The Cellular Oxygen Sensor PHD2 in Cancer Growth

Adequate supply of oxygen is essential for the survival of multicellular organisms. However, in several conditions the supply of oxygen can be disturbed and the tissue oxygenation is compromised. This condition is termed hypoxia. Oxygen homeostasis is maintained by the regulation of both the use and delivery of oxygen through complex, sensitive and cell-type specific transcriptional responses to hypoxia. This is mainly achieved by one master regulator, a transcription factor called hypoxiainducible factor 1 (HIF-1). The amount of HIF-1 is under tight oxygen-dependent control by a family of oxygen-dependent prolyl hydroxylase domain proteins (PHDs) that function as the cellular oxygen sensors. Three family members (PHD1-3) are known to regulate HIF of which the PHD2 isoform is thought to be the main regulator of HIF-1. The supply of oxygen can be disturbed in pathophysiological conditions, such as ischemic disorders and cancer. Cancer cells in the hypoxic parts of the tumors exploit the ability of HIF-1 to turn on the mechanisms for their survival, resistance to treatment, and escape from the oxygen- and nutrient-deprived environment. In this study, the expression and regulation of PHD2 were studied in normal and cancerous tissues, and its significance in tumor growth. The results show that the expression of PHD2 is induced in hypoxic cells. It is overexpressed in head and neck squamous cell carcinomas and colon adenocarcinomas. Although PHD2 normally resides in the cytoplasm, nuclear translocation of PHD2 was also seen in a subset of tumor cells. Together with the overexpression, the nuclear localization correlated with the aggressiveness of the tumors. The nuclear localization of PHD2 caused an increase in the anchorage-independent growth of cancer cells. This study provides information on the role of PHD2, the main regulator of HIF expression, in cancer progression. This knowledge may prove to be valuable in targeting the HIF pathway in cancer treatment.

Teollisuuden jäähdytysjärjestelmät. Case: Kaasunerotuslaitteiston evaluointi

Teollisuuden jäähdytysjärjestelmiä tarvitaan prosessien lämpötilan ja paineen hal-litsemiseen. Vesi on käytetyin lämmönsiirtoaine hyvän saatavuutensa, halvan hin-nan ja korkean lämmönsiirtokyvyn ansiosta. Jäähdytysjärjestelmät jaetaan kolmeen päätyyppiin, joita ovat läpivirtausjäähdytys, suljettu ja avoin kiertojäähdytys. Kullakin järjestelmätyypillä on tyypilliset alatyyppinsä. Avoimella kiertojär-jestelmällä on eniten alatyyppejä, joista yleisin on jäähdytystorni. Jäähdytystorneja on kolmea tyyppiä: märkä-, kuiva ja hybriditorni. Kullakin järjestelmätyypillä on ominaiset piirteensä käyttökohteiden, ympäristövaikutusten, ohjattavuuden, investointi- ja käyttökulujen suhteen, joita tässä työssä esitellään. Työssä tutkitaan teollisuuden jäähdytysjärjestelmien esittelyn lisäksi erään ali-painekaasunpoistimen soveltuvuutta suljetun kiertojäähdytysjärjestelmän kaasun-poistoon. Suljettuun kiertojäähdytysjärjestelmään jää ilmaa täyttövaiheessa ja kul-keutuu liuenneena käytettävän jäähdytysveden mukana. Muodostuva ylikylläinen seos synnyttää veden sekaan ilmakuplia, jotka aiheuttavat korroosiota kemiallisesti ja kuluttamalla. Lisäksi kaasukuplat vievät tilavuutta nesteeltä. Tämä pienentää järjestelmän jäähdytystehoa merkittävästi, koska kaasun lämmönsiirtokyky verrat-tuna veden lämmönsiirtokykyyn on pieni. Työssä esitellään myös muita mahdolli-sia suljetun järjestelmän kaasulähteitä ja niiden aiheuttamia ongelmia. Alipainekaasunpoistimen kaasunerotustehokkuutta mitattiin jäähdytysvesinäyttei-den selkeytymisnopeudella ja lämmönsiirtimien tehon paranemisella. Kahden viikon tarkastelujaksolla selkeytymisajat paranivat 36–60 % eri mittauspaikoissa ja lämmönsiirtimien tehot paranivat 6–29 %. Järjestelmään kuitenkin jäi merkittävä määrä kaasua, vaikka laitteen käyttöä jatkettiin tarkastelujakson jälkeen, joten tavoitteisiin ei päästy. Tutkitun alipainekaasunpoistolaitteen ei todettu soveltuvan tehdasympäristöön kestämättömyyden, hankalakäyttöisyyden ja tehottomuuden takia. Tulokset kuitenkin osoittavat, että kaasunerotuksella on merkittävä vaikutus suljetun jäähdytysjärjestelmän toimivuuteen ja saavutettavaan jäähdytystehoon.

