the hemogram and serum biochemistry, including serum acute phase proteins and imunoglobulins using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), of clinically healthy, adult, captive blue fronted amazon parrots (Amazona aestiva) and blue and gold macaws (Ara ararauna) and the SDS-PAGE proteinograma of blue fronted amazon parrots and blue and gold macaws testing positive and negative for clamidiosis. The hematological values, including hemogram and serum biochemistry, were determined for both species, showing to be between the normal reference ranges. The SDS-PAGE proteinogram allowed visualization of up to 33 proteins of healthy blue fronted amazon and up to 29 proteins of healthy blue and gold macaws. The proteinogram allowed visualization of important biological differences in the concentrations of acute phase proteins and imunoglobulins of blue fronted amazon parrots and blue and gold macaws, testing positive and negative for clamidiosis. Present only in parrots positive for clamidiosis was the molecular weight 21 kDa protein / Doutor

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-05-30T22:35:17Z No. of bitstreams: 1 MariaRaquelCavalcantiInacio_TESE.pdf: 2176193 bytes, checksum: 1c0288ef05b8770739a332aeef0364e1 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-06-01T21:19:57Z (GMT) No. of bitstreams: 1 MariaRaquelCavalcantiInacio_TESE.pdf: 2176193 bytes, checksum: 1c0288ef05b8770739a332aeef0364e1 (MD5) / Made available in DSpace on 2016-06-01T21:19:57Z (GMT). No. of bitstreams: 1 MariaRaquelCavalcantiInacio_TESE.pdf: 2176193 bytes, checksum: 1c0288ef05b8770739a332aeef0364e1 (MD5) Previous issue date: 2014-12-12 / Neste estudo, foram avaliadas a espectroscopia de reflect?ncia do infravermelho pr?ximo (NIR) e o potencial da calibra??o multivariada como um m?todo r?pido para determinar o teor total de antocianinas em frutos intactos de a?a? e palmiteiro ju?ara. Diversas t?cnicas de calibra??o multivariadas, incluindo regress?o por m?nimos quadrados parciais (PLS), M?nimos Quadrados Parciais por Intervalo (iPLS), algoritmo gen?tico (AG), algoritmo das proje??es sucessivas (APS),foram comparadas e validadas pelo c?lculo das figuras de m?rito. Resultados adequados foram obtidos com o modelo PLS (4 vari?veis latentes e suaviza??o em janela com 5 pontos) com limite de detec??o de 6,2 g.kg-1, limite de quantifica??o de 20,7 g.kg-1, precis?o estimada como raiz quadrada da m?dia do erro da previs?o (RMSEP) de 4,8 g.kg-1, seletividade de 0,79 g.kg-1, sensibilidade de 5,04 x 10-3 g kg-1, precis?o de 27,8 g.kg-1 e a raz?o sinal-ru?do foi de 1,04 x 10-3 g.kg-1. Estes resultados sugerem que a espectroscopia NIR e a calibra??o multivariada podem ser efetivamente usadas para determinar o teor de antocianinas em frutos intactos de a?a? e palmiteiro ju?ara. / In this study was evaluated near-infrared reflectance spectroscopy (NIR), and multivariate calibration potential as a rapid method to determinate anthocyanin content in intact fruit (a?a? and palmitero-ju?ara). It?s important to develop new methods to determinate quality parameters in foods, mostly the use of quick techniques, non-invasive and which have reliable methods. The NIR spectroscopy fills these requirements and these have shown as an alternative to conventional quality control analysis in several foods, including, fruit. Currently, analytical methods have been reported to determinate anthocyanin in fruits. However, the NIR spectroscopy is cited rarely to determinate anthocyanin content in a?a? and palmitero-ju?ara. This study could contribute to research that already have performed. Several multivariate calibration techniques, including partial least squares (PLS), interval partial least squares (iPLS), genetic algorithm (AG), successive projections algorithm (SPA), were compared and validated by establishing figures of merit. In this job, 139 fruits were used, 69 were acai and 70 were palmiteiro ju?ara. The potential anthocyanin sources has been quantified using differential pH method, as a reference method. Soon after, the near-infrared diffuse reflectance spectra have been measured, and finally the chemometrics models have been built. Suitable results were obtained with the PLS model (four latent variables and 5- point smoothing) with a detection limit of 6.2 g kg-1, limit of quantification of 20.7 g kg-1, accuracy estimated as root mean square error of prediction of 4.8 g kg-1, mean selectivity of 0.79 g kg-1, sensitivity of 5.04 x10-3 g kg-1, precision of 27,8 g kg-1, and signal-to-noise ratio of 1.04 x10-3 g kg-1. These results suggest NIR spectroscopy and multivariate calibration can effectively be used to determine anthocyanin content in intact a?a? and palmitero-ju?ara fruit.

