Lack of original antigenic sin in recall CD8(+) T cell responses.

In the real world, mice and men are not immunologically naive, having been exposed to numerous antigenic challenges. Prior infections sometimes negatively impact the response to a subsequent infection. This can occur in serial infections with pathogens sharing cross-reactive Ags. At the T cell level it has been proposed that preformed memory T cells, which cross-react with low avidity to epitopes presented in subsequent infections, dampen the response of high-avidity T cells. We investigated this with a series of related MHC class-I restricted Ags expressed by bacterial and viral pathogens. In all cases, we find that high-avidity CD8(+) T cell precursors, either naive or memory, massively expand in secondary cross-reactive infections to dominate the response over low-avidity memory T cells. This holds true even when >10% of the CD8(+) T cell compartment consists of memory T cells that cross-react weakly with the rechallenge ligand. Occasionally, memory cells generated by low-avidity stimulation in a primary infection recognize a cross-reactive epitope with high avidity and contribute positively to the response to a second infection. Taken together, our data show that the phenomenon of original antigenic sin does not occur in all heterologous infections.

Increasing the efficiency of disparity computation by interpolation

Tässä diplomityössä tutkitaan dispariteettikartan laskennan tehostamista interpoloimalla. Kolmiomittausta käyttämällä stereokuvasta muodostetaan ensin harva dispariteettikartta, jonka jälkeen koko kuvan kattava dispariteettikartta muodostetaan interpoloimalla. Kolmiomittausta varten täytyy tietää samaa reaalimaailman pistettä vastaavat kuvapisteet molemmissa kameroissa. Huolimatta siitä, että vastaavien pisteiden hakualue voidaan pienentää kahdesta ulottuvuudesta yhteen ulottuvuuteen käyttämällä esimerkiksi epipolaarista geometriaa, on laskennallisesti tehokkaampaa määrittää osa dispariteetikartasta interpoloimalla, kuin etsiä vastaavia kuvapisteitä stereokuvista. Myöskin johtuen stereonäköjärjestelmän kameroiden välisestä etäisyydestä, kaikki kuvien pisteet eivät löydy toisesta kuvasta. Näin ollen on mahdotonta määrittää koko kuvan kattavaa dispariteettikartaa pelkästään vastaavista pisteistä. Vastaavien pisteiden etsimiseen tässä työssä käytetään dynaamista ohjelmointia sekä korrelaatiomenetelmää. Reaalimaailman pinnat ovat yleisesti ottaen jatkuvia, joten geometrisessä mielessä on perusteltua approksimoida kuvien esittämiä pintoja interpoloimalla. On myöskin olemassa tieteellistä näyttöä, jonkamukaan ihmisen stereonäkö interpoloi objektien pintoja.

Challenge of transition in the socio-professional insertion of youngsters with neurodisabilities.

Objective: To evaluate the activities of patients with neurodisabilities and assess their insertion problems in the professional world. Methods: It is based on medical records of 267 patients (224 with neurodevelopmental diseases and 43 with neuromuscular diseases), aged 16-25 years, followed in the transition clinic of young adults in the neurorehabilitation services of a tertiary center. Results: Nearly half of them (46.8%) were in a protected environment, 37.08% studied and only 3.4% worked. Their studies are much longer and they are less in university than Swiss people of same age. The competitiveness criteria are no mental retardation and to be completely independent. Finally, 29.2% reported work problems, the foremost being the lack of adaptation in the workplace. Conclusion: These results highlight the need to increase the integration of young adults with neuromotor disorders in the labor market.

Co-evolutionary dynamics between public good producers and cheats in the bacterium Pseudomonas aeruginosa.

The production of beneficial public goods is common in the microbial world, and so is cheating - the exploitation of public goods by nonproducing mutants. Here, we examine co-evolutionary dynamics between cooperators and cheats and ask whether cooperators can evolve strategies to reduce the burden of exploitation, and whether cheats in turn can improve their exploitation abilities. We evolved cooperators of the bacterium Pseudomonas aeruginosa, producing the shareable iron-scavenging siderophore pyoverdine, together with cheats, defective in pyoverdine production but proficient in uptake. We found that cooperators managed to co-exist with cheats in 56% of all replicates over approximately 150 generations of experimental evolution. Growth and competition assays revealed that co-existence was fostered by a combination of general adaptions to the media and specific adaptions to the co-evolving opponent. Phenotypic screening and whole-genome resequencing of evolved clones confirmed this pattern, and suggest that cooperators became less exploitable by cheats because they significantly reduced their pyoverdine investment. Cheats, meanwhile, improved exploitation efficiency through mutations blocking the costly pyoverdine-signalling pathway. Moreover, cooperators and cheats evolved reduced motility, a pattern that likely represents adaptation to laboratory conditions, but at the same time also affects social interactions by reducing strain mixing and pyoverdine sharing. Overall, we observed parallel evolution, where co-existence of cooperators and cheats was enabled by a combination of adaptations to the abiotic and social environment and their interactions.