Suljetun jäähdytysvesiverkon mallinnus

Työssä selvitettiin Neste Oil Porvoon jalostamon tuotantolinja 2 jäähdytysvesiverkon tilaa. Jäähdytysvesiverkon hydraulinen malli päivitettiin ja verifioitiin painemittauksin. Mallia tarkennettiin säätöventtiilien mallinnuksen sekä virhelähteiden tarkastelun perusteella havaituin muutoksin. Mallin verifioinnissa havaittiin huomattavia eroja mallin ja mitattujen paineiden välillä. Tämä johti mallin tarkempaan tarkasteluun, sekä virhelähteiden ja niiden vaikutusten selvittämiseen. Putkivarusteiden mallinnusmenetelmiä, sekä mallinnusperiaatteita vertailtiin keskenään. Koska jäähdytysveden kokonaiskierto oli riittämätön, tarkasteltiin kolmea vaihtoehtoa riittävän kiertovesimäärän aikaansaamiseksi. Nykyisten kiertovesipumppujen rinnanoperointi, sekä riittävän suureksi skaalatun pumpun käyttö simuloitiin. Kolmantena tapauksena arvioitiin lämmönvaihdinkohtaisen kuristussuunnitelman vaikutus putkiston painehäviöön, sekä putkistolle sopiva kiertovesipumppu. Vaihtoehdoille laskettiin suuntaa-antavat investointi- ja käyttökustannukset. Tarkastelun perusteella riittävän suureksi skaalattu pumppu todettiin kannattavimmaksi pienen hintaeron, sekä luotettavamman jäähdytysvesikierron käyttövarmuuden vuoksi. Työssä onnistuttiin tuottamaan yleispätevää tietoa suljetun jäähdytysvesiverkon hydrauliseen mallinnukseen vaikuttavista tekijöistä, sekä niiden vaikutuksesta mallin tarkkuuteen. Selvityksen perusteella tarkasteltua mallia saatiin tarkemmaksi.

