The conservative physiology of the immune system

Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies). Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation) is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn's syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.

Ethanol-induced colitis prevents oral tolerance induction in mice

The gut mucosa is a major site of contact with antigens from food and microbiota. Usually, these daily contacts with natural antigens do not result in inflammatory reactions; instead they result in a state of systemic hyporesponsiveness named oral tolerance. Inflammatory bowel diseases (IBD) are associated with the breakdown of the immunoregulatory mechanisms that maintain oral tolerance. Several animal models of IBD/colitis are available. In mice, these include targeted disruptions of the genes encoding cytokines, T cell subsets or signaling proteins. Colitis can also be induced by intrarectal administration of chemical substances such as 2,4,6-trinitrobenzene sulfonic acid in 50% ethanol. We report here a novel model of colitis induced by intrarectal administration of 50% ethanol alone. Ethanol-treated mice develop an inflammatory reaction in the colon characterized by an intense inflammatory infiltrate in the mucosa and submucosa of the large intestine. They also present up-regulation of both interferon gamma (IFN-gamma) and interleukin-4 (IL-4) production by cecal lymph node and splenic cells. These results suggest a mixed type of inflammation as the substrate of the colitis. Interestingly, cells from mesenteric lymph nodes of ethanol-treated mice present an increase in IFN-gamma production and a decrease in IL-4 production indicating that the cytokine balance is altered throughout the gut mucosa. Moreover, induction of oral tolerance to ovalbumin is abolished in these animals, strongly suggesting that ethanol-induced colitis interferes with immunoregulatory mechanisms in the intestinal mucosa. This novel model of colitis resembles human IBD. It is easy to reproduce and may help us to understand the mechanisms involved in IBD pathogenesis.

Pressure-induced dissociation of casein micelles: size distribution and effect of temperature

Pressure-induced dissociation of a turbid solution of casein micelles was studied in situ in static and dynamic light scattering experiments. We show that at high pressure casein micelles decompose into small fragments comparable in size to casein monomers. At intermediate pressure we observe particles measuring 15 to 20 nm in diameter. The stability against pressure dissociation increased with temperature, suggesting enhanced hydrophobic contacts. The pressure transition curves are biphasic, compatible with a temperature (but not pressure)-dependent conformational equilibrium of two micelle species. Our thermodynamic model predicts an increase in structural entropy with temperature.

Early Life Intestinal Microbiota in Health and in Atopic Eczema

Decrease in microbial contacts in affluent societies is considered to lie behind the rise in allergic and other chronic inflammatory diseases during the last decades. Indeed, deviations in the intestinal microbiota composition and diversity have been associated with several diseases, such as atopic eczema. However, there is no consensus yet on what would constitute a beneficial or harmful microbiota. The aim of this thesis was to study the microbiota development in healthy infants and to characterize intestinal microbiota signatures associated with disease status and severity in infants with atopic eczema. The methodological aim was to compare and optimize methods for DNA extraction from fecal samples to be used in high-throughput microbiota analyses. It was confirmed that the most critical step in successful microbial DNA extraction from fecal samples is the mechanical cell lysis procedure. Based on this finding, an efficient semi-automated extraction process was developed that can be scaled for use in high-throughput platforms such as phylogenetic microarray used in this series of studies. By analyzing a longitudinal motherchild cohort for 3 years it was observed that the microbiota development is a gradual process, where some bacterial groups reach the degree of adult-type pattern earlier than others. During the breast-feeding period, the microbiota appeared to be relatively simple, while major diversification was found to start during the weaning process. By the age of 3 years, the child’s microbiota composition started to resemble that of an adult, but the bacterial diversity has still not reached the full diversity, indicating that the microbiota maturation extends beyond this age. In addition, at three years of age, the child’s microbiota was more similar to mother’s microbiota than to microbiota of nonrelated women.In infants with atopic eczema, a high total microbiota diversity and abundance of butyrate-producing bacteria was found to correlate with mild symptoms at 6 months. At 18 months, infants with mild eczema had significantly higher microbiota diversity and aberrant microbiota composition when compared to healthy controls at the same age. In conclusion, the comprehensive phylogenetic microarray analysis of early life microbiota shows the synergetic effect of vertical transmission and shared environment on the intestinal microbiota development. By the age of three years, the compositional development of intestinal microbiota is close to adult level, but the microbiota diversification continues beyond this age. In addition, specific microbiota signatures are associated with the existence and severity of atopic eczema and intestinal microbiota seems to have a role in alleviating the symptoms of this disease.