Magnetic Resocance Imaging Methods in the Follow-up of Multiple Sclerosis and in Farby Disease

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disorder of the central nervous system. MS is the most common disabling central nervous system (CNS) disease of young adults in the Western world. In Finland, the prevalence of MS ranges between 1/1000 and 2/1000 in different areas. Fabry disease (FD) is a rare hereditary metabolic disease due to mutation in a single gene coding α-galactosidase A (alpha-gal A) enzyme. It leads to multi-organ pathology, including cerebrovascular disease. Currently there are 44 patients with diagnosed FD in Finland. Magnetic resonance imaging (MRI) is commonly used in the diagnostics and follow-up of these diseases. The disease activity can be demonstrated by occurrence of new or Gadolinium (Gd)-enhancing lesions in routine studies. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are advanced MR sequences which can reveal pathologies in brain regions which appear normal on conventional MR images in several CNS diseases. The main focus in this study was to reveal whether whole brain apparent diffusion coefficient (ADC) analysis can be used to demonstrate MS disease activity. MS patients were investigated before and after delivery and before and after initiation of diseasemodifying treatment (DMT). In FD, DTI was used to reveal possible microstructural alterations at early timepoints when excessive signs of cerebrovascular disease are not yet visible in conventional MR sequences. Our clinical and MRI findings at 1.5T indicated that post-partum activation of the disease is an early and common phenomenon amongst mothers with MS. MRI seems to be a more sensitive method for assessing MS disease activity than the recording of relapses. However, whole brain ADC histogram analysis is of limited value in the follow-up of inflammatory conditions in a pregnancy-related setting because the pregnancy-related physiological effects on ADC overwhelm the alterations in ADC associated with MS pathology in brain tissue areas which appear normal on conventional MRI sequences. DTI reveals signs of microstructural damage in brain white matter of FD patients before excessive white matter lesion load can be observed on conventional MR scans. DTI could offer a valuable tool for monitoring the possible effects of enzyme replacement therapy in FD.

Remodeling in the ischemic heart: the stepwise progression for heart

Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI) has decreased in the last decades. However, the incidence of heart failure (HF) in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

Barriers to Service-sector SME Internationalization in the EU Business Environment

The service sector in the global world is constantly growing: in Europe, they account currently approximately for 70 per cent of the total economy. Yet service internationalization is rather a new phenomenon: services have been traditionally seen as local entities, which also explains why research on service internationalization has properly begun only few decades ago. Even though the Single European Market allows free service movement between Member States, services do not move as actively as desired: approximately only one fifth of services are involved in cross-border trade. Therefore, the main purpose of this thesis is to analyze the barriers to service-sector SME internationalization in the EU business environment. To address the research purpose, the internationalization of service-sector SMEs in the EU area is first described and thereafter, the barriers to service-sector SME internationalization in the European context are mapped and analyzed from intra- and extra-firm perspectives. In order to understand the topic area and the phenomenon, a short glance is first taken into Europe as a business environment for service industries: the market characteristics and benefits of the common free trade area for service industries are described. Also earlier literature on service internationalization and barriers to international service trade are discussed. Due to low previous research activity on barriers specifically to international service trade, the discussion is improved by presenting general findings of barriers to SME internationalization. This research is conducted with qualitative methods: there is only a limited amount of previous research and qualitative methods provide a way of gathering in-depth information and reaching understanding from respondents’ perspectives. The evidence presented in the study was collected through six semi-structured interviews with six different small or medium sized international service firm representatives that all had the first-hand knowledge regarding their company’s process of delivering services from home market to other European countries. The results of the study provide a detailed description and analysis of intra- and extra-firm barriers to service-sector SME internationalization in the context of EU and indicate that in general, internal firm-specific barriers have a greater impact in determining firm’s possibilities to be engaged in cross-border service trade – external barriers played a smaller role. What might explain these results is that first of all, the study has full focus on service firms of smaller size and internal barriers tend to be particularly effective to SMEs as their resources, skills and capabilities are often limited, which limits internationalization possibilities. Second, the results may indicate that EU’s internal market and the free trade concept function quite well from service firms’ perspective, and the low service movement rate may be rather caused by firm’s own competences and resource-related difficulties than directly by flaws in the market. The results complete earlier literature and provide new and more detailed knowledge of barriers to cross-border service trade in the context of Europe. They also indicate that service internationalization should be observed separately from internationalization of traditional manufacturing firms due to unique service-specific characteristics. The findings of this study are particularly beneficial for small or medium sized service firm managers as it provides knowledge of delivering services across borders in Europe and of barriers that relate to that process.

