The Regulation of Skeletal and Cardiac Muscle Blood Flow in Humans. Studies by positron emission tomography with special reference to exercise, adenosine and nitric oxide

Virtually every cell and organ in the human body is dependent on a proper oxygen supply. This is taken care of by the cardiovascular system that supplies tissues with oxygen precisely according to their metabolic needs. Physical exercise is one of the most demanding challenges the human circulatory system can face. During exercise skeletal muscle blood flow can easily increase some 20-fold and its proper distribution to and within muscles is of importance for optimal oxygen delivery. The local regulation of skeletal muscle blood flow during exercise remains little understood, but adenosine and nitric oxide may take part in this process. In addition to acute exercise, long-term vigorous physical conditioning also induces changes in the cardiovasculature, which leads to improved maximal physical performance. The changes are largely central, such as structural and functional changes in the heart. The function and reserve of the heart’s own vasculature can be studied by adenosine infusion, which according to animal studies evokes vasodilation via it’s a_2A receptors. This has, however, never been addressed in humans in vivo and also studies in endurance athletes have shown inconsistent results regarding the effects of sport training on myocardial blood flow. This study was performed on healthy young adults and endurance athletes and local skeletal and cardiac muscle blod flow was measured by positron emission tomography. In the heart, myocardial blood flow reserve and adenosine A_2A receptor density, and in skeletal muscle, oxygen extraction and consumption was also measured. The role of adenosine in the control of skeletal muscle blood flow during exercise, and its vasodilator effects, were addressed by infusing competitive inhibitors and adenosine into the femoral artery. The formation of skeletal muscle nitric oxide was also inhibited by a drug, with and without prostanoid blockade. As a result and conclusion, it can be said that skeletal muscle blood flow heterogeneity decreases with increasing exercise intensity most likely due to increased vascular unit recruitment, but exercise hyperemia is a very complex phenomenon that cannot be mimicked by pharmacological infusions, and no single regulator factor (e.g. adenosine or nitric oxide) accounts for a significant part of exercise-induced muscle hyperemia. However, in the present study it was observed for the first time in humans that nitric oxide is not only important regulator of the basal level of muscle blood flow, but also oxygen consumption, and together with prostanoids affects muscle blood flow and oxygen consumption during exercise. Finally, even vigorous endurance training does not seem to lead to supranormal myocardial blood flow reserve, and also other receptors than A_2A mediate the vasodilator effects of adenosine. In respect to cardiac work, atheletes heart seems to be luxuriously perfused at rest, which may result from reduced oxygen extraction or impaired efficiency due to pronouncedly enhanced myocardial mass developed to excel in strenuous exercise.

Kostean höyryn paisunnan erityispiirteet ydinvoimalaitosten turbiineissa

Diplomityössä käsitellään ydinvoimalaitoksen kostean höyryn alueella toimivien höyryturbiinien toiminnan erityispiirteitä. Tarkemmin työssä keskitytään Loviisan ydinvoimalaitoksen turbiiniprosessiin. Tavoitteena on selvittää veden tiivistymistä höyryvirrassa, sen erotusta höyrystä turbiineissa sekä määrittää laitokselle todellinen paisuntakäyrä. Työssä selvitettiin veden tiivistymistä höyryvirtaan kirjallisuuden ja prosessista saatujen tietojen perusteella. Lisäksi työssä tutustuttiin suurien nykyaikaisten kostean höyryn alueella toimivien turbiinien vedenerotukseen ja sen pohjalta arvioitiin Loviisan ydinvoimalaitoksen turbiinin kosteudenerotusta. Näiden tietojen avulla saatiin mallinnettua kostean höyryn paisuntakäyrä Loviisan ydinvoimalaitoksen turbiineille. Työssä perehdyttiin lisäksi ulosvirtauskanavan toimintaan. Diplomityön puitteissa ei perehdytty yksityiskohtaisesti veden tiivistymiseen höyryvirrassa, vaan aihe ansaitsee tarkempaa tutkimusta. Kosteuden erotustehokkuuden arviointi todellisessa prosessissa ilman mittauksista saatavaa tietoa on vaikeata, mutta toimenpiteisiin lisäinformaation saamiseksi Loviisan ydinvoimalaitoksen turbiiniprosessista on ryhdytty. Työssä tehtyjen selvitysten avulla saatiin arvokasta tietoa turbiinikoneikon toiminnasta ja sen tehokkuuden parantamisesta.

