Liiketoimintaprosessien mittaaminen ja mallintaminen

Tutkimuksessa tutkitaan mallintamista ja mittaamista osana liiketoimintaproses-sien parantamista, sekä näiden asioiden kuvaamista soveltuvalla työkalulla. Ensin esitetään teoreettinen viitekehys siihen, kuinka prosesseja voidaan mitata ja mal-lintaa. Sitten raportoidaan käytännössä suoritettu kehitystyö, jolle on määritetty lähtö- ja tavoitetila. Työn onnistumista mitataan johtajahaastatteluin ja saatuja tuloksia verrataan teoriaan. Tutkimuksessa yhdistettiin analyyttinen mallinrakennus, tieteellinen ongelman-ratkaisutoiminta sekä konsultointi tarkoituksena saada aikaan kohde organisaati-olle sopiva konstruktio esitettyyn ongelmaan. Johtajahaastattelut analysoitiin ja suoritettiin kvalitatiivinen tarveanalyysi. Haastatteluja täydennettiin muulla kerä-tyllä aineistolla ja analyysin tarkkuutta pyritään kasvattamaan eri lähdeaineistojen ristivertailuilla. Yrityksissä on niin liiketoiminnalle elintärkeitä ydinprosesseja kuin niitä tukevia tukiprosessejakin. Niiden toiminta perustuu ennalta suunniteltuihin ja uudelleen-käytettäviin menetelmiin. Prosessit tulee sopeuttaa yrityksen arkkitehtuuriin ja niitä on jatkuvasti kehitettävä. Kehittäminen voidaan toteuttaa suurilla kertamuu-toksilla, jatkuvalla laadun parantamisella tai niiden yhdistelmänä. Mallintamisella ja mittaamisella on tärkeä tehtävä liiketoimintaprosessien kehit-tämisessä. Niiden avulla voidaan helpottaa erityisesti prosessien suunnittelua luomalla konkreettisia malleja ja mittareita prosesseista. Toteutuksessa käytettiin prototyyppilähestymistapaa ja työn onnistumista arvioivat yhtiön johtajat. Tutki-muksen tuloksia ovat eri tason prosessimallit, joiden luomisessa käytettiin eri mallintamistekniikoita, sekä mittaristot mittaamaan yrityksen tuottavuutta ja te-hokkuutta.

Novel CO2 Regulated Proteins in Synechocystis PCC 6803

The large biodiversity of cyanobacteria together with the increasing genomics and proteomics metadata provide novel information for finding new commercially valuable metabolites. With the advent of global warming, there is growing interest in the processes that results in efficient CO2 capture through the use of photosynthetic microorganisms such as cyanobacteria. This requires a detailed knowledge of how cyanobacteria respond to the ambient CO2. My study was aimed at understanding the changes in the protein profile of the model organism, Synechocystis PCC 6803 towards the varying CO₂ level. In order to achieve this goal I have employed modern proteomics tools such as iTRAQ and DIGE, recombinant DNA techniques to construct different mutants in cyanobacteria and biophysical methods to study the photosynthetic properties. The proteomics study revealed several novel proteins, apart from the well characterized proteins involved in carbon concentrating mechanisms (CCMs), that were upregulated upon shift of the cells from high CO₂ concentration (3%) to that in air level (0.039%). The unknown proteins, Slr0006 and flavodiiron proteins (FDPs) Sll0217-Flv4 and Sll0219-Flv2, were selected for further characterization. Although slr0006 was substantially upregulated under C_i limiting conditions, inactivation of the gene did not result in any visual phenotype under various environmental conditions indicating that this protein is not essential for cell survival. However, quantitative proteomics showed the induction of novel plasmid and chromosome encoded proteins in deltaslr0006 under air level CO₂ conditions. The expression of the slr0006 gene was found to be strictly dependent on active photosynthetic electron transfer. Slr0006 contains conserved dsRNA binding domain that belongs to the Sua5/YrdC/YciO protein family. Structural modelling of Slr0006 showed an alpha/beta twisted open-sheet structure and a positively charged cavity, indicating a possible binding site for RNA. The 3D model and the co-localization of Slr0006 with ribosomal subunits suggest that it might play a role in translation or ribosome biogenesis. On the other hand, deletions in the sll0217-sll218- sll0219 operon resulted in enhanced photodamage of PSII and distorted energy transfer from phycobilisome (PBS) to PSII, suggesting a dynamic photoprotection role of the operon. Constructed homology models also suggest efficient electron transfer in heterodimeric Flv2/Flv4, apparently involved in PSII photoprotection. Both Slr0006 and FDPs exhibited several common features, including negative regulation by NdhR and ambiguous cellular localization when subjected to different concentrations of divalent ions. This strong association with the membranes remained undisturbed even in the presence of detergent or high salt. My finding brings ample information on three novel proteins and their functions towards carbon limitation. Nevertheless, many pathways and related proteins remain unexplored. The comprehensive understanding of the acclimation processes in cyanobacteria towards varying environmental CO₂ levels will help to uncover adaptive mechanisms in other organisms, including higher plants.

