11 resultados para Lh

em Doria (National Library of Finland DSpace Services) - National Library of Finland, Finland


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Breast cancer is the most common cancer in women, and its development is intimately related to hormonal factors, but how hormones affect breast physiology and tumorigenesis is not sufficiently known. Pregnancy elicits long-term protection from breast cancer, but during the first ten years after pregnancy, breast cancer risk is increased. In previous studies, there has been conflicting data on the role of human chorionic gonadotropin (HCG) and the functionality of its receptor in extragonadal tissues. The aim of this study was to elucidate the role of chronically elevated HCG in mouse physiology. We have created a transgenic (TG) mouse model that overexpresses HCG. HCG is similar to lutenizing hormone (LH), but is secreted almost solely by the placenta during pregnancy. HCG and LH both bind to the LH receptor (LHR). In the current study, mammary gland tumors were observed in HCG TG mice. We elucidated the role of HCG in mammary gland signalling and the effects of LHR mediated signalling in mouse mammary gland gene expression. We also studied the effects of HCG in human breast epithelial cell cultures. Several endocrine disturbances were observed in HCGβ TG female mice, resulting in precocious puberty, infertility, obesity and pituitary and mammary gland tumors. The histology of the mammary gland tumors of HCGβ TG females resembled those observed in mouse models with activated Wnt/β-catenin signalling pathway. Wnts are involved in stem cell regulation and tumorigenesis, and are hormonally regulated in the mammary gland. We observed activated β-catenin signalling and elevated expression of Wnt5b and Wnt7b in TG tumors and mammary glands. Furthermore, we discovered that HCG directly regulates the expression of Wnt5b and Wnt7b in the mouse mammary gland. Pharmacological treatment with HCG also caused upregulation of several Wnt-pathway target genes in ovariectomized wild type (WT) mice in the presence of physiological concentrations of estradiol and progesterone. In addition, differential expression of several metabolic genes was observed, suggesting that HCG affects adipocyte function or glucose metabolism. When WT mice were transplanted with LHR deficient or wild type WT mammary epithelium, differential expression of several genes affecting the Wnt-signalling pathway was observed in microarray analysis. Diminished expression of several genes associated with LHR function in other tissues, such as the ovary, was observed in mammary glands deficient of epithelial LHR. In cultured human mammary epithelial cells HCG upregulated the expression of WNT5B, WNT7B similar to mouse, suggesting that the observations found are relevant in human physiology. These studies suggest that HCG/LHR signalling affects gene expression in non-gonadal tissues, and that Wnt-signalling is regulated by HCG/LH in human and mouse mammary glands.

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Substances emitted into the atmosphere by human activities in urban and industrial areas cause environmental problems such as air quality degradation, respiratory diseases, climate change, global warming, and stratospheric ozone depletion. Volatile organic compounds (VOCs) are major air pollutants, emitted largely by industry, transportation and households. Many VOCs are toxic, and some are considered to be carcinogenic, mutagenic, or teratogenic. A wide spectrum of VOCs is readily oxidized photocatalytically. Photocatalytic oxidation (PCO) over titanium dioxide may present a potential alternative to air treatment strategies currently in use, such as adsorption and thermal treatment, due to its advantageous activity under ambient conditions, although higher but still mild temperatures may also be applied. The objective of the present research was to disclose routes of chemical reactions, estimate the kinetics and the sensitivity of gas-phase PCO to reaction conditions in respect of air pollutants containing heteroatoms in their molecules. Deactivation of the photocatalyst and restoration of its activity was also taken under consideration to assess the practical possibility of the application of PCO to the treatment of air polluted with VOCs. UV-irradiated titanium dioxide was selected as a photocatalyst for its chemical inertness, non-toxic character and low cost. In the present work Degussa P25 TiO2 photocatalyst was mostly used. In transient studies platinized TiO2 was also studied. The experimental research into PCO of following VOCs was undertaken: - methyl tert-butyl ether (MTBE) as the basic oxygenated motor fuel additive and, thus, a major non-biodegradable pollutant of groundwater; - tert-butyl alcohol (TBA) as the primary product of MTBE hydrolysis and PCO; - ethyl mercaptan (ethanethiol) as one of the reduced sulphur pungent air pollutants in the pulp-and-paper industry; - methylamine (MA) and dimethylamine (DMA) as the amino compounds often emitted by various industries. The PCO of VOCs was studied using a continuous-flow mode. The PCO of MTBE and TBA was also studied by transient mode, in which carbon dioxide, water, and acetone were identified as the main gas-phase products. The volatile products