The intrinsic mechanisms of softwood fiber damage in brown stock fiber line unit operations Lappeenranta 2010

The effects of pulp processing on softwood fiber properties strongly influence the properties of wet and dry paper webs. Pulp strength delivery studies have provided observations that much of the strength potential of long fibered pulp is lost during brown stock fiber line operations where the pulp is merely washed and transferred to the subsequent processing stages. The objective of this work was to study the intrinsic mechanisms which maycause fiber damage in the different unit operations of modern softwood brown stock processing. The work was conducted by studying the effects of industrial machinery on pulp properties with some actions of unit operations simulated in laboratory scale devices under controlled conditions. An optical imaging system was created and used to study the orientation of fibers in the internal flows during pulp fluidization in mixers and the passage of fibers through the screen openings during screening. The qualitative changes in fibers were evaluated with existing and standardized techniques. The results showed that each process stage has its characteristic effects on fiber properties: Pulp washing and mat formation in displacement washers introduced fiber deformations especially if the fibers entering the stage were intact, but it did not decrease the pulp strength properties. However, storage chests and pulp transfer after displacement washers contributed to strength deterioration. Pulp screening proved to be quite gentle, having the potential of slightly evening out fiber deformations from very deformed pulps and vice versa inflicting a marginal increase in the deformation indices if the fibers were previously intact. Pulp mixing in fluidizing industrial mixers did not have detrimental effects on pulp strength and had the potential of slightly evening out the deformations, provided that the intensity of fluidization was high enough to allow fiber orientation with the flow and that the time of mixing was short. The chemical and mechanical actions of oxygen delignification had two distinct effects on pulp properties: chemical treatment clearly reduced pulp strength with and without mechanical treatment, and the mechanical actions of process machinery introduced more conformability to pulp fibers, but did not clearly contribute to a further decrease in pulp strength. The chemical composition of fibers entering the oxygen stage was also found to affect the susceptibility of fibers to damage during oxygen delignification. Fibers with the smallest content of xylan were found to be more prone to irreversibledeformations accompanied with a lower tensile strength of the pulp. Fibers poor in glucomannan exhibited a lower fiber strength while wet after oxygen delignification as compared to the reference pulp. Pulps with the smallest lignin content on the other hand exhibited improved strength properties as compared to the references.

Kenttätietojen hyödyntäminen taajuusmuuttajan luotettavuuden suunnittelussa

Taajuusmuuttaja on yhä yleisempi laite perinteisten oikosulkumoottoreiden nopeuden säädössä, niin teollisuudessa kuin muilla käyttökohteissa. Ensimmäiset laitetyypit olivat mekaanisesti suurikokoisia ja vaativat laitteen tekniseltä tuelta ja kunnossapidolta hyvää teknistä perehtyneisyyttä laitteisiin. Teknologian kehittymisen myötä laitteiden teho/kokosuhde on pienentynyt ja tarjolla on useita eri sovelluskohteisiin suoraan soveltuvia taajuusmuuttajia varustettuna helppokäyttöisillä ja kaupallisilla käyttöliittymillä. Laitteen elinkaaren aikainen luotettavuusjohtaminen edellyttää valmistajalta varsinaisen laitesuunnittelun lisäksi tarkoituksenmukaisia testausmenetelmiä ja kokemusperäistä luotettavuustietoa myös asennetusta laitekannasta. Työssä on käyty taajuusmuuttajan suunnittelun kannalta läpi luotettavuuden käsitteistö sekä yleisimpiä luotettavuusmenetelmiä. Luotettavuusnäkökohtia verrataan asennetusta laitekannasta saatuihin kokemuksiin laitteen valmistajan ja tuotetuen kannalta. Työssä on esitetty luokittelun perusteita ja menetelmät, miten käytön aikana voidaan arvioida laitteen teknistä tilaa sekä huomioida se kunnossapidon suunnittelussa. Johtopäätöksenä huomataan, että asennuspaikka ja käyttösovellus määrittävät taajuusmuuttajan käytettävyyden. Kenttätietoja voidaan hyödyntää paikallisen kunnossapidon kannalta kunnossapidon ja investointien suunnittelussa. Toisaalta valmistajan tuotekehitys saa asennetuista laitteista kokemuksia seuraavan sukupolven tyypin suunnittelun perustaksi. Tekniikan voimakkaan kehittymisen seurauksena uusien taajuusmuuttajatyyppien valmistus kestää yhä lyhyemmän ajanjakson, jolloin asennetusta laitekannasta saatu kenttäkokemus on arvokasta tietoa laitevalmistajalle. Yhteenvetona valmistajan laiterekistereitä voidaan kehittää siten, että niihin on tallennettavissa laitekartoitusten perusteella kerättyä informaatiota, jota niin valmistajan myynti, tuotetuki kuin laitesuunnittelu voi omassa toiminnassaan hyödyntää.