Solid-state reference and ion-selective electrodes : towards portable potentiometric sensing

Potentiometric sensors are very attractive tools for chemical analysis because of their simplicity, low power consumption and low cost. They are extensively used in clinical diagnostics and in environmental monitoring. Modern applications of both fields require improvements in the conventional construction and in the performance of the potentiometric sensors, as the trends are towards portable, on-site diagnostics and autonomous sensing in remote locations. The aim of this PhD work was to improve some of the sensor properties that currently hamper the implementation of the potentiometric sensors in modern applications. The first part of the work was concentrated on the development of a solid-state reference electrode (RE) compatible with already existing solid-contact ion-selective electrodes (ISE), both of which are needed for all-solid-state potentiometric sensing systems. A poly(vinyl chloride) membrane doped with a moderately lipophilic salt, tetrabutylammonium-tetrabutylborate (TBA-TBB), was found to show a satisfactory stability of potential in sample solutions with different concentrations. Its response time was nevertheless slow, as it required several minutes to reach the equilibrium. The TBA-TBB membrane RE worked well together with solid-state ISEs in several different situations and on different substrates enabling a miniature design. Solid contacts (SC) that mediate the ion-to-electron transduction are crucial components of well-functioning potentiometric sensors. This transduction process converting the ionic conduction of an ion-selective membrane to the electronic conduction in the circuit was studied with the help of electrochemical impedance spectroscopy (EIS). The solid contacts studied were (i) the conducting polymer (CP) poly(3,4-ethylienedioxythiophene) (PEDOT) and (ii) a carbon cloth having a high surface area. The PEDOT films were doped with a large immobile anion poly(styrene sulfonate) (PSS-) or with a small mobile anion Cl-. As could be expected, the studied PEDOT solid-contact mediated the ion-toelectron transduction more efficiently than the bare glassy carbon substrate, onto which they were electropolymerized, while the impedance of the PEDOT films depended on the mobility of the doping ion and on the ions in the electrolyte. The carbon cloth was found to be an even more effective ion-to-electron transducer than the PEDOT films and it also proved to work as a combined electrical conductor and solid contact when covered with an ion-selective membrane or with a TBA-TBB-based reference membrane. The last part of the work was focused on improving the reproducibility and the potential stability of the SC-ISEs, a problem that culminates to the stability of the standard potential E°. It was proven that the E° of a SC-ISE with a conducting polymer as a solid contact could be adjusted by reducing or oxidizing the CP solid contact by applying current pulses or a potential to it, as the redox state of the CP solid-contact influences the overall potential of the ISE. The slope and thus the analytical performance of the SC-ISEs were retained despite the adjustment of the E°. The shortcircuiting of the SC-ISE with a conventional large-capacitance RE was found to be a feasible instrument-free method to control the E°. With this method, the driving force for the oxidation/reduction of the CP was the potential difference between the RE and the SC-ISE, and the position of the adjusted potential could be controlled by choosing a suitable concentration for the short-circuiting electrolyte. The piece-to-piece reproducibility of the adjusted potential was promising, and the day-today reproducibility for a specific sensor was excellent. The instrumentfree approach to control the E° is very attractive considering practical applications.