of thermal catalytic oxidation (TCO) of MTBE included 2-methyl-1-propene (2-MP), carbon monoxide, carbon dioxide and water; TBA decomposed to 2-MP and water. Continuous PCO of 4 TBA proceeded faster in humid air than dry air. MTBE oxidation, however, was less sensitive to humidity. The TiO2 catalyst was stable during continuous PCO of MTBE and TBA above 373 K, but gradually lost activity below 373 K; the catalyst could be regenerated by UV irradiation in the absence of gas-phase VOCs. Sulphur dioxide, carbon monoxide, carbon dioxide and water were identified as ultimate products of PCO of ethanethiol. Acetic acid was identified as a photocatalytic oxidation by-product. The limits of ethanethiol concentration and temperature, at which the reactor performance was stable for indefinite time, were established. The apparent reaction kinetics appeared to be independent of the reaction temperature within the studied limits, 373 to 453 K. The catalyst was completely and irreversibly deactivated with ethanethiol TCO. Volatile PCO products of MA included ammonia, nitrogen dioxide, nitrous oxide, carbon dioxide and water. Formamide was observed among DMA PCO products together with others similar to the ones of MA. TCO for both substances resulted in the formation of ammonia, hydrogen cyanide, carbon monoxide, carbon dioxide and water. No deactivation of the photocatalyst during the multiple long-run experiments was observed at the concentrations and temperatures used in the study. PCO of MA was also studied in the aqueous phase. Maximum efficiency was achieved in an alkaline media, where MA exhibited high fugitivity. Two mechanisms of aqueous PCO – decomposition to formate and ammonia, and oxidation of organic nitrogen directly to nitrite - lead ultimately to carbon dioxide, water, ammonia and nitrate: formate and nitrite were observed as intermediates. A part of the ammonia formed in the reaction was oxidized to nitrite and nitrate. This finding helped in better understanding of the gasphase PCO pathways. The PCO kinetic data for VOCs fitted well to the monomolecular Langmuir- Hinshelwood (L-H) model, whereas TCO kinetic behaviour matched the first order process for volatile amines and the L-H model for others. It should be noted that both LH and the first order equations were only the data fit, not the real description of the reaction kinetics. The dependence of the kinetic constants on temperature was established in the form of an Arrhenius equation.

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Aims: The aims were to create clinically feasible reference intervals for thyroidstimulating hormone (TSH) and free thyroxine (FT4) and to analyze associations between thyroid function and self-rated health, neuropsychiatric symptoms, depression and dementia in the elderly. The second aim was also to establish reference intervals for sex hormones and to analyze associations between sex hormone levels and self-rated health, symptoms, depression and dementia in elderly men. Subjects and methods: The study population comprised 1252 subjects aged 65 years or over, living in the municipality of Lieto, south-western Finland. Self-rated health, life satisfaction, symptoms, depression, and dementia were assessed with specific questions, clinical examination and tools such as the Zung Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH, FT4 or sex hormone levels were assessed. Levels of TSH and FT4 in thyroid disease–free women and women treated with thyroxine were also compared. Results: Elevated concentrations of thyroid peroxidase antibodies (TPOAb) or thyroglobulin antibodies (TgAb) were found to have a marked effect on the upper reference limit for TSH among women, who were thyroid antibody positive more higher than suggested in several recent guidelines. After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most neuropsychiatric symptoms in the thyroid disease-free population. Although women with thyroxine treatment for primary hypothyroidism had far higher TSH levels than thyroid disease-free women, there were no differences between thyroid-disease free women and women with stable thyroxine treatment regarding self-rated health, life satisfaction or symptoms. Age had a significant positive association with luteinizing hormone (LH), follicle 2 practice, one range in men aged 65 years or over can be used for T, E2 and FSH measured with the AutoDelfia method, but two separate reference intervals should be used for fT, LH and SHBG. After adjustment for age, higher levels of T and fT were associated with better self-rated health (SRH) in the reference population. After adjustment for age and body mass index (BMI), there were no associations between sex hormone concentrations and self-rated health, life satisfaction or most symptoms in concentration. Conclusion: Age-specific reference intervals were derived for thyroid function and sex hormones based on comprehensive data from a community-dwelling population with a high participation rate. The results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines. Older age or being overweight symptoms among elderly men. The associations of single symptoms with T levels were inconsistent among elderly men, although the association of low T level with diagnosed depression might be clinically significant.