Potential of the Osteoclast’s Proton Pump as a Drug Target in Osteoporosis

Decreasing bone mass during aging predisposes to fractures and it is estimated that every second woman and one in five men will suffer osteoporotic fractures during their lifetime. Bone is an adaptive tissue undergoing continuous remodeling in response to physical and metabolic stimuli. Bone mass decreases through a net negative balance in the bone remodeling process of bone, in which the new bone incompletely replaces the resorbed bone mass. Bone resorption is carried out by the osteoclasts; the bone mineral is solubilized by acidification and the organic matrix is subsequently degraded by proteases. Several classes of drugs are available for prevention of osteoporotic fractures. They act by different mechanisms to increase bone mass, and some of them act mainly as antiresorptives by inhibition of osteoclast formation or their function. Optimally, a drug should act selectively on a specific process, since other processes affected usually result in adverse effects. The purpose of this study was to evaluate whether the osteoclastic vacuolar adenosine trisphosphatases (V-ATPase), which drives the solubilization of bone mineral, can be selectively inhibited despite its ubiquitous cellular functions. The V-ATPase is a multimeric protein composed of 13 subunits of which six possesses two or more isoforms. Selectivity for the osteoclastic V-ATPase could be provided if it has some structural uniqueness, such as a unique isoform combination. The a3 isoform of the 116kDa subunit is inevitable for bone resorption; however, it is also present in, and mainly limited to, the lysosomes of other cells. No evidence of a structural uniqueness of the osteoclastic V-ATPase compared to the lysosomal V-ATPase was found, although this can not yet be excluded. Thus, an inhibitor selective for the a3 isoform would target the lysosomal V-ATPase as well. However, the results suggest that selectivity for bone resorption over lysosomal function can be obtained by two other mechanisms, suggesting that isoform a3 is a valid target. The first is differential compensation; bone resorption depends on the high level of a3 expression, and is not compensated for by other isoforms, while the lower level of a3 in lysosomes of other cells may be partly compensated for. The second mechanism is because the bone resorption process itself is fundamentally different from lysosomal acidification because of the chemistry of bone dissolution and the anatomy of the resorbing osteoclast. By this mechanism, full inhibition of bone resorption is obtained with more than tenfold lower inhibitor concentration than those needed to fully inhibit lysosomal acidification. The two mechanisms are additive. Based on the results, we suggest that bone resorption can be selectively inhibited if VATPase inhibitors that are sufficiently selective for the a3 isoform over the other isoforms are developed.

Laskentasovelluksen kehittäminen modulaariselle vesiputkikattilalle

Modulaarisella vesiputkikattilalla tarkoitetaan täysin konepajalla valmistettavissa olevaa kattilaa, joka voidaan kuljettaa yhtenä tai muutamana suurena moduulina työmaalle. Tässä diplomityössä käsiteltiin modulaarisen vesiputkikattilan laskentasovelluksen ke-hittämistä KPA Unicon Oy:lle. Työn tavoitteena oli tarkastella modulaarisen vesiputkikattilan lämpöteknistä mitoitusta ja suunnittelua sekä kehittää laskentasovellus, jonka avulla voidaan arvioida kattilan mittoja ja painoa. Laskentasovellus laadittiin Microsoftin Excel-alustalle, josta se on myöhemmin mahdollista siirtää muille ohjelma-alustoille. Laskentasovelluksessa hyödynnetään lämmönsiirron ja virtaustekniikan laskentayhtälöitä sekä -menetelmiä. Sovellukseen valitut laskentayhtälöt sekä -menetelmät ovat yleisesti hyväksyttyjä ja käytännössä testattuja. Diplomityön tuloksena valmistui laskentasovellus, joka kykenee modulaarisen vesiputkikattilan lämpötekniseen mitoittamiseen. Sovelluksen avulla voidaan mitoittaa kattilan tulipesä, tulistimet, höyrystinpinnat sekä ekonomaiseri. Laskentasovellusta on tarkoitus hyödyntää yrityksen tarjousvaiheen projekteissa sekä mahdollisesti kattiloiden esisuunnittelussa. Laskentasovelluksen laatimista varten ei ollut mahdollista hyödyntää toiminnassa olevien kattiloiden prosessitietoja, koska ensimmäiset tämän tyyppiset kattilat ovat asenteilla. Sen sijaan sovelluksen antamia laskentatuloksia verrattiin toisen mitoitusohjelman antamiin tuloksiin, joiden perusteella laskentasovelluksen voidaan olettaa antavan oikeita tuloksia.