Immunoglobulin production is impaired in protein-deprived mice and can be restored by dietary protein supplementation

Most contacts with food protein and microbiota antigens occur at the level of the gut mucosa. In animal models where this natural stimulation is absent, such as germ-free and antigen-free mice, the gut-associated lymphoid tissue (GALT) and systemic immunological activities are underdeveloped. We have shown that food proteins play a critical role in the full development of the immune system. C57BL/6 mice weaned to a diet in which intact proteins are replaced by equivalent amounts of amino acids (Aa diet) have a poorly developed GALT as well as low levels of serum immunoglobulins (total Ig, IgG, and IgA, but not IgM). In the present study, we evaluated whether the introduction of a protein-containing diet in 10 adult Aa-fed C57BL/6 mice could restore their immunoglobulin levels and whether this recovery was dependent on the amount of dietary protein. After the introduction of a casein-containing diet, Aa-fed mice presented a fast recovery (after 7 days) of secretory IgA (from 0.33 to 0.75 mg/mL, while in casein-fed mice this value was 0.81 mg/mL) and serum immunoglobulin levels (from 5.39 to 10.25 mg/mL of total Ig). Five percent dietary casein was enough to promote the restoration of secretory IgA and serum immunoglobulin levels to a normal range after 30 days feeding casein diet (as in casein-fed mice - 15% by weight of diet). These data suggest that the defect detected in the immunoglobulin levels was a reversible result of the absence of food proteins as an antigenic stimulus. They also indicate that the deleterious consequences of malnutrition at an early age for some immune functions may be restored by therapeutic intervention later in life.

Jöns Budde och hans skrifter – yngre fornsvenskt textmaterial och mannen bakom det

Tutkielman aiheena on kieli ja tyyli Jöns Budden latinasta muinaisruotsiksi kääntämissä teksteissä. Tarkoituksena on tutkia, millaisia tekstejä Budde käänsi ja missä tarkoituksessa. Lisäksi tutkin kielikontakteja latinaan ja saksaan sekä Buddea henkilönä hänen tuotantonsa valossa. Arvioin myös aiempien Buddeen liittyvien hypoteesien paikkansapitävyyttä. Materiaali käsittää kaikki tekstit, joiden yleisesti oletetaan olevan Budden kääntämiä. Osa on anonyymejä, mutta niiden yhteys Buddeen on erittäin todennäköinen. Aineisto käsittää noin 1350 sivua painetuissa editioissa. Tutkimus on materiaalilähtöistä: tarkan tekstinluvun ja teksti-interpretaation kautta olen kiinnittänyt huomioni erilaisiin etupäässä tyylillisiin seikkoihin, joita kommentoin ottaen huomioon kulttuurihistoriallisen kontekstin. Tutkimus kohdistuu kielenkäyttöön tietyssä konkreettisessa materiaalissa eli tarkastelun kohteina ovat parole ja synkronia ensisijaisemmin kuin diakronia ja langue eli kieli systeeminä ja resurssina. Metodina on siten filologinen teksti-interpretaatio, ja tutkimus on kommentaari Budden teksteihin. Keskeinen tulos on, että Budde on tietoinen stilisti, joka käyttää kieliopin ja stilistiikan keinoja sisällöllisten asioiden painottamiseen ja dramatisointiin. Budden tyyli-ihanteilla on suureksi osaksi esikuvia latinassa, mutta Budde ei noudata niitä orjallisen sokeasti, vaan on itsenäinen alkuteksteihin nähden. Toinen merkittävä tulos liittyy Budden kääntämien Raamatun kirjojen tarkoitukseen. Käsitykseni mukaan niitä ei ole tarkoitettu luettaviksi sellaisenaan, vaan apuvälineiksi luettaessa varsinaista pyhää kirjaa eli Vulgataa latinaksi. Tekstien tekijyyteen liittyvät aiemmat hypoteesit saavat tukea tutkimuksestani, kun taas Budden aristokraattisiin yhteyksiin ja hänen mahdollisiin opintoihinsa Saksassa liittyvät hypoteesit osoittautuvat liian rohkeiksi ottaen huomioon säilyneiden lähteiden niukkuuden.