Yleislääkärin vastaanottotapahtuma - näkökulmia laatuun

Tutkimuksen tavoitteena oli tutkia yleislääkärin vastaanottotapahtuman laadun eri ulottuvuuksia, erityisesti lääkärin ja potilaan arvioita vastaanottotapahtuman laadusta, sekä verrata näitä arvioita keskenään. Lisäksi tarkoituksena oli tutkia palkkausjärjestelmän yhteyttä laatuun sekä löytää sopivia välineitä yleislääkärin vastaanottotapahtuman laadun arviointiin. Tutkimuksessa käytettiin triangulaatiota sekä materiaalien, tutkijoiden että menetelmien osalta. Materiaali koostui kyselylomakkeista (2191 vastaanottotapahtumaa, 2167 lääkärin lomaketta ja 1777 potilaan lomaketta), potilasasiakirjoista (n=175) ja vastaanottotapahtumien videoinneista (n=20). Analyysissä käytettiin sekä kvantitatiivisia että kvalitatiivisia menetelmiä. Laatu koostuu tässä tutkimuksessa tieteellisteknisestä/ammatillisesta osaamisesta, vuorovaikutustaidoista ja taloudellisesta laadusta. Kaikki osatekijät olivat kyselylomaketutkimuksen perusteella varsin hyviä, ja potilaat arvioivat laadun kaikki osatekijät paremmiksi kuin lääkärit. Potilaiden selviytyminen ja voimaantuminen vastaanottotapahtuman jälkeen oli parempaa, mikäli he pitivät vuorovaikutuksen laatua hyvänä ja lääkäriä omalääkärinään. Kyselylomaketutkimus antoi laadusta kuitenkin positiivisemman kuvan kuin tutkijoiden potilasasiakirjojen ja videointien avulla tekemät arviot. Potilasasiakirjat oli laadittu puutteellisesti ja potilasasiakirjajärjestelmät vaikuttivat postilaisasiakirjojen laatuun. Tutkijoiden arvioimana lääkäreiden vuorovaikutustaidot olivat keskimäärin tyydyttävät. Lääkärin virkaehtosopimus ei näyttänyt vaikuttavan potilaan kokemaan laatuun, mutta väestövastuulääkärit kokivat sekä oman työnsä ammatillisen laadun että vuorovaikutustaitonsa paremmaksi kuin muut lääkärit. Väestövastuuterveyskeskuksissa myös hoidon jatkuvuus ja potilaan valinnanvapaus näyttivät toteutuvan muita terveyskeskuksia paremmin. Yleislääkärin työn laadun arviointiin tarvitaan useita menetelmiä. Potilasasiakirjajärjestelmien tulisi olla helppokäyttöisiä, interaktiivisia ja tietoa automaattisesti kerääviä, jotta niistä saataisiin luotettavaa tietoa laadun arvioimiseksi. Lääkärin työn itsearviointia on edelleen tutkittava ja kehitettävä.

