Lipid rafts act as specialised domains for tetanus toxin binding and internalisation in neurons

Tetanus (TeNT) is a zinc protease that blocks neurotransmission by cleaving the synaptic protein vesicle-associated membrane protein/synaptobrevin. Although its intracellular catalytic activity is well established, the mechanism by which this neurotoxin interacts with the neuronal surface is not known. In this study, we characterize p15s, the first plasma membrane TeNT binding proteins and we show that they are glycosylphosphatidylinositol-anchored glycoproteins in nerve growth factor (NGF)-differentiated PC12 cells, spinal cord cells, and purified motor neurons. We identify p15 as neuronal Thy-1 in NGF-differentiated PC12 cells. Fluorescence lifetime imaging microscopy measurements confirm the close association of the binding domain of TeNT and Thy-1 at the plasma membrane. We find that TeNT is recruited to detergent-insoluble lipid microdomains on the surface of neuronal cells. Finally, we show that cholesterol depletion affects a raft subpool and blocks the internalization and intracellular activity of the toxin. Our results indicate that TeNT interacts with target cells by binding to lipid rafts and that cholesterol is required for TeNT internalization and/or trafficking in neurons.

Abolishing mammography screening programs?

Biller-Andorno and Jüni (2014), in a widely debated commentary published in the May 22 issue of the New England Journal of Medicine, accept the concept that mammography every 2 years from age 50 can decrease breast cancer mortality by 20%, that is, from five to four deaths per 1000 women over a 10-year period. Both the absolute and the relative risk of breast cancer death may vary depending on the baseline mortality rates in various populations and on the impact of screening mammography in reducing breast cancer mortality, which may well vary around the 20% estimate adopted. We accept, therefore, that there are still uncertainties in the absolute and relative impact of mammography screening on breast cancer mortality, given the different study schemes and mammography intervals, the differences in populations, and the continuous improvements in technology (Warner, 2011; Independent UK Panel on Breast Cancer Screening, 2012). We also agree on the observation that mammography has an appreciable impact on breast cancer mortality (Bosetti et al., 2012), but clearly a much smaller one on total mortality.

Tuning Performance of Multi-threaded programs

Diplomityö tarkastelee säikeistettyä ohjelmointia rinnakkaisohjelmoinnin ylemmällä hierarkiatasolla tarkastellen erityisesti hypersäikeistysteknologiaa. Työssä tarkastellaan hypersäikeistyksen hyviä ja huonoja puolia sekä sen vaikutuksia rinnakkaisalgoritmeihin. Työn tavoitteena oli ymmärtää Intel Pentium 4 prosessorin hypersäikeistyksen toteutus ja mahdollistaa sen hyödyntäminen, missä se tuo suorituskyvyllistä etua. Työssä kerättiin ja analysoitiin suorituskykytietoa ajamalla suuri joukko suorituskykytestejä eri olosuhteissa (muistin käsittely, kääntäjän asetukset, ympäristömuuttujat...). Työssä tarkasteltiin kahdentyyppisiä algoritmeja: matriisioperaatioita ja lajittelua. Näissä sovelluksissa on säännöllinen muistinkäyttökuvio, mikä on kaksiteräinen miekka. Se on etu aritmeettis-loogisissa prosessoinnissa, mutta toisaalta huonontaa muistin suorituskykyä. Syynä siihen on nykyaikaisten prosessorien erittäin hyvä raaka suorituskyky säännöllistä dataa käsiteltäessä, mutta muistiarkkitehtuuria rajoittaa välimuistien koko ja useat puskurit. Kun ongelman koko ylittää tietyn rajan, todellinen suorituskyky voi pudota murto-osaan huippusuorituskyvystä.

The Swiss reform of the allocation of tasks : The conventions-programs as a new partnership model for vertical cooperation ?

This research examines the impacts of the Swiss reform of the allocation of tasks which was accepted in 2004 and implemented in 2008 to "re-assign" the responsibilities between the federal government and the cantons. The public tasks were redistributed, according to the leading and fundamental principle of subsidiarity. Seven tasks came under exclusive federal responsibility; ten came under the control of the cantons; and twenty-two "common tasks" were allocated to both the Confederation and the cantons. For these common tasks it wasn't possible to separate the management and the implementation. In order to deal with nineteen of them, the reform introduced the conventions-programs (CPs), which are public law contracts signed by the Confederation with each canton. These CPs are generally valid for periods of four years (2008-11, 2012-15 and 2016-19, respectively). The third period is currently being prepared. By using the principal-agent theory I examine how contracts can improve political relations between a principal (Confederation) and an agent (canton). I also provide a first qualitative analysis by examining the impacts of these contracts on the vertical cooperation and on the implication of different actors by focusing my study on five CPs - protection of cultural heritage and conservation of historic monuments, encouragement of the integration of foreigners, economic development, protection against noise and protection of the nature and landscape - applied in five cantons, which represents twenty-five cases studies.