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Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are structurally and functionally similar glycoprotein hormones acting through the same luteinizing hormone chorionic gonadotropin receptor (LHCGR). The functions of LH in reproduction and hCG in pregnancy are well known. Recently, the expression of LHCGR has been found in many nongonadal tissues and cancers, and this has raised the question of whether LH/hCG could affect the function or tumorigenesis of these nongonadal tissues. We have also previously generated an hCG expressing mouse model presenting nongonadal phenotypes. Using this model it is possible to improve our understanding of nongonadal action of highly elevated LH/hCG. In the current study, we analyzed the effect of moderately and highly elevated hCG levels on male reproductive development and function. The main finding was the appearance of fetal Leydig cell (FLC) adenomas in prepubertal males. However, the development and differentiation of FLCs were not significantly affected. We also show that the function of hCG is different in FLCs and in adult Leydig cells (ALC), because in the latter cells hCG was not able to induce tumorigenesis. In FLCs, LHCGR is not desensitized or downregulated upon ligand binding. In this study, we found that the testicular expression of two G protein-coupled receptor kinases responsible for receptor desensitization or downregulation is increased in adult testis. Results suggest that the lack of LHCGR desensitization or downregulation in FLCs protect testosterone (Te) synthesis, but also predispose FLCs for LH/hCG induced adenomas. However, all the hCG induced nongonadal changes observed in male mice were possible to explain by the elevated Te level found in these males. Our findings indicate that the direct nongonadal effects of elevated LH/hCG in males are not pathophysiologically significant. In female mice, we showed that an elevated hCG level was able to induce gonadal tumorigenesis. hCG also induced the formation of pituitary adenomas (PA), but the mechanism was indirect. Furthermore, we found two new potential risk factors and a novel hormonally induced mechanism for PAs. Increased progesterone (P) levels in the presence of physiological estradiol (E2) levels induced the formation of PAs in female mice. E2 and P induced the expression and nuclear localization of a known cell-cycle regulator, cyclin D1. A calorie restricted diet was also able to prevent the formation of PAs, suggesting that obesity is able to promote the formation of PAs. Hormone replacement therapy after gonadectomy and hormone antagonist therapy showed that the nongonadal phenotypes observed in hCG expressing female mice were due to ovarian hyperstimulation. A slight adrenal phenotype was evident even after gonadectomy in hCG expressing females, but E2 and P replacement was able to induce a similar phenotype in WT females without elevated LH/hCG action. In conclusion, we showed that the direct effects of elevated hCG/LH action are limited only to the gonads of both sexes. The nongonadal phenotypes observed in hCG expressing mice were due to the indirect, gonadal hormone mediated effects of elevated hCG. Therefore, the gonads are the only physiologically significant direct targets of LHCGR signalling.