Philosophiae Doctor - PhD / This dissertation documents the attempt to address one of the major problems in nursing education i.e. the existing gap between the educational philosophy of nursing and nursing education practices, by means of an action research project during the period 1991-1996. The research in this dissertation is recorded in three phases. Phase One elaborates on the biographical and professional background of the researcher and the reasons why action research was selected for the purpose of this particular project Since action research provides opportunities for teachers to change and transform their own teaching practices, it was obviously the best choice for the research. The emphasis was on collaboration and participation and the researcher was morally bound to consider and observe all internal and external factors which influence and limit her own teaching practice, in order to initiate change and transformation in teaching. In order to define and contextualize the problem and to describe the situation in which this particular problem has been identified, the role of the statutory body, the South African Nursing Council which governs the profession and basic professional nursing education were explored. The problem is formulated as the existing gap between the educational philosophy on which existing nursing and nursing education practices are theoretically grounded and the way in which both nursing and nursing education practices appear in reality. Phase One also deals with the historical and philosophical foundations and development of nursing and nursing education. In an attempt to describe the researchers's teaching practice appropriately, as a social practice, it was essential to consider not only the professional and social boundaries of nursing education, but also the current situation regarding national education, the existing health system and all factors related to education and health. The dissertation then draws the attention to the essential features and historical context of a progressive and critical pedagogy, as a foundation for action research. In this regard it was especially the contributions of Dewey, Habermas, Freire, Giroux and McLaren, which guided the research to approach nursing education from a critical perspective. Phase Two deals with the research methodology. For this particular research project John Elliotts's Action Research Framework for Self-Evaluation in Schools was used. Within this framework of Elliott the dissertation then describes the research methodology of this particular project: Ideal and Reality in Nursing Education and Nursing Practices in South Africa: An Action Research Approach. The rationale and the development of the project is first described, whereafter action research is discussed as a process which enables nursing .practitioners and tutors to become empowered and to initiate change and establish transformation within their own practices. A major part of the dissertation is dedicated to the project in action with two groups of participants during two action research cycles. Finally Phase Three of this dissertation draws the attention to the conclusions based on the outcomes of the project. with the emphasis on the urgent need for change and transformation within the nursing profession in order to lessen the extensive gap between nursing theory and nursing practices. The existing gap between the philosophy on which nursing practices are based and how existing nursing practices appear in reality, seems to be the major cause of the prevailing discontent in the nursing profession.

This research is a qualitative case study at the industrial business-to-business startup Nytt Tech aiming to understand how startups work with networkbased relationship marketing in the early phase and how they gain access to the business network and benefit from creating relationships. The following research question is presented: How can a business-to-business startup gain access to and benefit from the business network to create relationships? The study is limited to Nytt Tech and the circumstances that prevail for them. As a basis, unstructured and semi-structured interviews have been held with the employees and key customers to understand how success has arisen so far and then examine how it can be further developed. The data has been processed and analyzed using the ARA-model as the theoretical framework. The study finds multiple drivers which will help Nytt Tech for continued growth. In terms of Actors, the close collaboration with their customers contributes to both knowledge and feedback. Simultaneously, it generates revenue and spreads the word, which can cause more paying customers. In terms of Resources, the close collaboration between university and industry is an essential resource in several areas; recruitment of talented and ambitious students, product development deeply rooted in research, and direct opportunity to apply the theory in practice. Finally, in terms of Activities, direct contact reduces the risk of creating a distance between the company's offer and the customer's actual needs, leading to increased success. To conclude, companies can gain access to and benefit from the business network by activating direct and indirect business relationships and working closely together over time. A startup company may not have established business relationships, but its people do. Each person has a network that is combined uniquely. Therefore, recommendations are given that the case company should continue to work closely and use their own and partners' business networks to access new potential customers.

No description available.