Business models for Finnish biobanks

This study concentrates on developing a suitable business model for Finnish biobanks, with particular emphasis on value creation to stakeholders. The sub-objective of this thesis are to map the commercial possibilities of biobanks and potential barriers for business development. The study approaches the subject from the biobanks’ as well as the stakeholders’ point of view, integrating their hopes and needs considering current and future co-operation into the findings. In 2013 the Biobank Act came into effect, after which six biobanks have been established and several other pending biobank projects are in process. There is relatively little research in regard to the commercial opportunities of this newcomer of the biomedical industry, and particularly in the Finnish markets. Therefore, the aim of this study is to partially fill the research gap of the commercial potential of biobanks and particularly outline the problematic elements in developing business. The theoretical framework consists of a few select theories, which depict business modeling and value creation of organizations. The theories are combined to form a synthesis, which best adapts to biobanks, and acts as a backbone for interviews. The empirical part of the study was conducted mainly by seven face-to-face interviews, and complemented by two phone interviews and an e-mail questionnaire with four responses. The findings consist mainly of the participants’ reflections on the potential products and services enabled by consumer genomics, as well as perceptions on different obstacles for biobanks’ business development. The nature of the study is tentative, as biobanks are relatively new organizations in Finland, and their operation models and activities are still molding. The aim is to bring to surface the hopes and concerns of biobanks’ representatives, as well as the representatives of stakeholders, in order to transparently discuss the current situation and suggestions for further development. The study concludes that in principle, the interviewees’ agree on the need for development in order not to waste the potential of biobanks; regardless, the participants emphasize different aspects and subsequently lean on differing methods.

Business models for Finnish biobanks

This study concentrates on developing a suitable business model for Finnish biobanks, with particular emphasis on value creation to stakeholders. The sub-objective of this thesis are to map the commercial possibilities of biobanks and potential barriers for business development. The study approaches the subject from the biobanks’ as well as the stakeholders’ point of view, integrating their hopes and needs considering current and future co-operation into the findings. In 2013 the Biobank Act came into effect, after which six biobanks have been established and several other pending biobank projects are in process. There is relatively little research in regard to the commercial opportunities of this newcomer of the biomedical industry, and particularly in the Finnish markets. Therefore, the aim of this study is to partially fill the research gap of the commercial potential of biobanks and particularly outline the problematic elements in developing business. The theoretical framework consists of a few select theories, which depict business modeling and value creation of organizations. The theories are combined to form a synthesis, which best adapts to biobanks, and acts as a backbone for interviews. The empirical part of the study was conducted mainly by seven face-to-face interviews, and complemented by two phone interviews and an e-mail questionnaire with four responses. The findings consist mainly of the participants’ reflections on the potential products and services enabled by consumer genomics, as well as perceptions on different obstacles for biobanks’ business development. The nature of the study is tentative, as biobanks are relatively new organizations in Finland, and their operation models and activities are still molding. The aim is to bring to surface the hopes and concerns of biobanks’ representatives, as well as the representatives of stakeholders, in order to transparently discuss the current situation and suggestions for further development. The study concludes that in principle, the interviewees’ agree on the need for development in order not to waste the potential of biobanks; regardless, the participants emphasize different aspects and subsequently lean on differing methods.

Consumer perceptions on a content-based digital service:the usage and service quality of Masennusinfo.fi