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Opinnäytetyö keskittyi kriittisiin tapahtumiin, joita on tullut yhtiön tai sen edeltävän yhtiön, joka oli Mobile Screen TV – 4 ALL, tekemien aikaisempien patenttihakemusten yhteydessä . Tutkimus vertasi ja evaluoi yhtiön aikaisemmin tekemien keksintöjen suojausta. Toisaalta opinnäytetyön päämäärä oli tutkia ja selvittää monitapaus-menetelmällä yhtiön aikaisempia keksintöjä ja miten aineettoman oikeuden suojaus toteutui prosessien eri vaiheissa. Tämä päättötyötutkielma vei loppuun asti erittäin suuren patenttien ja hyödyllisyysmallien hakemusten tutkimuksen. LH Communications Oy on tehnyt monia niistä, mutta tutkimus sisälsi myös joitakin kilpailijoiden hakemuksia. Tässä tutkimuksessa oli kaksi pääkysymystä. Miten pieni yhtiö voisi suojella heidän uusia ideoitaan ja keksintöjään ja myös samalla pitää yhtiön talouden hyvällä tasolla. Tämä tutkimus käytti The Critical Incidents Technique (CIT), joka keskittyy kriittisiin tapahtumiin, selvittääkseen sopivia menetelmiä pienelle yhtiölle siitä, miten suojella uusia ajatuksia, ideoita ja keksintöjä ja samanaikaisesti olla tuottava niiden kanssa. Tutkimuksemme käsitteli kaikenlaisia tarvittavia käytäntöjä pienessä yhtiössä ja päähuomio pienessä yhtiössä tulee olla omien keksintöjen suojaamisessa. Paras suojaus on tehdä patentteja, mutta se tulee maksamaan hyvin paljon koko tapahtumasarjan aikana.

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Hawthorn (Crataegus sp.) is widely distributed in the northern hemisphere (Asia, Europe and North America). It has been used as a medicinal material and food for hundreds of years both in Europe and in China. Clinical investigations and other research suggest that extracts of hawthorn fruits and leaves have multiple health effects including hypolipidaemic, anti-atherosclerotic, hypotensive, cardioprotective and blood vessel relaxing activities. Hawthorn fruit extracts have also displayed antioxidant and radical scavenging activities. Emblic leafflower fruit (Phyllanthus emblica) is widely used in Chinese and Indian traditional medicine. It has been found to have anti-cancer, hypoglycaemic and hypolipidaemic activities as well as cardioprotective effects and antioxidant activity. The fruit is currently used as a functional food targeted at obese people in China. Phenolic compounds, procyanidins (PCs), flavonols and C-glycosyl flavones in hawthorn and hydrolysable tannins in emblic leafflower fruits are considered among the major bioactive compounds in these berries. Moreover, hawthorn and emblic leafflower fruits are rich in vitamin C, triterpenoids, fruit acids, sugar alcohols and some other components with beneficial effects on the health of human beings. The aim of the thesis work was to characterise the major phenolic compounds in hawthorn fruits and leaves and emblic leafflower fruits as well as other components contributing to the nutritional profile and sensory properties of hawthorn fruits. Differences in the content and compositional profile of the major phenolic compounds, sugars, acids and sugar alcohols within various origins and species of hawthorn were also investigated. Acids, sugars and sugar alcohols in the fruits of different origins/cultivars belonging to three species (C. pinnatifida, C. brettschneideri and C. scabrifolia) of hawthorn were analysed by gas chromatography (GC-FID) and mass spectrometry (Publication I). Citric acid, quinic acid, malic acid, fructose, glucose, sorbitol and myo-inositol were found in all the subspecies. Sucrose was present only in C. scabrifolia and three cultivars of C. pinnatifida var. major. Forty-two phenolic compounds were identified/tentatively identified in fruits of C. pinnatifida var. major by polyamide column chromatography combined with high-performance liquid chromatograph-electrospray ionisation mass spectrometry (HPLC-ESI-MS) (Publication II). Ideain, chlorogenic acid, procyanidin (PC) B2, (-)-epicatechin, hyperoside and isoquercitrin were the major phenolic components identified. In addition, 35 phenolic compounds were tentatively identified based on UV and mass spectra. Eleven major phenolic compounds (hyperoside, isoquercitrin, chlorogenic acid, ideain, (-)-epicatechin, two PC dimers, three PC trimers and a PC dimer-hexoside) were quantified in the fruits of 22 cultivars/origins of three species of Chinese hawthorn by HPLC-ESI-MS with single ion recording function (SIR) (Publication III). The fruits of the hawthorn