Evaluation of Teacher Education Programs by Students and Graduates

The purpose of this research was to do a repeated cross-sectional research on class teachers who study in the 4th year and also graduated at the Faculty of Education, University of Turku between the years of 2000 through 2004. Specifically, seven research questions were addressed to target the main purpose of the study: How do class teacher education masters’ degree senior students and graduates rate “importance; effectiveness; and quality” of training they have received at the Faculty of Education? Are there significant differences between overall ratings of importance; effectiveness and quality of training by year of graduation, sex, and age (for graduates) and sex and age (for senior students)? Is there significant relationship between respondents’ overall ratings of importance; effectiveness and their overall ratings of the quality of training and preparation they have received? Are there significant differences between graduates and senior students about importance, effectiveness, and quality of teacher education programs? And what do teachers’ [Graduates] believe about how increasing work experience has changed their opinions of their preservice training? Moreover the following concepts related to the instructional activities were studied: critical thinking skills, communication skills, attention to ethics, curriculum and instruction (planning), role of teacher and teaching knowledge, assessment skills, attention to continuous professional development, subject matters knowledge, knowledge of learning environment, and using educational technology. Researcher also tried to find influence of some moderator variables e.g. year of graduation, sex, and age on the dependent and independent variables. This study consisted of two questionnaires (a structured likert-scale and an open ended questionnaire). The population in study 1 was all senior students and 2000-2004 class teacher education masters’ degree from the departments of Teacher Education Faculty of Education at University of Turku. Of the 1020 students and graduates the researcher was able to find current addresses of 675 of the subjects and of the 675 graduates contacted, 439 or 66.2 percent responded to the survey. The population in study 2 was all class teachers who graduated from Turku University and now work in the few basic schools (59 Schools) in South- West Finland. 257 teachers answered to the open ended web-based questions. SPSS was used to produce standard deviations; Analysis of Variance; Pearson Product Moment Correlation (r); T-test; ANOVA, Bonferroni post-hoc test; and Polynomial Contrast tests meant to analyze linear trend. An alpha level of .05 was used to determine statistical significance. The results of the study showed that: A majority of the respondents (graduates and students) rated the overall importance, effectiveness and quality of the teacher education programs as important, effective and good. Generally speaking there were only a few significant differences between the cohorts and groups related to the background variables (gender, age). The different cohorts were rating the quality of the programs very similarly but some differences between the cohorts were found in the importance and effectiveness ratings. Graduates of 2001 and 2002 rated the importance of the program significantly higher than 2000 graduates. The effectiveness of the programs was rated significantly higher by 2001 and 2003 graduates than other groups. In spite of these individual differences between cohorts there were no linear trends among the year cohorts in any measure. In respondents’ ratings of the effectiveness of teacher education programs there was significant difference between males and females; females rated it higher than males. There were no significant differences between males’ and females’ ratings of the importance and quality of programs. In the ratings there was only one difference between age groups. Older graduates (35 years or older) rated the importance of the teacher training significantly higher that 25-35 years old graduates. In graduates’ ratings there were positive but relatively low correlations between all variables related to importance, effectiveness and quality of Teacher Education Programs. Generally speaking students’ ratings about importance, effectiveness and quality of teacher education program were very positive. There was only one significant difference related to the background variables. Females rated higher the effectiveness of the program. The comparison of students’ and graduates’ perception about importance, effectiveness, and quality of teacher education programs showed that there were no significant differences between graduates and students in the overall ratings. However there were differences in some individual variables. Students rated higher in importance of “Continuous Professional Development”, effectiveness of “Critical Thinking Skills” and “Using Educational Technology” and quality of “Advice received from the advisor”. Graduates rated higher in importance of “Knowledge of Learning Environment” and effectiveness of “Continuous Professional Development”. According to the qualitative data of study 2 some graduates expressed that their perceptions have not changed about the importance, effectiveness, and quality of training that they received during their study time. They pointed out that teacher education programs have provided them the basic theoretical/formal knowledge and some training of practical routines. However, a majority of the teachers seems to have somewhat critical opinions about the teacher education. These teachers were not satisfied with teacher education programs because they argued that the programs failed to meet their practical demands in different everyday situations of the classroom e.g. in coping with students’ learning difficulties, multiprofessional communication with parents and other professional groups (psychologists and social workers), and classroom management problems. Participants also emphasized more practice oriented knowledge of subject matter, evaluation methods and teachers’ rights and responsibilities. Therefore, they (54.1% of participants) suggested that teacher education departments should provide more practice-based courses and programs as well as closer collaboration between regular schools and teacher education departments in order to fill gap between theory and practice.

