Therapeutic Properties of Superoxide Dismutase 3 and Mesenchymal Stromal Cells in Peripheral Ischemia

The aim of this study was to characterize the cellular mechanisms leading to the beneficial effect of anti-oxidative gene therapy and pro-angiogenic stem cell therapy in acute peripheral ischemia. Post-ischemic events aim to re-establish tissue blood perfusion, to clear cellular debris, and to regenerate lost tissue by differentiation of satellite cells into myoblasts. Although leukocytes have an essential role in clearing cellular debris and promoting angiogenesis, they also contribute to tissue injury through excessive ROS production. First, we investigated the therapeutic properties of extracellular superoxide dismutase (SOD3) gene transfer. SOD3 was shown to reduce oxidative stress, to normalize glucose metabolism, and to enhance cell proliferation in the ischemic muscle. Analysis of the mitogenic Ras-Erk1/2 pathway showed SOD3 mediated induction offering a plausible explanation for enhanced cell proliferation. In addition, SOD3 reduced NF-κB activity by enhancing IκBα expression thus leading to reduced expression of inflammatory cytokines and adhesion molecules with consequent reduction in macrophage infiltration. Secondly, we sought to determine the fate and the effect of locally transplanted mesenchymal stem/stromal cells (MSCs) in acute ischemia. We showed that a vast majority of the transplanted cells are cleared from the injury site within 24 hours after local transplantation. Despite rapid clearance, transplantation was able to temporarily promote angiogenesis and cell proliferation in the muscle. Lack of graft-derived growth factor expression suggests other than secretory function to mediate this observed effect. In conclusion, both SOD3 and MSCs could be utilized to alleviate peripheral ischemia induced tissue injury. We have described a previously unidentified growth regulatory role for SOD3, and suggest a novel mechanism whereby transplanted MSCs enhance the reparative potential of the recipient tissue through physical contacts.

The relativity of evaluative sentences: disagreeing over disagreement

Evaluative sentences (moral judgments, expressions of taste, epistemic modals) are relative to the speaker's standards. Lately, a phenomenon has challenged the traditional explanation of this relativity: whenever two speakers disagree over them they contradict each other without being at fault. Hence, it is thought that the correction of the assertions involved must be relative to an unprivileged standard not necessarily the speaker's. I will claim instead that so far, neither this nor any other proposal has provided an explanation of the phenomenon. I will point out several problems presented by them and I will hint to how this phenomenon could be explained by making minor adjustments to our semantic theory.

Analysis on firm innovation boundaries

Innovation has been widely recognized as an important driver of firm competitiveness, and the firm’s internal research and development (R&D) activities are often considered to have a critical role in innovation activities. Internal R&D is, however, not the source of innovation as firms may tap into knowledge necessary for innovation also through various types of sourcing agreements or by collaborating with other organizations. The objective of this study is to analyze the way firms go about organizing efficiently their innovation boundaries. Within this context, the analysis is focused, firstly, on the relation between innovation boundaries and firm innovation performance and, secondly, on the factors explaining innovation boundary organization. The innovation literature recognizes that the sources of innovation depend on the nature of technology but does not offer a sufficient tool for analyzing innovation boundary options and their efficiency. Thus, this study suggests incorporating insights from transaction cost economics (TCE) complemented with dynamic governance costs and benefits into the analysis. The thesis consists of two parts. The first part introduces the background of the study, research objectives, an overview of the empirical studies, and the general conclusions of the study. The second part is formed of five publications. The overall results firstly indicate that although the relation between firm innovation boundary options is partly industry sector-specific, the firm level search strategies and knowledge transfer capabilities are important for innovation performance independently of the sector. Secondly, the results show that the attributes suggested by TCE alone do not offer a sufficient explanation of innovation boundary selection, especially under conditions of high levels of (radical) uncertainty. Based on the results, the dynamic governance cost and benefit framework complements the static TCE when firm innovation boundaries are scrutinized.