Surgically-treated Hip Fracture in older People. With Special Emphasis on Mortality Analysis

Hip fractures are associated with significant morbidity and mortality. Cervical and trochanteric fractures have a different morphometry, surgical treatment, and outcome. Polypharmacy, common in older people, is associated with increased mortality. The risk factors for mortality can be identified based on cause-of-death analysis. In this population-based study, 461 older, surgically in 1999-2000 treated hip fracture patients were enrolled. Incidence, morphometry, medication, mortality, and cause-of-death were analysed. Hip fractures were most commonly sustained by women, occurred mostly indoors, and often in institutions. One in four patients had sustained a previous fracture. Routine clinical radiographs revealed no differences in the hip geometry between hip fracture types. Age-adjusted mortality was higher in men than in women during the follow-up. Chronic lung disease and male sex were predictors of mortality after cervical fracture. In men, potent anticholinergics were associated with excess age-adjusted mortality. Men were more likely to die from circulatory disease and dementia after hip fracture than women. Mortality after hip fracture was 3-fold higher than that of the general population, including every cause-of-death class. Fracture prevention in institutions and homes, indoor safety measures, and treatment of chronic lung diseases should be encouraged. Hip morphometry analyses require more accurate measures than that provided by routine radiographs. Careful use of potent anticholinergics may reduce mortality. Compared to the general population, excess mortality after hip fracture was evident up to 9 years after hip fracture. Cause-of-death analysis indicates that all major comorbidities require optimal treatment after hip fracture surgery.

Pienen ICT-yrityksen kansainvälistymissuunnitelma

Pienen ICT-yrityksen kansainvälistymisoperaatioita suunnitellessa tulee huomioida käytössä olevat resurssit, kansainvälisten toimintojen aloittamiseen kuluva aika sekä sitoutumishalukkuus suhteutettuna riskeihin. Tämän diplomityön lähtökohtana oli määrittää kohdeyritykselle, ZapMeet Companylle, suunnitelma kansainvälistymisen aloittamiseksi. Tutkimuksessa selvitetään pk-yrityksille tyypillisiä kansainvälistymispolkuja, kansainvälistymisen operaatiomuotoja ja kohdemarkkinavalintoja sekä näihin vaikuttavia kriteerejä. Tutkimuksen ensimmäisessä vaiheessa analysoitiin ZapMeet Companyn nykytilanne ja selvitettiin kansainvälistymiseen vaadittavia toimenpiteitä. Tutkimuksen toisessa vaiheessa pureuduttiin kulttuurin ja operaatiomuotojen erityispiirteisiin valikoiduilla markkinoilla. Teoriakehys, markkinoiden erityispiirteet sekä asiantuntijoiden kommentit ja yrityksen resurssit huomioiden diplomityön perusteella muodostettiin suosituksia operaatiomuodon sekä ensimmäisen kohdemarkkinan valintaan. Lisäksi työssä otetaan kantaa vastuun jakoon, tuotteen sopeuttamiseen sekä yhteistyökumppanin valintaan.

Toimittajavarastointi teollisuusyrityksen kilpailuetuna sekä sen aiheuttamien kustannusten tarkastelu

Työn tavoitteena on tutkia toimittajavarastointia sekä siitä aiheutuvia kus-tannuksia. Työssä perehdytään tarkemmin toimitusketjun eri osapuolien väliseen yhteistyömalliin sekä tarkastellaan varastoinnin aiheuttamia kus-tannuksia yleisellä tasolla, sekä toimittajavarastointimallin mukanaan tuo-mien erillisten kustannuserien käsittelyä. Lisäksi tutkitaan, miten toimitta-javarastointimalli tuo lisähyötyä toimittajan toimintaan kilpailijoihin nähden. Tutkimus sisältää teoriaosuuden ja empiirisen osuuden, joissa esitellään aiheeseen liittyviä lainalaisuuksia ja erään teollisuusyrityksen toimittajavarastointia kahden esimerkkiasiakkaan kesken, sekä näiden asiakkaiden toimittajavarastoinnista esimerkkiyritykselle aiheutuvia kustannuksia. Teoriaosuudessa selvitetään toimittajavarastointiin liittyviä teoreettisia lähtökohtia ja sen vaikutuksia yritysten toimintaan. Kyseessä on kvalitatiivinen tapaustutkimus, jossa empiirinen aineisto ke-rättiin havainnoinnin, haastattelujen ja valmiiden dokumenttien perusteella sekä esimerkkiyrityksen tietokannoista. Teoriaosuuden lähteenä käytettiin aikaisempaa alan kirjallisuutta sekä artikkeleita. Tuloksena esitetään kustannusten laskentamalli, jonka avulla voidaan selvittää toimittajavarastoinnista aiheutuvat kustannukset ja niiden ositusperusteet.