Electroactive ion exchange membranes based on conducting polymers

Ion exchange membranes are indispensable for the separation of ionic species. They can discriminate between anions and cations depending on the type of fixed ionic group present in the membrane. These conventional ion exchange membranes (CIX) have exceptional ionic conductivity, which is advantageous in various electromembrane separation processes such as electrodialysis, electrodeionisation and electrochemical ion exchange. The main disadvantage of CIX membranes is their high electrical resistance owing to the fact that the membranes are electronically non conductive. An alternative can be electroactive ion exchange membranes, which are ionically and electronically conducting. Polypyrrole (PPy) is a type of electroactive ion exchange material as well as a commonly known conducting polymer. When PPy membranes are repeatedly reduced and oxidised, ions are pumped through the membrane. The main aim of this thesis was to develop electroactive cation transport membranes based on PPy for the selective transport of divalent cations. Membranes developed composed of PPy films deposited on commercially available support materials. To carry out this study, cation exchange membranes based on PPy doped with immobile anions were prepared. Two types of dopant anions known to interact with divalent metal ions were considered, namely 4-sulphonic calix[6]arene (C6S) and carboxylated multiwalled carbon nanotubes (CNT). The transport of ions across membranes containing PPy doped with polystyrene sulphonate (PSS) and PPy doped with para-toluene sulphonate (pTS) was also studied in order to understand the nature of ion transport and permeability across PPy(CNT) and PPy(C6S) membranes. In the course of these studies, membrane characterisation was performed using electrochemical quartz crystal microbalance (EQCM) and scanning electron microscopy (SEM). Permeability of the membranes towards divalent cations was explored using a two compartment transport cell. EQCM results demonstrated that the ion exchange behaviour of polypyrrole is dependent on a number of factors including the type of dopant anion present, the type of ions present in the surrounding medium, the scan rate used during the experiment and the previous history of the polymer film. The morphology of PPy films was found to change when the dopant anion was varied and even when the thickness of the film was altered in some cases. In nearly all cases the permeability of the membranes towards metal ions followed the order K+ > Ca2+ > Mn2+. The one exception was PPy(C6S), for which the permeability followed the order Ca2+ ≥ K+ > Mn2+ > Co2+ > Cr3+. The above permeability sequences show a strong dependence on the size of the metal ions with metal ions having the smallest hydrated radii exhibiting the highest flux. Another factor that affected the permeability towards metal ions was the thickness of the PPy films. Films with the least thickness showed higher metal ion fluxes. Electrochemical control over ion transport across PPy(CNT) membrane was obtained when films composed of the latter were deposited on track-etched Nucleopore® membranes as support material. In contrast, the flux of ions across the same film was concentration gradient dependent when the polymer was deposited on polyvinylidene difluoride membranes as support material. However, electrochemical control over metal ion transport was achieved with a bilayer type of PPy film consisting of PPy(pTS)/PPy(CNT), irrespective of the type of support material. In the course of studying macroscopic charge balance during transport experiments performed using a two compartment transport cell, it was observed that PPy films were non-permselective. A clear correlation between the change in pH in the receiving solution and the ions transported across the membrane was observed. A decrease in solution pH was detected when the polymer membrane acted primarily as an anion exchanger, while an increase in pH occurred when it functioned as a cation exchanger. When there was an approximately equal flux of anions and cations across the polymer membrane, the pH in the receiving solution was in the range 6 - 8. These observations suggest that macroscopic charge balance during the transport of cations and anions across polypyrrole membranes was maintained by introduction of anions (OH-) and cations (H+) produced via electrolysis of water.

Novel Functions of ErbB4 and NRG-1 in Development and Cancer

Cells communicate, or signal, with each other constantly to ensure proper functioning of tissues and organs. Cell signaling is often performed by interplay of receptors and ligands that bind these receptors. ErbB receptors (epidermal growth factor receptors, EGFR, HER) bind extracellular growth factors and transduce these signals inside of cells. ErbB dysfunction promotes carcinogenesis, and also results in numerous defects during normal development. This study focused on the functions of one member of the ErbB receptor family, ErbB4, and growth factor, neuregulin-1 (NRG-1), that can bind and activate ErbB4. This study aimed to find novel functions of ErbB4 and NRG-1. Hypoxia, or deficiency of oxygen, is common in cancer and ischemic conditions. One of the key findings of the work was the identification and characterization of a cross-talk between ErbB4 and Hypoxia-inducible factor 1α (HIF-1α), the central mediator of hypoxia signaling. ErbB4 activation by NRG-1 was found to increase HIF-1α activity. Interestingly, this regulation occurred in reciprocal manner as HIF-1α was also able to increase protein levels of NRG-1 and ErbB4. Moreover, expression of NRG-1 and ErbB4 was associated with HIF activity in vivo in human clinical samples and in mice. Reduction of functional ErbB4 in developing zebrafish embryos resulted in defects in development of the skeletal muscles. To study ErbB4 functions in pathological situation in humans, clinical samples of serous ovarian carcinoma were analyzed using tissue microarrays and real-time RT-PCR. A specific isoform of ErbB4, CYT-1, was associated with poor survival in serous ovarian cancer and increased anchorage independent growth of ovarian cancer cells in vitro. These observations demonstrate that ErbB4 and NRG-1 are essential regulators of cellular response to hypoxia, of development, and of ovarian carcinogenesis.