Kuluttajat käyttävät sisältöpohjaisia digitaalisia palveluita jatkuvasti saadakseen lisää tietoa terveydestään. Samalla he arvioivat käyttämiensä palveluiden laatua. Jotta yritykset voisivat suunnitella ja tarjota parhaita mahdollisia digitaalisia palveluita kuluttajille, yritysten tulisi tunnistaa ja analysoida kuluttajien kokemuksia ja käyttötarkoituksia heidän palveluissaan. Tämän tutkimuksen tarkoituksena on kuvailla kuluttajien näkemyksiä Masennusinfo.fi:stä, joka on sisältöpohjainen digitaalinen palvelu, ja joka tarjoaa käyttäjilleen tietoa masennuksesta. Päämääränä on selvittää, kuinka kuluttajat kokevat lääkeyrityksen tarjoaman palvelun laadun ja mihin tarkoituksiin sitä käytetään. Tutkimuksen tarkoitus voidaan jakaa kolmeen osa-ongelmaan: Mihin tarkoituksiin kuluttajat käyttävät sisältöpohjaisia digitaalisia palveluita? Miten kuluttajat kokevat näiden palveluiden laadun? Kuinka käyttötarkoitus ja koettu laatu eroavat eri käyttäjäryhmissä? Tutkimus toteutetaan web-pohjaisella kyselytutkimuksella. Mittarit tehdään teoreettisen viitekehyksen pohjalta, joka perustuu aikaisempaan tutkimukseen. Tutkimuksen empiirinen osuus suoritetaan pop-up tutkimuksella, joka sijoitetaan tutkittavalle sivustolle antaen näin kaikille palvelun käyttäjille mahdollisuuden vastata kyselyyn. Tulokset osoittavat, että palvelua käyttävät suurimmaksi osaksi naiset, suhteellisen nuoret 16−29- vuotiaat, tai yli keski-ikäiset 50−65-vuotiaat henkilöt, jotka ovat joko työssäkäyviä tai opiskelijoita ja korkeasti koulutettuja. Masennusinfo.fi nähdään laadukkaana palveluna kaikissa käyttäjäryhmissä sekä sen käytettävyyden että sisällön perusteella. Käyttötarkoituksetkin ovat jokseenkin samankaltaisia eri käyttäjäryhmissä. Yleensä palvelua käytetään tiedon hakemiseen sairauden alkuvaiheessa. Löydöksien perusteella esitetään, että palvelua muokataan vastaamaan yhä paremmin sen käyttötarkoituksia ja tyypillistä käyttäjäprofiilia. Koska muutamia pieniä eroja käyttäjäryhmien näkemyksissä havaittiin, palveluiden tuottaja päättää, minkä ryhmän mieltymyksiä se noudattaa.

Quality of the ryegrass and lettuce yields as affected by selenium fertilization

Selostus: Seleenilannoituksen vaikutus raiheinän ja salaatin laatuun

Improving Satellite Image Based Forest Inventory by Using A Priori Site Quality Information

Summary

Improvement of pyrolysis oil quality by scrubbing

Diplomityössä tutkittiin kuuman pyrolyysihöyryn puhdistamista haisevista ja kevyistä haihtuvista yhdisteistä. Työn kirjallisuusosassa selvitettiin pyrolyysiöljyn kannattavuutta uusiutuvana energialähteenä. Lisäksi eri pesurityyppejä tarkasteltiin ja ja vertailtiin. Työn kokeellisessa osassa käytettiin kahta erilaista koelaitteistoa. Tuotteen talteenotossa vertailtiin reaktorilämpötilan ja raaka-aineen kosteuden vaikutusta pyrolyysisaantoihin. Komponenttien talteenotossa tutkittiin epästabiilien ja pistävän hajuisten yhdisteiden poistamista kuumasta pyrolyysihöyrystä. Raaka-aineena käytettiin kuusen metsätäh-dehaketta, joka sisältää runsaasti neulasia ja kaarnaa. Kokeet toteutettiin lämpötila-alueella 460 - 520 °C. Koelaitteistot koostuivat kaasun (N2) syöttöjärjestelmään kytketystä kuumasta ja kyl-mästä puolesta. Tuotteen talteenotossa kuuma pyrolyysihöyry jäähdytettiin ja otettiin talteen. Komponenttien talteenotossa tuote kerättiin suodattimelle ja metyleeniklo-ridiloukkuun. Tuotteiden koostumukset analysoitiin kaasukromatokrafilla. Korkeimmat orgaaniset saannot saatiin 480 °C reaktorilämpötilalla ja 8-9 p-% raaka-ainekosteudella. Pyrolyysiveden määrä putosi raaka-aineen kosteutta nostettaessa. Eri reaktorilämpötiloilla ja raaka-ainekosteuksilla ei ollut vaikutusta hiiltosaantoihin. Kaasusaannot (pääosin CO2, CO ja hiilivedyt) olivat noin 10 p-%. Komponenttien talteenotossa suodatin tukkeutui matalissa (< 250 °C) lämpötiloissa. Suodattimelle jäänyt materiaali oli pääosin neulasista ja kaarnasta peräisin olevia uuteaineita (pääosin hartsi- rasvahappoja) ja sokereita. Korkeimmissa lämpötiloissa (> 250 °C) uuteaineet läpäisivät suodattimen paremmin. 250 ja 300 °C:n lämpötiloissa suuri määrä lyhytketjuisia helposti haihtuvia epästabiileja ja haisevia yhdisteitä (ketoneja, furaani- ja furfuraalijohdannaisia jne.) jäi metyleenikloridi- ja metanoliloukkuihin.