Studies of rotor dynamics using a multibody simulation approach

The non-idealities in a rotor-bearing system may cause undesirable subcritical superharmonic resonances that occur when the rotating speed of the rotor is a fraction of the natural frequency of the system. These resonances arise partly from the non-idealities of the bearings. This study introduces a novel simulation approach that can be used to study the superharmonic vibrations of rotor-bearing systems. The superharmonic vibrations of complex rotor-bearing systems can be studied in an accurate manner by combining a detailed rotor and bearing model in a multibody simulation approach. The research looks at the theoretical background of multibody formulations that can be used in the dynamic analysis of flexible rotors. The multibody formulations currently in use are suitable for linear deformation analysis only. However, nonlinear formulation may arise in high-speed rotor dynamics applications due to the cenrrifugal stiffening effect. For this reason, finite element formulations that can describe nonlinear deformation are also introduced in this work. The description of the elastic forces in the absolute nodal coordinate formulation is studied and improved. A ball bearing model that includes localized and distributed defects is developed in this study. This bearing model could be used in rotor dynamics or multibody code as an interface elements between the rotor and the supporting structure. The model includes descriptions of the nonlinear Hertzian contact deformation and the elastohydrodynamic fluid film. The simulation approaches and models developed here are applied in the analysis of two example rotor-bearing systems. The first example is an electric motor supported by two ball bearings and the second is a roller test rig that consists of the tube roll of a paper machine supported by a hard-bearing-type balanceing machine. The simulation results are compared to the results available in literature as well as to those obtained by measuring the existing structure. In both practical examples, the comparison shows that the simulation model is capable of predicting the realistic responses of a rotor system. The simulation approaches developed in this work can be used in the analysis of the superharmonic vibrations of general rotor-bearing systems.

From epithelial to mesenchymal: regulation of invasive cancer cell motility

Metastasis is the main cause of death among cancer patients. In order to initiate the metastatic cascade cancer cells have to undergo epithelial-to-mesenchymal transition (EMT). In EMT epithelial cells lose their cell-cell and cell-extracellular matrix (ECM) contacts and become more motile. The expression of the transcription factor Slug and of the mesenchymal intermediate filament vimentin is induced during EMT. Vimentin is often overexpressed in malignant epithelial cancers but the functional role of vimentin remains incompletely understood. In addition, kinases such as AKT and ERK are known to be involved in the regulation of EMT and cancer cell motility but the mechanisms underlining their functions are often unclear. Integrins are heterodimeric receptors that attach cells to the surrounding tissue and participate in regulating cell migration and invasion. Changes in integrin activity are linked to increased cell motility and further cancer metastasis. The aim for my PhD studies was to investigate the role of cellular signalling pathways and vimentin in the regulation of cancer cell motility and EMT. Our results revealed that in prostate cancer the downregulation of AKT1 and AKT2, but not AKT3, induces activation of cell surface 1-integrins leading to enhanced cell adhesion, migration and invasion. In addition, our findings demonstrated a reciprocal regulatory interaction between vimentin and ERK2 facilitating ERK-mediated phosphorylation of Slug at serine-87 (S87) in breast cancer. Surprisingly, Slug S87 phosphorylation is dispensable for E-cadherin repression but essential for the induction of vimentin and Axl expression in early onset of EMT. Our findings reveal previously unknown mechanistic information of how prostate and breast cancer cell motility and disease progression is regulated

Grassroots Charity in China: Case Analysis of a Charity Project Organised by Jane Zhang Fan Club