Single nucleotide polymorphisms at 15 codons of the prion protein gene from a scrapie-affected herd of Suffolk sheep in Brazil

Scrapie is a transmissible spongiform encephalopathy of sheeps and goats, associated with the deposition of a isoform of the prion protein (PrPsc). This isoform presents an altered conformation that leads to aggregation in the host's central nervous and lymphoreticular systems. Predisposition to the prion agent infection can be influenced by specific genotypes related to mutations in amino acids of the PrPsc gene. The most characterized mutations occur at codons 136, 154 and 171, with genotypes VRQ being the most susceptible and ARR the most resistant. In this study we have analyzed polymorphisms in 15 different codons of the PrPsc gene in sheeps from a Suffolk herd from Brazil affected by an outbreak of classical scrapie. Amplicons from the PrPsc gene, encompassing the most relevant altered codons in the protein, were sequenced in order to determine each animal's genotype. We have found polymorphisms at 3 of the 15 analyzed codons (136, 143 and 171). The most variable codon was 171, where all described alleles were identified. A rare polymorphism was found at the 143 codon in 4% of the samples analyzed, which has been described as increasing scrapie resistance in otherwise susceptible animals. No other polymorphisms were detected in the remaining 12 analyzed codons, all of them corresponding to the wild-type prion protein. Regarding the risk degree of developing scrapie, most of the animals (96%) had genotypes corresponding to risk groups 1 to 3 (very low to moderate), with only 4% in the higher risks group. Our data is discussed in relation to preventive measures involving genotyping and positive selection to control the disease.

Metallien eluointi kelatoivasta ioninvaihtimesta

Kelatoivat ioninvaihtimet ovat yleensä makrohuokoisia hartseja, joiden avulla metalleja poistetaan ja otetaan mahdollisesti talteen teollisuuden puhdistettavista jätevirroista. Ne muodostavat metalli-ionien kanssa komplekseja runkomateriaaliin kovalenttisesti liitettyjen aktiivisten funktionaalisten ryhmiensä välityksellä. Ioninvaihtimen selektiivisyys eri metalli-ioneja kohtaan vaihtelee riippuen siihen liitetystä kelatoivasta ryhmästä. Työssä tutkitaan metallien tarttumista kelatoiviin ioninvaihtimiin, sekä niiden eluoitumista adsorbentistaan. Kelatoivat ioninvaihtimet sitovat metalli-ioneja tehokkaasti ligandiensa monihampaisuudesta johtuen. Metallien tarttuminen kelatoivaan ioninvaihtimeen ei kuitenkaan ole yksiselitteistä, vaan siihen vaikuttaa muun muassa pH yhdessä monen muun tekijän kanssa. Ioninvaihtimien selektiivisyyttä tarkastellaan työssä lähinnä kovien ja pehmeiden happojen ja emästen HSAB -teorian näkökulmasta. Regeneroinnilla ioninvaihdin saadaan jälleen alkuperäiseen muotoonsa, minkä jälkeen se voidaan käyttää uudelleen. Yleensä regenerointi suoritetaan kemiallisesti. Tässä työssä ioninvaihtimien regenerointia ja kohdemetallin eluointia tarkastellaan paitsi teoriassa, myös kokeellisessa osuudessa. Kokeellisessa osuudessa tutkitaan kuparin (Cu2+) eluoitumista kelatoivasta Dowex M-4195 kationinvaihtohartsista. Kokeissa hartsi ladattiin kuparilla erillisessä panoksessa kuparin ollessa syöttöliuoksessa kuparisulfaattina. Eluointiliuoksina käytettiin 2 ja 5 molaarista rikkihappoa, sekä 2 molaarista ammoniumhydroksidia. Eluointi suoritettiin panostoimisena kolonniajona ja eluaatista otetut näytteet analysoitiin atomiadsorptiospektrofotometrillä. Analyysitulokset esitetään läpäisykäyrinä, joiden perusteella 2M ammoniumhydroksidi on kolmesta tutkitusta eluentista tehokkain eluoimaan kuparia Dowex M-4195 hartsista.