cultivars/origins investigated fell into two groups, one rich in sugars and flavonols, the other rich in acids and procyanidins. Based on the compositional features, different biological activities and sensory properties may be expected between cultivars/origins of the two groups. The results suggest that the contents of phenolic compounds, acids, sugars and sugar alcohols may be used as chemotaxonomic information distinguishing the hawthorn species from each other. Phenolic compounds in fruits and leaves of C. grayana and their changes during fruit ripening/harvesting were investigated using HPLC-UV-ESI-MS (Publication IV). (-)-Epicatechin, PC B2 and C1, hyperoside and a quercetin-pentoside were the major phenolic compounds in both fruits and leaves. Three C-glycosyl flavones (a luteolin-C-hexoside, a methyl luteolin-C-hexoside and an apigenin-C-hexoside) were present in leaves in abundance, but only at trace levels in fruits. Ideain and 5-O-caffeoylquinic acid were found in fruits only. Additionally, eleven phenolic compounds were identified/tentatively identified in both leaves and fruits (three B-type PC trimers, two B-type PC tetramers, a quercetin-rhamnosylhexoside, a quercetin-pentoside, a methoxykaempferol-methylpentosylhexoside, a quercetin-hexoside acetate, a methoxykaempferol-pentoside, chlorogenic acid and an unknown hydroxycinnamic acid derivative). The total content of phenolic compounds reached the highest level by the end of August in fruits and by the end of September in leaves. The compositional profiles of phenolic compounds in fruits and leaves of C. grayana were different from those of C. pinnatifida, C. brettschneideri, C. scabrifolia, C. pinnatifida. var. major, C. monogyna, C. laevigata and C. pentagyna. Phenolic compounds in emblic leafflower fruits were characterised by Sephadex LH-20 column chromatography combined with HPLC-ESI-MS (Publication V). A mucic acid gallate, three isomers of mucic acid lactone gallate, a galloylglucose, gallic acid, a digalloylglucose, putranjivain A, a galloyl-HHDP-glucose, elaeocarpusin and chebulagic acid represented the major phenolic compounds in fruits of emblic leafflower. In conclusion, results of this study significantly increase the current knowledge on the key bioactive and nutritional components of hawthorn and emblic leafflower fruits. These results provide important information for research on the mechanism responsible for the health benefits of these fruits.

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Valtaosassa nykyaikana käytössä olevista hävittäjistä aseistus, lisäpolttoainesäiliöt ja maa-linosoitusjärjestelmät kiinnitetään koneen ulkopuolelle joko siipi- tai runkoripustimiin. Tämä on yksinkertainen tapa, mutta se lisää koneen vastusta ja näin ollen heikentää sen suoritusky-kyä. Siiven alle kiinnitetty kuorma vaikuttaa myös nostovoimaan häiritsemällä siiven ympä-rillä kulkevaa virtausta. Lisäksi ulkoinen kuorma aiheuttaa usein rajoituksia suurimpaan sal-littuun kuormitusmonikertaan, jolloin koneen liikehtimis- ja kaartokyky heikkenevät. Tässä kandidaatintutkielmassa selvitetään miten ulkoinen kuorma vaikuttaa hävittäjän suori-tuskykyyn ja edellä mainittuihin ominaisuuksiin. Havainnot esitellään ja perustellaan enim-mäkseen laskennallisesti aerodynamiikan kaavoja apuna käyttäen. Tutkielmassa käytetään kvalitatiivista tutkimusstrategiaa ja sen tutkimusmenetelmänä on kirjallisuusanalyysi. Läh-teinä on käytetty aerodynamiikan peruskirjallisuutta, eri korkeakoulujen oppimateriaaleja, Koelentokeskuksen materiaalia sekä ulkomaisia tutkimuksia. Tutkielman päätutkimuskysymys on: ”Miten ulkoinen kuorma vaikuttaa hävittäjän suoritus-kykyyn?”. Alatutkimuskysymyksiä ovat: ”Miten ulkoinen kuorma vaikuttaa hävittäjän vas-tukseen?”, ”Miten ulkoinen kuorma vaikuttaa hävittäjän nostovoimaan?” ja ”Miten ulkoinen kuorma vaikuttaa hävittäjän kaartokykyyn?”. Kun koneeseen lisätään ulkoista kuormaa, sen sakkausnopeus kasvaa, parhaan liitosuhteen nopeus pienenee, lentoonlähdön maakiito pitenee ja kohoamisnopeus heikkenee. Lisäksi polttoaineen kulutus kasvaa ja tätä kautta kantama ja toiminta-aika lyhenevät. Joissain tapa-uksissa koneen maksiminopeuksiin saattaa tulla rajoituksia, ja etenkin suurella kuormalla lennon rajakäyrä supistuu huomattavasti. Edellä mainitut yhdistettynä mahdollisiin kuormi-tusmonikerran rajoituksiin heikentävät koneen kaartokykyä ilmataistelussa. Voidaankin sa-noa, että ulkoinen kuorma heikentää koneen suorituskykyä sen kaikilla osa-alueilla.