Performance benchmarking and incentive regulation – considerations of directing signals for electricity distribution companies

After the restructuring process of the power supply industry, which for instance in Finland took place in the mid-1990s, free competition was introduced for the production and sale of electricity. Nevertheless, natural monopolies are found to be the most efficient form of production in the transmission and distribution of electricity, and therefore such companies remained franchised monopolies. To prevent the misuse of the monopoly position and to guarantee the rights of the customers, regulation of these monopoly companies is required. One of the main objectives of the restructuring process has been to increase the cost efficiency of the industry. Simultaneously, demands for the service quality are increasing. Therefore, many regulatory frameworks are being, or have been, reshaped so that companies are provided with stronger incentives for efficiency and quality improvements. Performance benchmarking has in many cases a central role in the practical implementation of such incentive schemes. Economic regulation with performance benchmarking attached to it provides companies with directing signals that tend to affect their investment and maintenance strategies. Since the asset lifetimes in the electricity distribution are typically many decades, investment decisions have far-reaching technical and economic effects. This doctoral thesis addresses the directing signals of incentive regulation and performance benchmarking in the field of electricity distribution. The theory of efficiency measurement and the most common regulation models are presented. The chief contributions of this work are (1) a new kind of analysis of the regulatory framework, so that the actual directing signals of the regulation and benchmarking for the electricity distribution companies are evaluated, (2) developing the methodology and a software tool for analysing the directing signals of the regulation and benchmarking in the electricity distribution sector, and (3) analysing the real-life regulatory frameworks by the developed methodology and further develop regulation model from the viewpoint of the directing signals. The results of this study have played a key role in the development of the Finnish regulatory model.

Negative Regulation of Receptor Tyrosine Kinases by T-cell Protein Tyrosine Phosphatase

Protein tyrosine phosphorylation controls a wide array of cellular responses such as growth, migration, proliferation, differentiation, metabolism and cytoskeletal organisation. Tyrosine phosphorylation is a dynamic process involving the competing activities of protein tyrosine kinases and protein tyrosine phosphatases. The protein tyrosine kinases are further divided into non-receptor- and receptor tyrosine kinases. The latter are transmembrane glycoproteins activated by the binding of specific ligands, mostly growth factors, to their extracellular domain, transmitting different signals to the cell. Growth factor receptors such as the epidermal growth factor receptor, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β, belong to the receptor tyrosine kinases, the signalling of which is often disturbed in various diseases, including cancer. This has led to the development of receptor tyrosine kinase antagonists for use as anti-cancer drugs. As the receptor tyrosine kinases, also the protein tyrosine phosphatases can be divided into receptor- and non-receptor types. The protein tyrosine phosphatases have attained much less attention than the receptor tyrosine kinases partly because they were identified later. However, accumulating evidence shows that the protein tyrosine phosphatases have important roles as specific and active regulators of tyrosine phosphorylation in cells and of physiological processes. Consequently, the protein tyrosine phosphatases are receiving arising interest as novel drug targets. The aim of this work was to elucidate the negative regulation of receptor tyrosine kinases by one non-receptor protein tyrosine phosphatase, T-cell protein tyrosine phosphatase TCPTP. The results show that TCPTP activated by cell adhesion receptor integrin α1 functions as a negative regulator of the epidermal growth factor receptor. It was also found that TCPTP affects vascular endothelial growth factor receptor 2 signalling and angiogenesis. Lastly, a High-throughput screen with 64,280 compounds was performed to identify novel TCPTP activators, resulting in identification of one small molecule compound capable of exerting similar effects on TCPTP signalling as integrin α1. This compound is shown to downregulate signalling of epidermal growth factor receptor and platelet-derived growth factor receptor β, as well as to inhibit cell proliferation and angiogenesis. Our results suggest that a suitable small-molecule TCPTP activator could be utilized in the development of novel anti-cancer drugs.