Modelling of potentiometric ion sensors

Potentiometric ion sensors are a very important subgroup of electrochemical sensors, very attractive for practical applications due to their small size, portability, low-energy consumption, relatively low cost and not changing the sample composition. They are investigated by the researchers from many fields of science. The continuous development of this field creates the necessity for a detailed description of sensor response and the electrochemical processes important in the practical applications of ion sensors. The aim of this thesis is to present the existing models available for the description of potentiometric ion sensors as well as their applicability and limitations. This includes the description of the diffusion potential occurring at the reference electrodes. The wide range of existing models, from most idealised phase boundary models to most general models, including migration, is discussed. This work concentrates on the advanced modelling of ion sensors, namely the Nernst-Planck-Poisson (NPP) model, which is the most general of the presented models, therefore the most widely applicable. It allows the modelling of the transport processes occurring in ion sensors and generating the potentiometric response. Details of the solution of the NPP model (including the numerical methods used) are shown. The comparisons between NPP and the more idealized models are presented. The applicability of the model to describe the formation of diffusion potential in reference electrode, the lower detection limit of both ion-exchanger and neutral carrier electrodes and the effect of the complexation in the membrane are discussed. The model was applied for the description of both types of electrodes, i.e. with the inner filling solution and solidcontact electrodes. The NPP model allows the electrochemical methods other than potentiometry to be described. Application of this model in Electrochemical Impedance Spectroscopy is discussed and a possible use in chrono-potentiometry is indicated. By combining the NPP model with evolutionary algorithms, namely Hierarchical Genetic Strategy (HGS), a novel method allowing the facilitation of the design of ion sensors was created. It is described in detail in this thesis and its possible applications in the field of ion sensors are indicated. Finally, some interesting effects occurring in the ion sensors (i.e. overshot response and influence of anionic sites) as well as the possible applications of NPP in biochemistry are described.