General terms and rigidity: another solution to the trivialization problem

In this paper I am concerned with the problem of applying the notion of rigidity to general terms. In Naming and Necessity, Kripke has clearly suggested that we should include some general terms among the rigid ones, namely, those common nouns semantically correlated with natural substances, species and phenomena, in general, natural kinds -'water', 'tiger', 'heat'- and some adjectives -'red', 'hot', 'loud'. However, the notion of rigidity has been defined for singular terms; after all, the notion that Kripke has provided us with is the notion of a rigid designator. But general terms do not designate single individuals: rather, they apply to many of them. In sum, the original concept of rigidity cannot be straightforwardly applied to general terms: it has to be somehow redefined in order to make it cover them. As is known, two main positions have been put forward to accomplish that task: the identity of designation conception, according to which a rigid general term is one that designates the same property or kind in all possible worlds, and the essentialist conception, which conceives of a rigid general term as an essentialist one, namely, a term that expresses an essential property of an object. My purpose in the present paper is to defend a particular version of the identity of designation conception: on the proposed approach, a rigid general term will be one that expresses the same property in all possible worlds and names the property it expresses. In my opinion, the position can be established on the basis of an inference to the best explanation of our intuitive interpretation and evaluation, relative to counterfactual circumstances, of statements containing different kinds of general terms, which is strictly analogous to our intuitive interpretation and evaluation, relative to such circumstances, of statements containing different kinds of singular ones. I will argue that it is possible to offer a new solution to the trivialization problem that is thought to threaten all versions of the identity of designation conception of rigidity. Finally, I will also sketch a solution to the so-called 'over-generalization and under-generalization problems', both closely related to the above-mentioned one.

A SECOND OPINION ON RELATIVE TRUTH

In 'An undermining diagnosis of relativism about truth', Horwich claims that the notion of relative truth is either explanatorily sterile or explanatorily superfluous. In the present paper, I argue that Horwich's explanatory demands set the bar unwarrantedly high: given the philosophical import of the theorems of a truth-theoretic semantic theory, Horwich's proposed explananda, what he calls acceptance facts, are too indirect for us to expect a complete explanation of them in terms of the deliverances of a theory of meaning based on the notion of relative truth. And, to the extent that there might be such an explanation in certain cases, there is no reason to expect relative truth to play an essential, ineliminable role, nor to endorse the claim that it should play such a role in order to be a theoretically useful notion.

Kaukojäähdytyksen potentiaali ja kannattavuus Oulun keskustan alueella

Diplomityö on tehty Oulun Energian kaukolämpöosastolle. Työn tavoitteena oli selvittää kaukojäähdytyksen asiakaspotentiaali Oulun keskustan alueella sekä tehdä esiselvitys kaukojäähdytysinvestoinnin kannattavuudesta. Potentiaalin kartoituksessa otettiin huomioon sekä nykyiset rakennukset että lähitulevaisuuden lisärakentaminen. Jäähdytyskuormaksi Oulun keskustassa saatiin 28 MW, josta suurin osa on liiketiloja, toimistorakennuksia sekä hotelleja. Investoinnin kannattavuutta tutkittiin perinteisillä investointilaskennan menetelmillä. Kustannusarvio perustuu vapaajäähdytykseen ja absorptiojäähdytykseen ja tuotantolaitoksen sijoittamiseen kalliotiloihin. Tuottojen arviointia varten määriteltiin alustava kaukojäähdytystariffi sekä kolme erilaista kasvumallia. Tulosten perusteella investointi vaikuttaisi kannattamattomalta. Pääsyynä kannattamattomuuteen on kallis alkuinvestointi, jossa etenkin louhinnan osuus on merkittävä. Toisena syynä kannattamattomuuteen voidaan pitää potentiaalisten kaukojäähdytykseen liitettävien rakennusten melko pientä kokoa Oulun keskustassa.