Facilitating coordination improvement efforts in cross-functional process development programs

Business process improvement is a common approach in increasing the effectiveness of an organization. It can be seen as an effort to increase coordination between units. Process improvement has proved to be challenging, and most management consultation firms facilitate organizations in this kind of initiatives. Cross-functional improvement is one of the main areas for internal consultants as well. However, the needs, challenges and means of cross-functional help have been rarely discussed in the literature. The objective of this thesis is on one hand to present a conceptual and descriptive framework to help understand the challenges of facilitating coordination improvement efforts in cross-functional improvement programs, and on the other hand to develop and test feasible solutions for some facilitation situations. The research questions are: 1. Why and in what kind of situations do organizations need help in developing coordination in cross-functional processes? 2. How can a facilitator help organizations in improving coordination to develop cross-functional processes? The study consists of two parts. The first part is an overview of the dissertation, and the second part comprises six research publications. The theoretical background for the study are the differentiation causing challenges in cross-functional settings, the coordination needed to improve processes, change management principles, methods and tools, and consultation practises. Three of the publications introduce tools for helping in developing prerequisites, planning responsibilities and supporting learning during the cross-functional program. The three other papers present frameworks to help understand and analyse the improvement situation. The main methodological approaches used in this study are design science research, action research and case research. The research data has been collected from ten cases representing different kinds of organizations, processes and developing situations. The data has been collected mainly by observation, semi-structured interviews and questionnaires. The research contributes to the rare literature combining coordination theories and process improvement practises. It also provides additional understanding of a holistic point of view in process improvement situations. The most important contribution is the addition to the theories of facilitating change in process improvement situations. From the managerial point of view, this study gives advice to managers and consultants in planning and executing cross-functional programs. The main factors increasing the need for facilitation are the challenges for differentiation, challenges of organizational change in general, and the novelty of initiatives and improvement practices concerning process development. Organizations need help in creating the prerequisites to change, in planning initiatives, easing conflict management and collaboration between groups, as well as supporting the learning of cross-functional improvement. The main challenges of facilitation are combining the different roles as a consultant, maintaining the ownership for the improvement project with the client, and supporting learning in the client organization.

Optimización y aproximación al problema de la regresión simbólica a través de Straight Line Programs (SLP's) y algoritmos genéticos : Entrenamiento genético de SLP's

El problema de la regresión simbólica consiste en el aprendizaje, a partir de un conjunto muestra de datos obtenidos experimentalmente, de una función desconocida. Los métodos evolutivos han demostrado su eficiencia en la resolución de instancias de dicho problema. En este proyecto se propone una nueva estrategia evolutiva, a través de algoritmos genéticos, basada en una nueva estructura de datos denominada Straight Line Program (SLP) y que representa en este caso expresiones simbólicas. A partir de un SLP universal, que depende de una serie de parámetros cuya especialización proporciona SLP's concretos del espacio de búsqueda, la estrategia trata de encontrar los parámetros óptimos para que el SLP universal represente la función que mejor se aproxime al conjunto de puntos muestra. De manera conceptual, este proyecto consiste en un entrenamiento genético del SLP universal, utilizando los puntos muestra como conjunto de entrenamiento, para resolver el problema de la regresión simbólica.