Regulation of lymphocyte response in vitro and in vivo

CD4+ T helper (Th) cells have an important role in the defence against diverse pathogens. Th cells can differentiate into several functionally distinct subtypes including Th1 and Th2 cells. Th1 cells are important for eradicating intracellular pathogens, whereas Th2 cells pro¬tect our body against extracellular parasites. However if uncontrolled, Th cells can mediate immunopathology such as asthma or allergies, but inappropriate Th response can also lead to autoimmune diseases such as multiple sclerosis or type 1 diabetes. Deeper knowledge of the regulation of the lymphocyte response both in vitro and in vivo is important for un¬derstanding the pathogenesis of immune-mediated diseases and microbe-host interactions. In the work presented in this thesis, the first goal was to elucidate the role of novel factors, PIM kinases and c-FLIP in the regulation of human Th cell differentiation. The oncogenic serine-threonine kinases of the PIM family were shown to be preferentially expressed in Th1 cells and in addition, by using RNA interference, they were also shown to be positive regulators of Th1 differentiation. The PIM depletion experiments suggest that PIM kinases promote the expression of the hallmark cytokine of Th1 cells, IFNγ, and influence the IL12/STAT4 pathway during the early Th1 cell differentiation. In addition to cytokine and T cell receptor (TCR) induced pathways, caspase activity has been shown to regulate Th cell proliferation. In the work presented in this thesis, the two isoforms of the caspase regulator protein, c-FLIP, were shown to be differentially ex¬pressed in Th1 and Th2 cells. Both of the isoforms were up-regulated in response to TCR activation, but the expression of the short isoform was selectively induced by IL4, the Th2 inducing cytokine. Furthermore, the c-FLIP isoforms had distinct and opposite roles during the early differentiation of Th1 and Th2 cells. The knockdown of the long isoform of c-FLIP led to the induction of Th1 marker genes, such as IFNγ and TBET, whereas the depletion of c-FLIP short down-regulated Th2 marker genes IL-4 and GATA3. The third goal was to elucidate the gene expression profiles characterizing the T- and B-lymphocyte responses in vivo during experimental infection by intracellular bacte¬rium Chlamydia pneumoniae. Previously, it has been shown that CD8+ and CD4+ T cells are important for the protection against Chlamydia pneumoniae. In this study, the analysis revealed up-regulation of interferon induced genes during recurrent infection underlining the importance of IFNγ secreted by Th1 and CD8+ T cells in the protection against this pathogen. Taken together, in this study novel regulators of Th cell differ¬entiation were discovered and in addition the gene expression profiles of lymphocytes induced by Chlamydia pneumoniae infection were characterized.

Turbulent heat transfer and pressure drop in pinned annular regions

Experiments were performed to determine average heat transfer coefficients and friction factors for turbulent flow through annular ducts with pin fins. The measurements were carried out by means of a double-pipe heat exchanger. The total number of pins attached to the inner wall of the annular region was 560. The working fluids were air, flowing in the annular channel, and water through the inner circular tube. The average heat transfer coefficients of the pinned air-side were obtained from the experimental determination of the overall heat transfer coefficients of the heat exchanger and from the knowledge of the average heat transfer coefficients of the circular pipe (water-side), which could be found in the pertinent literature. To attain fully developed conditions, the heat exchanger was built with additional lengths before and after the test section. The inner circular duct of the heat exchanger and the pin fins were made of brass. Due to the high thermal conductivity of the brass, the small tube thickness and water temperature variation, the surface of the internal tube was practically isothermal. The external tube was made of an industrial plastic which was insulated from the environment by means of a glass wool batt. In this manner, the outer surface of the annular channel can be considered adiabatic. The results are presented in dimensionless forms, in terms of average Nusselt numbers and friction factors as functions of the flow Reynolds number, ranging from 13,000 to 80,000. The pin fin efficiency, which depends on the heat transfer coefficient, is also determined as a function of dimensionless parameters. A comparison of the present results with those for smooth sections (without pins) is also presented. The purpose of such a comparison is to study the influence of the presence of the pins on the pressure drop and heat transfer rate.

Comparison between one-dimensional uncoupled and convection-conduction conjugated approaches in finned surface heat transfer

This work studies the forced convection problem in internal flow between concentric annular ducts, with radial fins at the internal tube surface. The finned surface heat transfer is analyzed by two different approaches. In the first one, it is assumed one-dimensional heat conduction along the internal tube wall and fins, with the convection heat transfer coefficient being a known parameter, determined by an uncoupled solution. In the other way, named conjugated approach, the mathematical model (continuity, momentum, energy and K-epsilon equations) applied to tube annuli problem was numerically solved using finite element technique in a coupled formulation. At first time, a comparison was made between results obtained for the conjugated problem and experimental data, showing good agreement. Then, the temperature profiles under these two approaches were compared to each other to analyze the validity of the one-dimensional classical formulation that has been utilized in the heat exchanger design.