Momentum-anomalia ja siihen perustuvat sijoitusstrategiat Yhdysvaltojen osakemarkkinoilla

Tutkielmassa lähestytään osakemarkkinoilla havaittua poikkeavuutta, momentum-anomaliaa, sekä sen ilmenemistä ja selittyvyyttä Yhdysvaltojen osakemarkkinoiden olosuhteissa. Lisäksi tutkielma sisältää lyhyen katsauksen kansainvälisesti ilmenevään momentumiin kuin myös sen muodostumiseen vaikuttaviin tekijöihin. Työn tutkimusongelmana on, selittyykö Yhdysvaltojen osakemarkkinoilla ilmenevä momentum-anomalia selkeämmin behaviorististen vai makrotaloudellisten riskitekijöiden muodostamien mallien avulla. Kuten aiempi tutkimus on havainnut, myös tässä tutkielmassa oletuksena on, että behavioristis-perusteiset tekijät omaavat suuremman selitysvoiman, kuin makrotaloudellisten riskitekijöiden -perusteiset mallit. Yksittäisiin tekijöihin keskittymisen ohella on tarkoitus havainnoida momentum-anomalian ilmentymisen riippuvuus markkinasuhdanteista, jolloin syntyviä momentumin tuottoja tarkastellaan sekä korkea-, että matalasuhdannemarkkinoiden olosuhteissa.

"Kadonneen realistisuuden metsästäjä"

Kirjallisuusarvostelu

Leda förändring genom relationer, processer och kultur

Forskningens syfte var att bidra med en ny kunskapssyntes om vad det innebär att leda förändring ur ett vårdvetenskapligt perspektiv. Vårdledaren har, speciellt vid större förändringar inom organisationen, en stor betydelse för hur vårdandet förvaltas genom att hålla den vårdande traditionen levande och genom formningen av den vårdande kulturen och vårdgemenskapen. Den övergripande hermeneutiska forskningsansatsen med tillämpning av metodologisk triangulering har influerats av Gadamers, Ricoeurs och Ödmans syn på hermeneutik med förståelse och förklaring som kompletterar varandra. Forskningens övergripande frågeställning ”Vad innebär det att leda förändring ur ett vårdvetenskapligt perspektiv?” förankrades i de fyra underliggande frågeställningarna. Den första frågeställningen berörde meningsinnehållet i begreppet förändring samt dess gestaltning. Metoden var en hermeneutisk begreppsbestämning på en ontologisk och kontextuell nivå enligt Koorts metod för begreppsbestämning. Genom en personalenkät undersöktes personalens åsikter (totalt 597 personer) om den kommande fusionen och förändringen samt deras förväntningar på ledarna under förändringsprocessen för att få svar på vad förutsättningarna var för en förändring eller förändringsprocess med avsedda mål och effekter. Svaret på hur vårdledaren och dennes uppgifter gestaltades vid en förändring samt hur vårdledarna uppfattade förändring och den kommande förändringsprocessen erhölls genom djupintervjuer med vårdledare (17). Av resultatet framgår att vårdledaren leder förändring genom att leda relationer, processer och kultur och genom ett stödjande, reflekterande och kulturbärande ledarskap med syftet att åstadkomma en verklig och hållbar förändring. För att åstadkomma en verklig och hållbar förändring, dvs. en inre omgestaltning och omdaning som vardande, förutsätts dock att både tankemönster och handlanden förändras. Riktningen och insatserna för förändringen skall ha sin grund i en tydlig och meningsfull målsättning och vision utgående från en gemensam värdegrund. En arena för dialog borde utvecklas så att förändringens liksom även vårdandets vision och mission förankras och utvecklas till handling och förändring. Vårdledarens primära uppgift eller mission var att tillhandahålla varje individuell patient en god vård. Den primära missionen var med andra ord att med ansvarsfullhet tjäna vårdandet sak utgående från ett etiskt förhållningssätt. I tjänande av vårdandets sak fanns dock en tillit till att förändringen gagnar patienten och hans eller hennes vård, men vårdledarnas anpassning till förändringen var utan djupare engagemang. Vårdledarna kände även en oro för sitt uppdrag som vårdledare, vårdarbetets ställning och mandatet som patientens advokat. Vårdledaren är också en kulturbärare, vilket innebär att även kulturen har betydelse under en förändringsprocess. Genom att leda kulturen skapar vårdledaren en öppen, bekräftande och evidensbaserad atmosfär med centrala värderingar som ger uttryck för den rådande andan och kulturen.