Differential Regulation of c-FLIP Isoforms Through Post-translational Modifications

Cells are constantly responding to signals from the surrounding tissues and the environment. To dispose of infected and potentially dangerous cells, to ensure the optimal execution of developmental processes and to maintain tissue homeostasis, a multicellular organism needs to tightly control both the number and the quality of its cells. Apoptosis is a form of active cellular self-destruction that enables an organism to regulate its cell number by deleting damaged or potentially dangerous cells. Apoptosis can be induced by death ligands, which bind to death receptors on the cell surface. Ligation of the receptors leads to the formation of an intracellular death inducing signaling complex (DISC). One of the DISC components is caspase-8, a protease that triggers the caspase cascade and is thereby a key initiator of programmed cell death. The activation of caspase-8 is controlled by the cellular FLICE-inhibitory proteins (c-FLIPs). Consequently, sensitivity towards receptor-mediated apoptosis is determined by the amount of c-FLIP, and the c-FLIP levels are actively regulated for example during erythroid differentiation of K562 erythroleukemia cells and by hyperthermia in Jurkat leukemia cells. The aim of my thesis was to investigate how c-FLIP is regulated during these processes. We found that c-FLIP isoforms are short-lived proteins, although c-FLIPS had an even shorter half-life than c-FLIPL. In both experimental models, increased death receptor sensitivity correlated with induced ubiquitylation and consequent proteasomal degradation of c-FLIP. Furthermore, we elucidated how phosphorylation regulates the biological functions and the turnover of c-FLIP, thereby contributing to death receptor sensitivity. We mapped the first phosphorylation sites on c-FLIP and dissected how their phosphorylation affects c-FLIP. Moreover, we demonstrated that phosphorylation of serine 193, a phosphorylated residue common to all c-FLIPs, is primarily mediated by the classical PKC. Furthermore, we discovered a novel connection between the phosphorylation and ubiquitylation of c-FLIP: phosphorylation of S193 protects c-FLIP from ubiquitylation. Surprisingly, although all c-FLIP isoforms are phosphorylated on this conserved residue, the biological outcome is different for the long and short isoforms, since S193 specifically prolongs the half-lives of the short c-FLIP isoforms, but not c-FLIPL. To summarize, we show that c-FLIP proteins are modified by ubiquitylation and phosphorylation, and that the biological outcomes of these modifications are isoform-specifically determined.

Thylakoid Protein Phosphorylation in Regulation of Photosynthesis

Once the seed has germinated, the plant is forced to face all the environmental changes in its habitat. In order to survive, plants have evolved a number of different acclimation systems. The primary reaction behind plant growth and development is photosynthesis. Photosynthesis captures solar energy and converts it into chemical form. Photosynthesis in turn functions under the control of environmental cues, but is also affected by the growth, development, and metabolic state of a plant. The availability of solar energy fluctuates continuously, requiring non-stop adjustment of photosynthetic efficiency in order to maintain the balance between photosynthesis and the requirements and restrictions of plant metabolism. Tight regulation is required, not only to provide sufficient energy supply but also to prevent the damage caused by excess energy. The very first reaction of photosynthesis is splitting of water into the form of oxygen, hydrogen, and electrons. This most fundamental reaction of life is run by photosystem II (PSII), and the energy required for the reaction is collected by the light harvesting complex II (LHCII). Several proteins of the PSII-LHCII complex are reversibly phosphorylated according to the energy balance between photosynthesis and metabolism. Thylakoid protein phosphorylation has been under extensive investigation for over 30 years, yet the physiological role of phosphorylation remains elusive. Recently, the kinases behind the phosphorylation of PSII-LHCII proteins (STN7 and STN8) were identified and the knockout mutants of these kinases became available, providing powerful tools to elucidate the physiological role of PSII-LHCII phosphorylation. In my work I have used the stn7 and stn8 mutants in order to clarify the role of PSII-LHCII phosphorylation in regulation and protection of the photosynthetic machinery according to environmental cues. I show that STN7- dependent PSII-LHCII protein phosphorylation is required to balance the excitation energy distribution between PSII and PSI especially under low light intensities when the excitation energy transfer from LHC to PSII and PSI is efficient. This mechanism differs from traditional light quality-induced “state 1” – “state 2” transition and ensures fluent electron transfer from PSII to PSI under low light, yet having highest physiological relevance under fluctuating light intensity. STN8-dependent phosphorylation of PSII proteins, in turn, is required for fluent turn-over of photodamaged PSII complexes and has the highest importance upon prolonged exposure of the photosynthetic apparatus to excess light.

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.