Solutions to water problems in the bottom of the pyramid market

Solving the water crisis in the developing world is a critical issue. Four billion people in the globe, so called the Base of the Pyramid (BoP) population suffer from inadequate access to safe drinking water, while millions die daily from waterborne diseases and lack of clean water. The BoP people desperately need to obtain a satisfactory access to safe water sources. In order to address the issue, this research has been carried out. To provide holistic consideration to the matter, comprehensive exploration of various causes of the water crisis and its impacts in developing countries were discussed. Then, various viable and relevant solutions to the problem have been thoroughly scrutinized, including scientific, rational, practical and speculative approaches, examination of existing methods, technologies and products at the BoP water market. The role of clean water to the sustainable development was specifically featured. The paper also has studied social and economic factors, actors and circumstances which affect the market development of clean water technologies in the BoP. Possibilities and potentials of successful business between foreign water enterprises and BoP consumers were considered, while primary obstacles are deliberated on, with suggestion of the ways to tackle them. Technologies and products which are needed by the poor must be affordable, sustainable and of an appropriate quality. The crucial question of technology transfer was soundly discussed with pointing out main hindrances on the way of its implementation between the developed and developing world. The means to overcome these barriers were properly observed as well. To explore to some extent the possibility and feasibility of technology transfer from Finland to the BoP sector, 3 case study analyses have been implemented. Personal discussions in form of interviews were conducted at Kemira, Outotec and Fenno Water, Finnish water treatment and supply enterprises. The results of the interviews shed light on the specific practical matters, actual obstacles and potential solutions of the technology transfer from Finland to low-income countries.

Ethics in government and business

Canadians appear to hold the activities of those in government and in big business in low esteem. Media reports of several high-profile political and corporate instances of unethical conduct have reinforced the public's concern for the status of ethical conduct and honesty in government and in big business. The response by public and private sector managers to unethical conduct by employees is largely in the form of 'ethical rules' which both sectors agree provide a measure of certainty as to the ethical conduct expected from employees. Since research on ethics in the public and private sectors is limited and since ethics is a topic of increasing concern to both sectors, this thesis provides data that could assist managers in dealing with the issue of ethical conduct within their respective organizations. The purpose of this thesis is to compare the state of ethical conduct within public and private sector organizations in Canada. This is accomplished through a description and analysis of the approaches taken by the public and private sectors as well as the four professions of law, engineering, accountancy and medicine. Ethical conduct within the public sector focuses on the ethical behaviour of public servants rather than elected officials. The underlying intent of this thesis is to discover if contemporary ethical problems are similar in the public and iv private sectors with respect to the four ethical areas of conflict of interest, political activity, problem public comment and confidentiality. The comparative data on both public and private sector ethics are assessed and similarities and differences are identified. One major finding emerges from this study. Codes of ethics in both the public and private sectors are perceived by management to play an important role in the prevention of unethical conduct. A procedure for developing a code of ethics is presented along with recommendations as to the administration of a code of ethics. Finally, recommendations are made as to the role of education in ethics.

Gender and Healing in the Hippocratic Corpus

Hippocratic physicians sought to establish themselves as medical authorities in ancient Greece. An examination of the deontological texts of the Hippocratic corpus reveals that the Hippocratics created a medical authority based on elite male characteristics. The key quality of the Hippocratic physician was sōphrosunē, a quality closely associated with men and used in the differentiation of genders in the Greek world. Women were not believed to innately possess this quality and so their healing activities were restricted within the Hippocratic framework. Women’s healing activities are only mentioned in the corpus when women are involved in the treatment of other women or self-treatment. The Hippocratic construction of medicine as a male domain fit within a Classical cultural framework, as the cultural anxiety concerning women healers and women’s use of pharmaka are evident in both Greek myth and literature.

Research Directions in Cyber Physical Systems

Cyber Physical systems (CPS) connect the physical world with cyber world. The events happening in the real world is enormous and most of it go unnoticed and information is lost. CPS enables to embed tiny smart devices to capture the data and send it to Internet for further processing. The entire set-up call for lots of challenges and open new research problems. This talk is a journey through the landscape of research problems in this emerging area.

Convectively coupled equatorial waves in high resolution Hadley centre climate models

Current global atmospheric models fail to simulate well organised tropical phenomena in which convection interacts with dynamics and physics. A new methodology to identify convectively coupled equatorial waves, developed by NCAS-Climate, has been applied to output from the two latest models of the Met Office/Hadley Centre which have fundamental differences in dynamical formulation. Variability, horizontal and vertical structures, and propagation characteristics of tropical convection and equatorial waves, along with their coupled behaviour in the models are examined and evaluated against a previous comprehensive study of observations. It is shown that, in general, the models perform well for equatorial waves coupled with off-equatorial convection. However they perform poorly for waves coupled with equatorial convection. The vertical structure of the simulated wave is not conducive to energy conversion/growth and does not support the correct physical-dynamical coupling that occurs in the real world. The following figure shows an example of the Kelvin wave coupled with equatorial convection. It shows that the models fail to simulate a key feature of convectively coupled Kelvin wave in observations, namely near surface anomalous equatorial zonal winds together with intensified equatorial convection and westerly winds in phase with the convection. The models are also not able to capture the observed vertical tilt structure and the vertical propagation of the Kelvin wave into the lower stratosphere as well as the secondary peak in the mid-troposphere, particularly in HadAM3. These results can be used to provide a test-bed for experimentation to improve the coupling of physics and dynamics in climate and weather models.