Fibroblast Growth Factor 8 and its Receptors in The Growth and Angiogenesis of Experimental Breast Cancer . With Special Reference to Thrombospondin-1 as a Novel Target Gene for FGF-8

The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.

Bonding of Composite Resin to Alumina and Zirconia Ceramics with Special Emphasis on Surface Conditioning and Use of Coupling Agents

Dental oxide ceramics have been inspired by their biocompability and mechanical properties which have made durable all-ceramic structures possible. Clinical longevity of the prosthetic structures is dependent on effective bonding with luting cements. As the initial shear bond strength values can be comparable with several materials and procedures, long-term durability is affected by ageing. Aims of the current study were: to measure the shear bond strength of resin composite-to-ceramics and to evaluate the longevity of the bond; to analyze factors affecting the bond, with special emphasis on: the form of silicatization of the ceramic surface; form of silanization; type of resin primer and the effect of the type of the resin composite luting cement; the effect of ageing in water was studied regarding its effect to the endurance of the bond. Ceramic substrates were alumina and yttrium stabilized zirconia. Ceramic conditioning methods included tribochemical silicatization and use of two silane couplings agents. A commercial silane primer was used as a control silane. Various combinations of conditioning methods, primers and resin cements were tested. Bond strengths were measured by shear bond strength method. The longevity of the bond was generally studied by thermocycling the materials in water. Additionally, in one of the studies thermal cycling was compared with long-term water storaging. Results were analysed statistically with ANOVA and Weibull analysis. Tribochemical treatment utilizing air pressure of 150 kPa resulted shear bond strengths of 11.2 MPa to 18.4 MPa and air pressure of 450 kPa 18.2 MPa to 30.5 MPa, respectively. Thermocycling of 8000 cycles or four years water storaging both decreased shear bond strength values to a range of 3.8 MPa to 7.2 MPa whereas initial situation varied from 16.8. Mpa to 23.0 MPa. The silane used in studies had no statistical significance. The use of primers without 10-MDP resulted spontaneous debonding during thermocycling or shear bond strengths below 5 MPa. As conclusion, the results showed superior long-term bonding with primers containing 10-MDP. Silicatization with silanizing showed improved initial shear bond strength values which considerably decreased with ageing in water. Thermal cycling and water storing for up to four years played the major role in reduction of bond strength, which could be due to thermal fatigue of the bonding interface and hydrolytic degradation of the silane coupled interface.

Quasiconformal mappings and inequalities involving special functions

This PhD thesis in Mathematics belongs to the field of Geometric Function Theory. The thesis consists of four original papers. The topic studied deals with quasiconformal mappings and their distortion theory in Euclidean n-dimensional spaces. This theory has its roots in the pioneering papers of F. W. Gehring and J. Väisälä published in the early 1960’s and it has been studied by many mathematicians thereafter. In the first paper we refine the known bounds for the so-called Mori constant and also estimate the distortion in the hyperbolic metric. The second paper deals with radial functions which are simple examples of quasiconformal mappings. These radial functions lead us to the study of the so-called p-angular distance which has been studied recently e.g. by L. Maligranda and S. Dragomir. In the third paper we study a class of functions of a real variable studied by P. Lindqvist in an influential paper. This leads one to study parametrized analogues of classical trigonometric and hyperbolic functions which for the parameter value p = 2 coincide with the classical functions. Gaussian hypergeometric functions have an important role in the study of these special functions. Several new inequalities and identities involving p-analogues of these functions are also given. In the fourth paper we study the generalized complete elliptic integrals, modular functions and some related functions. We find the upper and lower bounds of these functions, and those bounds are given in a simple form. This theory has a long history which goes back two centuries and includes names such as A. M. Legendre, C. Jacobi, C. F. Gauss. Modular functions also occur in the study of quasiconformal mappings. Conformal invariants, such as the modulus of a curve family, are often applied in quasiconformal mapping theory. The invariants can be sometimes expressed in terms of special conformal mappings. This fact explains why special functions often occur in this theory.

