443 resultados para Mikkonen, Pirjo
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PURPOSE Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle(14),Lys(40)(Ahx-NODAGA-(64)Cu)NH2]-exendin-4 ([(64)Cu]NODAGA-exendin-4) and [Nle(14),Lys(40)(Ahx-NODAGA-(68)Ga)NH2]-exendin-4 ([(68)Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents. PROCEDURES The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated. RESULTS We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [(64)Cu]NODAGA-exendin-4 and [(68)Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively. CONCLUSION [(64)Cu]NODAGA-exendin-4 might be more effective for labelling islets than [(68)Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [(68)Ga]NODAGA-exendin-4 compared to [(64)Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [(64)Cu]NODAGA-exendin-4 as a clinical tracer.
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In this work, electrophoretic preconcentration of protein and peptide samples in microchannels was studied theoretically using the 1D dynamic simulator GENTRANS, and experimentally combined with MS. In all configurations studied, the sample was uniformly distributed throughout the channel before power application, and driving electrodes were used as microchannel ends. In the first part, previously obtained experimental results from carrier-free systems are compared to simulation results, and the effects of atmospheric carbon dioxide and impurities in the sample solution are examined. Simulation provided insight into the dynamics of the transport of all components under the applied electric field and revealed the formation of a pure water zone in the channel center. In the second part, the use of an IEF procedure with simple well defined amphoteric carrier components, i.e. amino acids, for concentration and fractionation of peptides was investigated. By performing simulations a qualitative description of the analyte behavior in this system was obtained. Neurotensin and [Glu1]-Fibrinopeptide B were separated by IEF in microchannels featuring a liquid lid for simple sample handling and placement of the driving electrodes. Component distributions in the channel were detected using MALDI- and nano-ESI-MS and data were in agreement with those obtained by simulation. Dynamic simulations are demonstrated to represent an effective tool to investigate the electrophoretic behavior of all components in the microchannel.
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The potential shown by Lean in different domains has aroused interest in the software industry. However, it remains unclear how Lean can be effectively applied in a domain such as software development that is fundamentally different from manufacturing. This study explores how Lean principles are implemented in software development companies and the challenges that arise when applying Lean Software Development. For that, a case study was conducted at Ericsson R&D Finland, which successfully adopted Scrum in 2009 and subsequently started a comprehensible transition to Lean in 2010. Focus groups were conducted with company representatives to help devise a questionnaire supporting the creation of a Lean mindset in the company (Team Amplifier). Afterwards, the questionnaire was used in 16 teams based in Finland, Hungary and China to evaluate the status of the transformation. By using Lean thinking, Ericsson R&D Finland has made important improvements to the quality of its products, customer satisfaction and transparency within the organization. Moreover, build times have been reduced over ten times and the number of commits per day has increased roughly five times.The study makes two main contributions to research. First, the main factors that have enabled Ericsson R&D?s achievements are analysed. Elements such as ?network of product owners?, ?continuous integration?, ?work in progress limits? and ?communities of practice? have been identified as being of fundamental importance. Second, three categories of challenges in using Lean Software Development were identified: ?achieving flow?, ?transparency? and ?creating a learning culture?
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Acknowledgements This paper belongs to the studies carried out by Kuopio Birth Cohort consortium (www.KuBiCo.fi). We thank Ms Pirjo Hänninen for expert laboratory assistance at University of Eastern Finland, Ms Margaret Fraser, Dr Panagiotis Filis and the Proteomics Core Facility at the University of Aberdeen for their expert assistance. We also thank the staff of the Department of Obstetrics and Gynaecology in Kuopio University Hospital for skilful collection of these specimens. This work was supported by the Academy of Finland [122859/2007], the Helena Vuorenmies Foundation, the Emil Aaltonen Foundation, the University of Eastern Finland Doctoral Programme in Drug Research and the Medical Research Council, UK [MR/L010011/1]. The funders played no roles in study design, data collection, data analysis, manuscript preparation and/or publication decisions.
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Este trabajo analiza los resultados de una investigación sobre hábitos lectores del alumnado asturiano de 6º de Educación Primaria en su tiempo libre. El estudio utiliza una muestra de 324 escolares de centros públicos urbanos, con edades comprendidas entre los 11 y 12 años, para analizar datos relativos a la actitud hacia la lectura, la importancia de ésta entre las actividades de ocio y la frecuencia lectora.Más de la mitad de los escolares manifiesta una actitud bastante favorable hacia la lectura, y ésta es una de sus actividades de ocio habituales, aunque dedican más tiempo a ver televisión, practicar deportes, usar el ordenador y escuchar música. La mayoría son lectores frecuentes, aunque los no lectores y lectores ocasionales ascienden hasta un 12,96%. Los escolares encuestados leen principalmente libros, seguidos de revistas y cómics, mientras que poco más de un tercio dice leer periódicos frecuentemente.Esta investigación revela también algunas variaciones en actitud hacia la lectura y frecuencia lectora según el centro educativo de procedencia que se pueden relacionar con variables de tipo socio-económico. Además, se observan diferencias entre niños y niñas, pues éstas superan a sus compañeros varones en interés y frecuencia lectora, además de manifestar también divergencias en las preferencias de materiales de lectura.
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Valtiontukisäännökset ovat olennainen osa EU-vero-oikeutta sekä EU-kilpailuoikeutta. Näiden arvioinnissa on vastakkain toimivat sisämarkkinat EU:ssa ja sisämarkkinoilla toimivien yritysten tarve saada taloudellista tukea. Valtiontukisäännösten soveltaminen välittömän verotuksen muodossa annettuihin verotukiin on erityisen hankalaa, koska välitöntä verotusta ei unionintasolla ole harmonisoitu. Tässä tutkielmassa tutkitaan välittömän verotuksen muodossa annettujen valtiontukien soveltuvuutta EU:n sisämarkkinoille ja erityisesti verotuen valikoivuuden arviointia. Kielletyn valtiontuen kriteereistä valikoivuuden tunnistaminen on erityisen hankalaa, koska tämä edellyttää jäsenvaltioiden verojärjestelmien perus- tai pääperiaatteiden tuntemusta. Valtiontukisäännösten soveltuvuutta verotukiin voidaan tästä syystä kyseenalaistaa. Voimassa olevan oikeustilan mukaan EU:n toimielimet arvioivat kansallista verotoimenpidettä ja sen myötä koko kansallista verojärjestelmää. Valtiontukisäännösten suhde muihin säännöksin mm. perusvapauksiin on myös ongelmallinen, osittain päällekkäisen soveltamisalan vuoksi. EU:n tasolla tahtotila vaikuttaisi olevan valtiontukisäännösten soveltaminen verotukiin myös jatkossa. Tämä ei kuitenkaan välttämättä ole vaihtoehdoista tarkoituksenmukaisin. Tämä tahtotila yhdessä jäsenvaltioilla olevalla, ainakin muodollisella suvereniteetilla välittömän verotuksen saralla, on tulevaisuuden oikeustilaa ajatellen mahdoton yhtälö.