Työkoneiden dieselmoottoreiden hyötysuhteen parantaminen lämmöntalteenoton avulla

Tämä diplomityö on osa Lappeenrannan teknillisessä yliopistossa tehtävää tutkimusta polttomoottoreiden energiatehokkuuden parantamisessa. Työn tavoitteena on saada tutkimustietoa polttomoottoreiden hukkalämpövirtojen hyödyntämisestä sähköntuotannossa. Tavoitteena on muodostaa näkemys Mikro-ORC energiamuuntimen mahdollisuuksista ja reunaehdoista osana työkoneluokan (150 kW… 400 kW) dieselmoottorikokonaisuutta, erityisesti maataloussektorilla. Työssä tarkasteltaviksi moottoreiksi valittiin kaksi eri AGCO Sisu Powerin dieselmoottoria. Laskennat suoritettiin moottorin valmistajan antamien hukkalämpövirtojen arvojen perusteella. Laskennan perusperiaatteena oli tutkia ORC-prosessin tuottamaa lisäsähkötehoa hyödyntämällä pakokaasujen lämpöenergiaa korkea-, keski- ja matalalämpötiloissa. Työssä vertailtiin kahden eri kiertoaineen prosessihyötysuhdetta, saatava sähkötehoa sekä prosessin sisäisiä parametreja. Lisäksi työssä tutkittiin ORC-prosessin laskentaa suunnittelupisteessä (design) ja suunnittelupisteen ulkopuolella (off-design), prosessisuureiden optimointia ja lämmönsiirtimien mitoitusta. Diplomityössä tarkasteltiin moottorin energiataseen mukaisten arvojen lisäksi moottorin parametrien muuttamisen vaikutusta hukkalämpövirroista saatavan tehoon. Työssä saatiin arvokasta tietoa polttomoottoreiden hukkalämpövirtojen muuntamisesta sähköksi ORC:lla sekä moottorin energiatehokkuuden parantamisesta.

The Effects of Fibroblast Growth Factor 8b on Reproductive Organs and Prostate Tumorigenesis

Fibroblast growth factors (FGFs) are involved in the development and homeostasis of the prostate and other reproductive organs. FGF signaling is altered in prostate cancer. Fibroblast growth factor 8 (FGF8) is a mitogenic growth factor and its expression is elevated in prostate cancer and in premalignant prostatic intraepithelial neoplasia (PIN) lesions. FGF8b is the most transforming isoform of FGF8. Experimental models show that FGF8b promotes several phases of prostate tumorigenesis - including cancer initiation, tumor growth, angiogenesis, invasion and development of bone metastasis. The mechanisms activated by FGF8b in the prostate are unclear. In the present study, to examine the tumorigenic effects of FGF8b on the prostate and other FGF8b expressing organs, an FGF8b transgenic (TG) mouse model was generated. The effect of estrogen receptor beta (ERβ) deficiency on FGF8binduced prostate tumorigenesis was studied by breeding FGF8b-TG mice with ERβ knockout mice (BERKOFVB). Overexpression of FGF8b caused progressive histological and morphological changes in the prostate, epididymis and testis of FGF8b-TG-mice. In the prostate, hyperplastic, preneoplastic and neoplastic changes, including mouse PIN (mPIN) lesions, adenocarcinomas, sarcomas and carcinosarcomas were present in the epithelium and stroma. In the epididymis, a highly cancer-resistant tissue, the epithelium contained dysplasias and the stroma had neoplasias and hyperplasias with atypical cells. Besides similar histological changes in the prostate and epididymis, overexpression of FGF8b induced similar changes in the expression of genes such as osteopontin (Spp1), connective tissue growth factor (Ctgf) and FGF receptors (Fgfrs) in these two tissues. In the testes of the FGF8b-TG mice, the seminiferous epithelium was frequently degenerative and the number of spermatids was decreased. A portion of the FGF8b-TG male mice was infertile. Deficiency of ERβ did not accelerate prostate tumorigenesis in the FGF8b-TG mice, but increased significantly the frequency of mucinous metaplasia and slightly the frequency of inflammation in the prostate. This suggests putative differentiation promoting and anti-inflammatory roles for ERβ. In summary, these results underscore the importance of FGF signaling in male reproductive organs and provide novel evidence for a role of FGF8b in stromal activation and prostate tumorigenesis.