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Yritysvarallisuus on nykyään yhä aineettomampaa. Osan tästä yritysten aineettomasta varallisuu-desta muodostavat erilaiset immateriaalioikeudet, jotka voivat olla joko rekisteröityjä kansallisiin tai kansainvälisiin rekistereihin tai vaihtoehtoisesti saada suojaa ilman rekisteröintiä. Ilman rekisteröintiä suojataan muun muassa tekijänoikeutta, vakiintunutta tavaramerkkiä ja toiminimeä sekä lii-kesalaisuuksia. Myös teollisoikeushakemukset, kuten vireillä olevat patenttihakemukset, eivät läh-tökohtaisesti ole kirjattuja julkisiin rekistereihin. Kirjaamattomat immateriaalioikeudet ovat yrityksille varallisuusarvoista omaisuutta, jota yritysten tulisi kyetä käyttämään taloudellisesti hyödyksi eri tavoin. Yrityksille saattaa muodostua muun mu-assa tarve hyödyntää kyseisiä oikeuksia rahoituksen tai muun luoton vakuutena. Tutkielmassa tar-kastellaan kirjaamattomien immateriaalioikeuksien yleistä vakuuskelpoisuutta esinevakuusoikeuden yleisten oppien valossa ja selvitetään sitten vakuuskäytön mahdollisuutta eri vakuusmuotojen kautta. Ongelmaksi tiettyjen kirjaamattomien immateriaalioikeuksien vakuuskelpoisuuden kohdalla muodostuu erityisesti järjestelylle sivullissitovuuden tuovan julkivarmistuksen toteuttamiskeinojen puute, sillä vakuusjärjestelyä ei voi tuoda julkiseksi kirjaamalla sitä asianomaiseen rekisteriin kuten rekisteröityjen immateriaalioikeuksien kohdalla on mahdollista. Tutkimuksessa tarkastellaan kirjaamattomien immateriaalioikeuksien vakuuskäytön mahdollisuutta panttauksen, vakuusluovutuksen, yrityskiinnityksen sekä oikeuden yhtiöittämisen kautta. Julkivar-mistuksen vaatimus on vahvimmillaan perinteisessä panttioikeudessa, eikä oikeuskirjallisuuden va-kiintuneen kannan mukaan panttaus ole omaisuuden julkivarmistuskelvottomuudesta johtuen mah-dollista. Vakuusluovutuksen asema oikeusjärjestyksessä on edelleen epäselvä, vaikka sen käyttöä puolletaankin toisinaan perustellen sitä juuri julkivarmistuskelvottomien omaisuuserien panttausta korvaavana järjestelmänä. Myös yrityskiinnityksen ja yhtiöittämismenettelyn kautta kirjaamattomat immateriaalioikeudet voidaan tietyin edellytyksin saada vakuuskelpoisuuden piiriin. Tutkielma on lainopillinen ja pyrkii selvittämään kirjaamattomien immateriaalioikeuksien vakuus-kelpoisuutta voimassa olevan oikeuden sekä oikeuskirjallisuuden valossa. Oikeuspoliittinen tutki-musote ilmenee tutkimuksessa esitettyjen ratkaisuehdotusten kautta, sillä kirjaamattomien immate-riaalioikeuksien vakuuskäytön mahdollistamiselle on olemassa selkeä tarve. Niin kauan kuin oikeu-den tila pysyy epäselvänä, jää tällaisten omaisuuserien täysi vakuuspotentiaali hyödyntämättä.