Social ventures : the development of the theory of sustainable contributive advantage and initial empirical tests

This thesis attempts to fill gaps in both a theoretical basis and an operational and strategic understanding in the areas of social ventures, social entrepreneurship and nonprofit business models. This study also attempts to bridge the gap in strategic and economic theory between social and commercial ventures. More specifically, this thesis explores sustainable competitive advantage from a resource-based theory perspective and explores how it may be applied to the nonmarket situation of nonprofit organizations and social ventures. It is proposed that a social value-orientation of sustainable competitive advantage, called sustainable contributive advantage, provides a more realistic depiction of what is necessary in order for a social venture to perform better than its competitors over time. In addition to providing this realistic depiction, this research provides a substantial theoretical contribution in the area of economics, social ventures, and strategy research, specifically in regards to resource-based theory. The proposed model for sustainable contributive advantage uses resource-based theory and competitive advantage in order to be applicable to social ventures. This model proposes an explanation of a social venture’s ability to demonstrate consistently superior performance. In order to determine whether sustainable competitive advantage is in fact, appropriate to apply to both social and economic environments, quantitative analyses are conducted on a large sample of nonprofit organizations in a single industry and then compared to similar quantitative analyses conducted on commercial ventures. In comparing the trends and strategies between the two types of entities from a quantitative perspective, propositions are developed regarding a social venture’s resource utilization strategies and their possible impact on performance. Evidence is found to support the necessity of adjusting existing models in resource-based theory in order to apply them to social ventures. Additionally supported is the proposed theory of sustainable contributive advantage. The thesis concludes with recommendations for practitioners, researchers and policy makers as well as suggestions for future research paths.

Theoretical Analysis and Numerical Simulation of Spectral Radiative Properties of Combustion Gases in Oxy/Air-Fired Combustion Systems

Energy efficiency is one of the major objectives which should be achieved in order to implement the limited energy resources of the world in a sustainable way. Since radiative heat transfer is the dominant heat transfer mechanism in most of fossil fuel combustion systems, more accurate insight and models may cause improvement in the energy efficiency of the new designed combustion systems. The radiative properties of combustion gases are highly wavelength dependent. Better models for calculating the radiative properties of combustion gases are highly required in the modeling of large scale industrial combustion systems. With detailed knowledge of spectral radiative properties of gases, the modeling of combustion processes in the different applications can be more accurate. In order to propose a new method for effective non gray modeling of radiative heat transfer in combustion systems, different models for the spectral properties of gases including SNBM, EWBM, and WSGGM have been studied in this research. Using this detailed analysis of different approaches, the thesis presents new methods for gray and non gray radiative heat transfer modeling in homogeneous and inhomogeneous H2O–CO2 mixtures at atmospheric pressure. The proposed method is able to support the modeling of a wide range of combustion systems including the oxy-fired combustion scenario. The new methods are based on implementing some pre-obtained correlations for the total emissivity and band absorption coefficient of H2O–CO2 mixtures in different temperatures, gas compositions, and optical path lengths. They can be easily used within any commercial CFD software for radiative heat transfer modeling resulting in more accurate, simple, and fast calculations. The new methods were successfully used in CFD modeling by applying them to industrial scale backpass channel under oxy-fired conditions. The developed approaches are more accurate compared with other methods; moreover, they can provide complete explanation and detailed analysis of the radiation heat transfer in different systems under different combustion conditions. The methods were verified by applying them to some benchmarks, and they showed a good level of accuracy and computational speed compared to other methods. Furthermore, the implementation of the suggested banded approach in CFD software is very easy and straightforward.

Relieved after Doctor's Consultation? Primary Health Care Patients' Complaint-related Worries