As unregistered grassroots charities do not appear in official statistics in China, they tend to remain unnoticed by scholars. Also as they operate unofficially and avoid publicity, their work is usually not reported by the media. In this research I explore the grassroots charity activity of one pop music fan club from the viewpoint of trust as a sociological concept. I will also establish the general situation on charity in China. By using textual analysis on internet blogs and discussion forums I map the charity project from the discussion of the original idea to the execution and follow up phase. I study the roles the fan club members assume during the project as anonymous participants of internet conversations, as well as concrete active charity volunteers outside of the virtual world. I establish parties, other than the fan club, which are involved in the charity project. Interviews with one of the participant of the project in 2010, 2014 and 2015 bring valuable additional information and help in distributing the questionnaire survey. A quantitative questionnaire survey was distributed among the fan club members to get more detailed information on the motives and attitudes towards official and unofficial charity in China. Because of the inequality in China, the rural minority areas do not have similar educational opportunities as the mostly majority inhabited urban areas, even though the country officially has a nine year compulsory education. Grassroots charities can operate in relative freedom taking some of the government’s burden of social responsibilities if they are not criticizing the authorities. The problem with grassroots charity seems to be lack of sustainability. The lack of trust for authorities and official charities was the reason why the Jane Zhang fan club decided to conduct a charity case unofficially. As a group of people previously unknown to each other, they managed to build mutual trust to carry out the project transparently and successfully, though not sustainably. The internet has provided a new and effective platform for unofficial grassroots charities, who choose not to co-operate with official organisations. On grassroots level charities can have the transparency and trust that lack from official charities. I suggest, that interviewing the real persons behind the internet aliases and finding out what happened outside the discussion forums, would bring a more detailed and outspoken description of the project concerning of the contacts with the local authorities. Also travelling to the site and communicating with the local people in the village would establish how they have experienced the project.

Exploring knowledge worker motivation in autonomous and interdependent problem solving tasks on virtual platforms

The objective of this study is to understand why virtual knowledge workers conduct autonomous tasks and interdependent problem solving tasks on virtual platforms. The study is qualitative case study including three case organizations that tap the knowledge of expert networks, and utilize virtual platforms in the work processes. Research data includes 15 interviews, that is, five experts from each case company. According to the findings there are some specific characteristics in motivation to work on tasks on online platforms. Autonomy, self-improvement, meaningful tasks, knowledge sharing, time management, variety of contacts, and variety of tasks, and projects motivate virtual knowledge workers. Factors that may enhance individuals’ engagement to work on tasks are trust, security of continuous task flow and income, feedback, meaningful tasks and tasks that contribute to self-improvement, flexibility and effectiveness in time management, and virtual tools that support social interaction. The results also indicate that there are some differences in individuals’ motivation based on the tasks’ nature. That is, knowledge sharing and variety of contacts motivated experts who worked on interdependent problem solving tasks. Then again, autonomy and variety of tasks motivated experts who worked on autonomous tasks.

Expressing the self in postmodern travel consumption: a case study of students

The study approaches student travel from the perspective of postmodern consumption. The background is in the observation that the student travel market has a vast potential, but it is not necessarily capitalized upon to the extent it could. This might partly have to do with the peculiarities of postmodernity: consumption is characterized by unpredictability and abstract motives. The research questions are built around what constitutes student travel consumption and how can students be categorized according to motivation, behaviour and values. Also identity and expressiveness are present and it is evaluated, if travel services facilitate these background is the observation that the student travel market has a vast potential, but it is not necessarily capitalized upon to the extent it could be. This might partly have to do with the peculiarities of postmodernity: consumption is characterized by unpredictability and abstract motives. The research questions are built around what constitutes student travel consumption and how can students be categorized according to motivation, behaviour and values. Also identity and expressiveness are present and it is evaluated whether travel services facilitate these constructs. The topic is approached by discovering the key concepts such as self-identity. This was done in order to create survey questions that reflect the underlying theories. The survey was sent to chosen student groups of Turku School of Economics. The data was analyzed using statistical methods, mainly principal component analysis, in order to categorize students’ motives and behaviour into distinct profiles. The findings indicate that students have a high level of awareness in their travel consumption choices. Travel services seem to facilitate identity and lifestyle expressiveness, one central dimension of postmodernity. Psychographics such as motivation seem to work well as a segmentation criteria when it comes to the student traveler market. Travel offers students an opportunity for relaxation, escape, enjoyment and gaining new experiences and social contacts. Furthermore, the enjoyment of the travel experience extends to the pre- and post-trip time.