The vestibuloocular reflex can be manually elicited by tilting or rotating the head. Manual techniques serve their purpose well and is the golden standard in the clinical work, but they lack control of velocity and movement pattern. However, motion simulation platforms enable automatic control of both velocity and movement pattern. One motion simulation platform, named BIRGIT, has been built at the Department of Clinical Neurosciences at Karolinska Institutet but has not yet been in service and require a performance evaluation. The objectives with this thesis is to evaluate the accuracy and precision of BIRGIT and evaluate how bodyweight and movement direction impact the performance. The thesis also evaluate whether it is possible to stabilize the head of the patient during the acceleration phase. Repeated measurements of acceleration with different loads, desired ac- celeration, direction and motion type (rotational and translational), are per- formed. Dummies are used to simulate bodyweight in the performance study and real persons are used in the head stabilization study. Analysis of variance (ANOVA) is the main statistical tool. The results suggest that the platform does not perform equally at dif- ferent load or directions and that there is a bias between desired and true acceleration. The main problems are an inclination of the rails, upon which the chair is mounted, that causes differences between directions and an un- desirable performance characteristic for rotational motions. The stabilization study suggest that the head can be stabilized. / Den vestibulo-okul ̈ara reflexen kan framkallas genom att manuellt rotera eller rycka p ̊a huvudet. Att manuellt framkalla reflexen fungerar i de flesta sam- manhang va ̈l och a ̈r standard i m ̊anga underso ̈kningar. Dock g ̊ar det inte att till fullo kontrollera vare sig hastighet eller ro ̈relsebana perfekt. Emellertid g ̊ar detta att kontrollera genom att anva ̈nda sig av en s ̊a kallad ro ̈relsesimu- leringsplatform. En s ̊adan platform, d ̈opt till BIRGIT, har byggts vid Institutionen f ̈or kliniska neurovetenskaper vid Karolinska Institutet. Denna har ej bo ̈rjat anva ̈ndas ̈annu d ̊a dess prestanda fo ̈rst beho ̈ver utv ̈arderas. Syftet med denna uppsats ̈ar att utva ̈rdera precision och noggrannhet hos BIRGIT. Dessutom, att utv ̈ardera hur kroppsvikt och ro ̈relseriktning inverkar p ̊a prestandan. I arbetet ing ̊ar ̈aven att testa om det a ̈r m ̈ojligt att stabilisera huvudet under accelerationsfasen. Repeterade ma ̈tningar av sann acceleration med olika last, riktning, bo ̈rac- celeration och r ̈orelsetyp (rotation eller sidledes) genomfo ̈rdes. Testdockor anva ̈ndes fo ̈r att simulera lasten i prestandatesterna och riktiga testpersoner anva ̈ndes i huvudstabiliseringsdelen. Variansanalys (ANOVA) var det hu- vudsakliga statistiska verktyget. Resultatet antyder att last och ro ̈relseriktning inverkar p ̊a acceleratio- nen och prestandan och att den sanna accelerationen alltigenom a ̈r la ̈gre a ̈n bo ̈raccelerationen. Det finns tv ̊a sto ̈rre problem hos plattformen, det fo ̈rsta a ̈r att uppha ̈ngningen till stolen lutar och detta resulterar i en skillnad mellan riktningarna (det g ̊ar fortare nedf ̈ors). Det andra problemet a ̈r ett cykliskt uppfo ̈rande na ̈r flera rotationsr ̈orelser skall fo ̈lja p ̊a varandra. Stabiliseringsstudien visade att det g ̊ar att stabilisera huvudet.

Social media (SM) is an innovative strategy used to develop new forms of communication channels and platforms. This has led to a positive transformation in the marketing strategy for both small-and-medium enterprises (SMEs) and large enterprises. There has been a lot of research conducted on the utilization of SM by Business-to-Consumer (B2C) marketing. However, the use of SM in Business-to-Business (B2B) marketing has not been explored as much in comparison to B2C marketing. The aim of this study is to understand the role of SM channels in B2B service-based SMEs, while also analyzing the challenges and opportunities incorporated by the integration of the SM platforms and the impact it has on B2B relationships. Our research builds on the Industrial Marketing and Purchasing (IMP) related “Activities-Resources-Actors (ARA) Model” and the interconnection between the three layers to understand and analyze the utilization of SM.  This study takes a qualitative case study approach to answer the research question formulated in this study by conducting semi-structured interviews. The interviewees included five respondents: two from the focal company and three from their existing business networks. From the findings, three themes were formulated to understand and analyze the data collected: Adoption decision of SM channels in the case SME and the network firm, Collaboration process with the business customers, and Content co-creation. Based on the findings we conclude that SM is an emerging tool for SMEs to incorporate it in their marketing strategy. It can help the firm to improve the bonds between the actors within the organization as well as with their customers and networks. However, the successful utilization of SM in SMEs depends on the commitment of SMEs to incorporate SM tools effectively in their operations. This can be achieved by the “Hybrid approach” by integrating SM communication with the conventional modes of communication for B2B marketing.