Worry is one of the central factors in primary health care patients’ experience with their current complaint. Worry is associated with, e.g., patients’ expectations and the outcomes of doctor’s consultations. The aim of this study was to explore primary health care patients’ complaint-related worry and its changes, as well as contributing factors. Furthermore, the reasons behind patients’ pre-consultation worry and possible relief were examined. The study was conducted in a public primary health care centre in Forssa in Southern Finland. Patients, aged 18–39 years, with a current complaint were interviewed before and after a doctor’s consultation. The patients’ characteristics, perceptions of their complaint and their expectations and experiences concerning the consultation were obtained through interviews. In addition, two questionnaires were administered to measure general tendency to illness worry (IWS) and psychiatric symptoms (SCL-90). The patients’ ratings of the intensity of worry and the severity of their complaint were measured with a visual analogue scale (VAS 0–100). Changes in worry were measured by comparing pre- and post-consultation VAS ratings and asking the patients to compare their worry after the consultation with the worry they felt before it. In connection with these ratings the patients also gave reasons for their experiences in their own words. The patients’ doctors assessed the medical severity of the complaints and whether they had found a medical explanation for the complaints. Many patients were very worried before the consultation (65 % scored over 50 points on the VAS). Worry and severity ratings were associated with the duration and course of the complaint, with a general tendency to illness worry and hostility. On average, the patients were less worried after the consultation than before it. Persistent worry was associated with the patients’ uncertainty about their complaint, their perceiving it as severe, expectations for examinations and reporting symptoms of anxiety. Patients were most often worried about the nature of their complaint (e.g. duration or intensity), not knowing what was wrong, the possible harmful effects of the complaint on body functions, the complaint’s prognosis, e.g. will it get better, and their ability to function. Patients were relieved by getting an explanation or treatment or by having a positive view of the complaint’s prognosis. Patients who reported uncertainty (lack of an explanation, worry about the nature of the complaint) or worry about the complaint’s possible bodily harmfulness were relieved by getting an explanation, often accompanied with getting treatment. On the other hand, worries about the ability to function tended to persist. Doctors should bring up patients’ worries for discussion in order to be able to respond to them appropriately. Because it tends to persist, worry about the ability to function should be addressed. Uncertain patients with concerns about their complaint’s bodily harmfulness or psychological consequences need special attention from their doctor.

Determinants of credit risk in secured loans – Evidence from the auto loan industry

The purpose of this study is to examine attributes which have explanation power to the probability of default or serious overdue in secured auto loans. Another goal is to find out differences between defaulted loans and loans which have had payment difficulties but survived without defaulting. 19 independent variables used in this study reflect information available at the time of credit decision. These variables were tested with logistic regression and backward elimination procedure. The data includes 8931 auto loans from a Finnish finance company. 1118 of the contracts were taken by company customers and 7813 by private customers. 130 of the loans defaulted and 584 had serious payment problems but did not default. The maturities of those loans were from one month to 60 months and they have ended during year 2011. The LTV (loan-to-value) variable was ranked as the most significant explainer because of its strong positive relationship with probability of payment difficulties. Another important explainer in this study was the credit rating variable which got a negative relationship with payment problems. Also maturity and car age performed well having both a positive relationship with the probability of payment problems. When compared default and serious overdue situations, the most significant differences were found in the roles of LTV, Maturity and Gender variables.