Siirtymätalouksien tutkimuslaitoksen (BOFIT) kokoelma

Suomen Pankin kirjastolla on erilliskokoelma Siirtymätalouksien tutkimuslaitoksessa, BOFITissa. Kokoelma on painottunut siirtymätalouksia käsittelevään tieteelliseen kirjallisuuteen, tilasto- ja kausijulkaisuihin. Kokoelmaa on kartutettu 1980-luvulta lähtien ja siihen sisältyy merkittävä määrä nimekkeitä, joita ei ole hankittu muihin suomalaisiin kirjastoihin. Kokoelmaa on rajattu sekä aihepiireiltään että maantieteellisesti kulloistenkin tutkimuspainopisteiden mukaisesti. Kokoelman keskeinen aihealue on makrotalous ja erityisinä painopisteinä ovat rahatalous, talouspolitiikka ja talousuudistukset. Paljon kirjallisuutta löytyy myös raha- ja valuuttapolitiikasta, pankkitoiminnasta ja kansainvälisistä taloussuhteista. Maantieteellisinä painopisteinä ovat tällä hetkellä erityisesti Venäjä ja Kiina. Vanhempaa aineistoa löytyy myös Baltian sekä Itä-Euroopan maista, Neuvostoliitosta sekä Suomen idänkaupasta. Kirjakokoelma sisältää n. 5300 nimekettä, lehtikokoelma n. 150 nimekettä. Artikkeliviitteitä löytyy n. 2300 vuodesta 1990 lähtien. Kokoelma sisältää tiedot myös kaikesta BOFITin omasta julkaisutuotannosta. Suurin osa kokoelmasta on englanninkielistä.

A quantitative view on fuzzy numbers

Since its introduction, fuzzy set theory has become a useful tool in the mathematical modelling of problems in Operations Research and many other fields. The number of applications is growing continuously. In this thesis we investigate a special type of fuzzy set, namely fuzzy numbers. Fuzzy numbers (which will be considered in the thesis as possibility distributions) have been widely used in quantitative analysis in recent decades. In this work two measures of interactivity are defined for fuzzy numbers, the possibilistic correlation and correlation ratio. We focus on both the theoretical and practical applications of these new indices. The approach is based on the level-sets of the fuzzy numbers and on the concept of the joint distribution of marginal possibility distributions. The measures possess similar properties to the corresponding probabilistic correlation and correlation ratio. The connections to real life decision making problems are emphasized focusing on the financial applications. We extend the definitions of possibilistic mean value, variance, covariance and correlation to quasi fuzzy numbers and prove necessary and sufficient conditions for the finiteness of possibilistic mean value and variance. The connection between the concepts of probabilistic and possibilistic correlation is investigated using an exponential distribution. The use of fuzzy numbers in practical applications is demonstrated by the Fuzzy Pay-Off method. This model for real option valuation is based on findings from earlier real option valuation models. We illustrate the use of number of different types of fuzzy numbers and mean value concepts with the method and provide a real life application.

Possibilities and challenges of longitudinal studies in operations management

Longitudinal studies are quite rare in the area of Operations Management. One reason might be the time needed to conduct such studies, and then the lack of experience and real-life examples and results. The aim of the thesis is to examine longitudinal studies in the area of OM and the possible advantages, challenges and pitfalls of such studies. A longitudinal benchmarking study, Made in Finland, was analyzed in terms of the study methodology and its outcomes. The timeline of this longitudinal study is interesting. The first study was made in 1993, the second in 2004 and the third in 2010. Between these studies some major changes occurred in the Finnish business environment. Between the first and second studies, Finland joined the ETA and the EU, and globalization started with the rise of the Internet era, while between the second and third studies financial turmoil started in 2007. The sample and cases used in this study were originally 23 manufacturing sites in Finland. These sites were interviewed in 1993, in 2004 and 2010. One important and interesting aspect is that all the original sites participated in 2004, and 19 sites were still able to participate in 2010. Four sites had been closed and/or moved abroad. All of this gave a good opportunity to study the changes that occurred in the Finnish manufacturing sites and their environment, and how they reacted to these changes, and the effects on their performance. It is very seldom, if ever, that the same manufacturing sites have been studied in a longitudinal setting by using three data points. The results of this study are thus unique, and the experience gained is valuable for practitioners.