Characterisation of pigment particles by scanning electron microscope and image analysis programs

Coating and filler pigments have strong influence to the properties of the paper. Filler content can be even over 30 % and pigment content in coating is about 85-95 weight percent. The physical and chemical properties of the pigments are different and the knowledge of these properties is important for optimising of optical and printing properties of the paper. The size and shape of pigment particles can be measured by different analysers which can be based on sedimentation, laser diffraction, changes in electric field etc. In this master's thesis was researched particle properties especially by scanning electron microscope (SEM) and image analysis programs. Research included nine pigments with different particle size and shape. Pigments were analysed by two image analysis programs (INCA Feature and Poikki), Coulter LS230 (laser diffraction) and SediGraph 5100 (sedimentation). The results were compared to perceive the effect of particle shape to the performance of the analysers. Only image analysis programs gave parameters of the particle shape. One part of research was also the sample preparation for SEM. Individual particles should be separated and distinct in ideal sample. Analysing methods gave different results but results from image analysis programs corresponded even to sedimentation or to laser diffraction depending on the particle shape. Detailed analysis of the particle shape required high magnification in SEM, but measured parameters described very well the shape of the particles. Large particles (ecd~1 µm) could be used also in 3D-modelling which enabled the measurement of the thickness of the particles. Scanning electron microscope and image analysis programs were effective and multifunctional tools for particle analyses. Development and experience will devise the usability of analysing method in routine use.

The Pursued Benefits of Customer Loyalty Programs

Customer loyalty programs have increased in recent decades and customers are members in several loyalty programs. Loyalty programs are seen as a tool of exploiting customer relationship management with the aim of long-term, profitable customer relationships. Companies have created such a market where customers are rewarded automatically, even if they are disloyal. In addition, companies are struggling as they try to motivate customers to purchase more and make more frequent visits.

Experimental alternatives for evaluation of progenies and clones in eucalyptus breeding programs

The feasibility of using augmented block designs and spatial analysis methods for early stage selection in eucalyptus breeding programs was tested. A total of 113 half-sib progenies of Eucalyptus urophylla and eight clones were evaluated in an 11 x 11 triple lattice experiment at two locations: Posto da Mata (Bahia, Brazil) and São Mateus (Minas Gerais, Brazil). Four checks were randomly allocated within each block. Plots consisted of 15 m long rows containing 6 plants spaced 3 m apart. The girth at breast height (cm/plant) was evaluated at 19 and 26 months of age. Variance analyses were performed according to the following methods: lattice design, randomized complete block design, augmented block design, Papadakis method, moving means method, and check plots. Comparisons among different methods were based on the magnitude of experimental errors and precision of the estimates of genetic and phenotypic parameters. General results indicated that augmented block design is useful to evaluate progenies and clones in early selection in eucalyptus breeding programs using moderate and low selection intensities. However, this design is not suitable for estimating genetic and phenotypic parameters due to its low precision. Check plots, nearest neighbour, Papadakis (1937), and moving means methods were efficient in removing the heterogeneity within blocks. These efficiencies were compared to that in lattice analysis for estimation of genetic and phenotypic parameters.

Evolution of Bordetella pertussis post vaccination

Evolution of Bordetella pertussis post vaccination Whooping cough or pertussis is caused by the gram-negative bacterium Bordetella pertussis. It is a highly contiguous disease in the human respiratory tract. Characteristic of pertussis is a paroxysmal cough with whooping sound during gasps of breath after coughing episodes. It is potentially fatal to unvaccinated infants. The best approach to fight pertussis is to vaccinate. Vaccinations against pertussis have been available from the 1940s. Traditionally vaccines were whole-cell pertussis (wP) preparations as part of the combined diphtheria-tetanus-pertussis (DTP) vaccines. More recently acellular pertussis (aP) vaccines have replaced the wP vaccines in many countries. The aP vaccines are less reactogenic and can also be administered to school children and adults. There are several publications reporting variation in the i>B. pertussis virulence factors that are also aP vaccine antigens. This has occurred in the genes coding for pertussis toxin and pertactin about 15 to 30 years after the introduction of pertussis vaccines to immunisation programs. Resurgence of pertussis has also been reported in many countries with high vaccination coverage. In this study the evolution of B. pertussis was investigated in Finland, the United Kingdom, Poland, Serbia, China, Senegal and Kenya. These represent countries with a long history of high vaccination coverage with stable vaccines or changes in the vaccine formulation; countries which established high vaccination coverage late; and countries where vaccinations against pertussis were started late. With bacterial cytotoxicity and cytokine measurements, comparative genomic hybridisation, pulsed-field gel electrophoresis (PFGE), genotyping and serotyping it was found that changes in the vaccine composition can postpone the emergence of antigenic variants. It seems that the change in PFGE profiles and the loss of genetic material in the genome of B. pertussis are similar in most countries and the vaccine-induced immunity is selecting non-vaccine type strains. However, the differences in the formulation of the vaccines, the vaccination programs and in the coverage of pertussis vaccination have affected the speed and timing of these changes.