How to reach more potential global b2b customers to Finnish high tech company websites

This thesis examines the optimization of a website in terms of creating website visibility and interesting and attractive online information, with the aim of finding ways how the case company can increase the number of online visitors for the websites, who would even-tually contact the case company, and become customers. The theoretical part concentrates on website visibility, academic knowledge about search engine optimization, integrated marketing communications, website effectiveness and influence tactics (mostly non-coercive) in an online b2b buying context. The empirical part included an experiment of two weeks on the case website. Search engine optimization requires the most relevant key terms and keywords to be selected and carefully implemented to meta descriptions of the most informational pages. The information visible to visitors on these pages was also opti-mized to make it interesting and purposeful for the targeted audience. The most suitable influence tactics were implemented to certain pages to attract the website visitors to con-tact the case company. The results suggest that relevant key terms in meta descriptions do improve, or maintain the same high, ranking a page has on search engine result pages, but this is not directly connected to the amount of visitors to the website. The number of visi-tors does not either affect the amount of customer contacts the company received during the experiment period.

Business leadership in the classroom

This action research assesses a framework that assists business educators in promoting leadership within a classroom. It is designed to better prepare students to assume leadership and fill the "leadership gap" in business. Two classes of 2nd-year community college business students participated in running and managing their own business community as teams of sales professionals by developing and practicing their own individual leadership for 28 weeks during their sales courses. The intent was to assess the development of leadership resulting from the implementation of the "Business Leadership in the Classroom" framework. This framework balances leadership principles to simulate a business environment with the practical elements of a learning community under the facilitation of an experienced business educator. The action research approach was used to assess and adjust approaches to business leadership on a continuous basis throughout the research. Data were collected from 61 students based on journals, surveys, peer group reviews, and my (facilitator) reflective journal.The findings reveal that both individual and collective business leadership views and practical skills developed over time. A business leadership mind-set evolved that ranged from a general awareness of the importance of leadership, to a conscious and deliberate use of individual leadership. Areas important in building a progression of leadership included: leadership teams, membership roles, weekly leadership teams, peer feedback, and activity-based learning. Emerging themes included leadership, leadership style, teamwork, as well as influence and motivation. The research framework was effective in supporting the development of business leadership but required some adjustments. These included increased structure and feedback mechanisms. Interpretation of the findings demonstrates the importance of real-world practical education in the classroom. Results show how focusing on a single mind-set such as business leadership, can result in enormous individual growth and development. When business students are encouraged to act as real businesspeople, managing their own learning, the results are effective in preparing them for the business world. All participants expressed their leadership in different ways based on personality and individual strengths. There was an overwhelming and, in some cases, passionate interest in leadership. The use of action research with a range of data collection methods provides a way to measure and track individual student learning and to generate adjustments to the research framework design and learning approaches. The findings generate implications and recommendations to continue this research further. Key recommendations center around how to ensure leadership development is sustained, including improved approaches to heighten the real-world feel of the classroom. Specifically, the use of leadership goals and action plans for each individual participant and an active use of outside business resource people as contacts for participants is recommended.

Education in the halls : students' perspectives on cultural expression and resistance

This research is a qualitative study of cultural reproduction and resistance from students' perspectives. Thirteen teenagers (eight in attendance in regular high schools and five drop-outs) were recruited to take part and were involved to varying degrees through interviews, journal writing, and group interactive sessions. A purposive sampling design was used initially to recruit individuals known to the researcher through contacts in an alternate education setting. Other participants were recruited throughout the research phase. The theoretical aspects are premised on the work of Paul Willis, Michel Foucault, and Pierre Bourdieu. The reflexive praxeology of Bourdieu reflects the position taken as one way of understanding how students construct and respond to the situations of cultural dominance they experience in schools. The same reflexivity is offered for suggestions as to how teachers can respond to their own position in the education system.