Stop bugging me! : diversity in appearance of warning coloration

In nature, many animals use body coloration to communicate with each other. For example, colorations can be used as signals between individuals of the same species, but also to recognise individuals of other species, and if they may comprise a threat or not. Many animals use protective coloration to avoid predation. The two most common strategies of protective coloration are camouflage and aposematism. Camouflaged animals have coloration that minimises detection, usually by matching colours or structures in the background. Aposematic animals, on the other hand, signal to predators that they are defended. The defence can be physical structures, such as spikes and hairs, or chemical compounds that make the animal distasteful or even deadly toxic. In order for the warning signal to be effective, the predator has to recognise it as such. Studies have shown that birds for example, that are important visual predators on insects, learn to recognise and avoid unpalatable prey faster if they contrast the background or have large internal contrasts. Typical examples of aposematic species have conspicuous colours like yellow, orange or red, often in combination with black. My thesis focuses on the appearance and function of aposematic colour patterns. Even though researchers have studied aposematism for over a century, there is still a lot we do not know about the phenomenon. For example, as it is crucial that the predators recognise a warning signal, aposematic colorations should assumingly evolve homogeneously and be selected for maximal conspicuousness. Instead, there is an extensive variation of colours and patterns among warning colorations, and it is not uncommon to find typical cryptic colours, such as green and brown in aposematic colour patterns. One hypothesis to this variation is that an aposematic coloration does not have to be maximally signalling in order to be effective, instead it is sufficient to have distinct features that can be easily distinguished from edible prey. To be maximally conspicuous is one way to achieve this, but not the only way. Another hypothesis is that aposematic prey that do not exhibit maximal conspicuousness can exploit both camouflage and aposematism in a distance-dependent fashion, by being signalling when seen close up but camouflaged at a distance. Many prey animals also make use of both strategies by shifting colour at different ecological conditions such as seasonal variations, fluctuations in food resources or between life stages. Yet another explanation for the variation may be that prey animals are usually exposed to several predator species that vary in visual perception and tolerance towards various toxins. The aim with this thesis is, by studying their functions, to understand why aposematic warning signals vary in appearance, specifically in the level of conspicuousness, and if warning coloration can be combined with camouflage. In paper I, I investigated if the colour pattern of the aposematic larva of the Apollo butterfly (Parnassius apollo) can switch function with viewing distance, and be signalling at close range but camouflaged at a distance, by comparing detection time between different colour variants and distances. The results show that the natural coloration has a dual distance-dependent function. Moreover, the study shows that an aposematic coloration does not have to be selected for maximal conspicuousness. A prey animal can optimise its coloration primarily by avoiding detection, but also by investing in a secondary defence, which presence can be signalled if detected. In paper II, I studied how easily detected the coloration of the firebug (Pyrrhocoris apterus), a typical aposematic species, is at different distances against different natural backgrounds, by comparing detection time between different colour variants. Here, I found no distance-dependent switch in function. Instead, the results show that the coloration of the firebug is selected for maximal conspicuousness. One explanation for this is that the firebug is more mobile than the butterfly larva in study I, and movement is often incompatible with efficient camouflage. In paper III, I investigated if a seasonal related colour change in the chemically defended striated shieldbug (Graphosoma lineatum) is an adaptation to optimise a protective coloration by shifting from camouflage to aposematism between two seasons. The results confirm the hypothesis that the coloration expressed in the late summer has a camouflage function, blending in with the background. Further, I investigated if the internal pattern as such increased the effectiveness of the camouflage. Again, the results are in accordance with the hypothesis, as the patterned coloration was more difficult to detect than colorations lacking an internal pattern. This study shows how an aposematic species can optimise its defence by shifting from camouflage to aposematism, but in a different fashion than studied in paper I. The aim with study IV was to study the selection on aposematic signals by identifying characteristics that are common for colorations of aposematic species, and that distinguish them from colorations of other species. I compared contrast, pattern element size and colour proportion between a group of defended species and a group of undefended species. In contrast to my prediction, the results show no significant differences between the two groups in any of the analyses. One explanation for the non-significant results could be that there are no universal characteristics common for aposematic species. Instead, the selection pressures acting on defended species vary, and therefore affect their appearance differently. Another explanation is that all defended species may not have been selected for a conspicuous aposematic warning coloration. Taken together, my thesis shows that having a conspicuous warning coloration is not the only way to be aposematic. Also, aposematism and camouflage is not two mutually exclusive opposites, as there are prey species that exploit both strategies. It is also important to understand that prey animals are exposed to various selection pressures and trade-offs that affect their appearance, and determines what an optimal coloration is for each species or environment. In conclusion, I hold that the variation among warning colorations is larger and coloration properties that have been considered as archetypically aposematic may not be as widespread and representative as previously assumed.

Combination of pulsed corona discharge with TiO2 photocatalysis: verification of hypothesis

The oxidation potential of pulsed corona discharge concerning aqueous impurities is limited in respect to certain refractory compounds. This may be enhanced in combination of the discharge with catalysis/photocatalysis as developed in homogeneous gas-phase reactions. The objective of the work consists of testing the hypothesis of oxidation potential enhancement in combination of the discharge with TiO2 photocatalysis applied to aqueous solutions of refractory oxalate. Meglumine acridone acetate was included for meeting the practical needs. The experimental research was undertaken into oxidation of aqueous solutions under conditions of various target pollutant concentrations, pH and the pulse repetition rate with plain electrodes and the electrodes with TiO2 attached to their surface. The results showed no positive influence of the photocatalyst, the pollutants were oxidized with the rate identical within the accuracy of measurements. The possible explanation for the observed inefficiency may include low UV irradiance, screening effect of water and generally low oxidation rate in photocatalytic reactions. Further studies might include combination of electric discharge with ozone decomposition/radical formation catalysts.