Associations of gene polymorphisms and nutrition with calcium homeostasis and bone mineral density : Studies on skeletal nutrigenetics

Heredity explains a major part of the variation in calcium homeostasis and bone strength, and the susceptibility to osteoporosis is polygenetically regulated. Bone phenotype results from the interplay between lifestyle and genes, and several nutritional factors modulate bone health throughout life. Thus, nutrigenetics examining the genetic variation in nutrient intake and homeostatic control is an important research area in the etiology of osteoporosis. Despite continuing progress in the search for candidate genes for osteoporosis, the results thus far have been inconclusive. The main objective of this thesis was to investigate the associations of lactase, vitamin D receptor (VDR), calcium sensing receptor (CaSR) and parathyroid hormone (PTH) gene polymorphisms and lifestyle factors and their interactions with bone health in Finns at varying stages of the skeletal life span. Markers of calcium homeostasis and bone remodelling were measured from blood and urine samples. Bone strength was measured at peripheral and central bone sites. Lifestyle factors were assessed with questionnaires and interviews. Genetic lactase non-persistence (the C/C-13910 genotype) was associated with lower consumption of milk from childhood, predisposing females in particular to inadequate calcium intake. Consumption of low-lactose milk and milk products was shown to decrease the risk for inadequate calcium intake. In young adulthood, bone loss was more common in males than in females. Males with the lactase C/C-13910 genotype may be more susceptible to bone loss than males with the other lactase genotypes, although calcium intake predicts changes in bone mass more than the lactase genotype. The BsmI and FokI polymorphisms of the VDR gene were associated with bone mass in growing adolescents, but the associations weakened with age. In young adults, the A986S polymorphism of the calcium sensing receptor gene was associated with serum ionized calcium concentrations, and the BstBI polymorphism of the parathyroid gene was related to bone strength. The FokI polymorphism and sodium intake showed an interaction effect on urinary calcium excretion. A novel gene-gene interaction between the VDR FokI and PTH BstBI gene polymorphisms was found in the regulation of PTH secretion and urinary calcium excretion. Further research should be carried out with more number of Finns at varying stages of the skeletal life span and more detailed measurements of bone strength. Research should concern mechanisms by which genetic variants affect calcium homeostasis and bone strength, and the role of diet-gene and gene-gene interactions in the pathogenesis of osteoporosis.

Service-based Requirements for Future Mobile Networks

The mobile phone has, as a device, taken the world by storm in the past decade; from only 136 million phones globally in 1996, it is now estimated that by the end of 2008 roughly half of the worlds population will own a mobile phone. Over the years, the capabilities of the phones as well as the networks have increased tremendously, reaching the point where the devices are better called miniature computers rather than simply mobile phones. The mobile industry is currently undertaking several initiatives of developing new generations of mobile network technologies; technologies that to a large extent focus at offering ever-increasing data rates. This thesis seeks to answer the question of whether the future mobile networks in development and the future mobile services are in sync; taking a forward-looking timeframe of five to eight years into the future, will there be services that will need the high-performance new networks being planned? The question is seen to be especially pertinent in light of slower-than-expected takeoff of 3G data services. Current and future mobile services are analyzed from two viewpoints; first, looking at the gradual, evolutionary development of the services and second, through seeking to identify potential revolutionary new mobile services. With information on both current and future mobile networks as well as services, a network capability - service requirements mapping is performed to identify which services will work in which networks. Based on the analysis, it is far from certain whether the new mobile networks, especially those planned for deployment after HSPA, will be needed as soon as they are being currently roadmapped. The true service-based demand for the "beyond HSPA" technologies may be many years into the future - or, indeed, may never materialize thanks to the increasing deployment of local area wireless broadband technologies.

Describing and validating functional requirements as use cases

Requirements engineering is an important phase in software development where customer's needs and expectations are transformed into a software requirements specification. The requirements specification can be considered as an agreement between the customer and the developer where both parties agree on the expected system features and behaviour. However, requirements engineers must deal with a variety of issues that complicate the requirements process. The communication gap between the customer and the developers is among typical reasons for unsatisfactory requirements. In this thesis we study how the use case technique could be used in requirements engineering in bridging the communication gap between the customer and development team. We also discuss how a use case description can be use cases can be used as a basis for acceptance test cases.

Communities of wood-inhabiting fungi : Ecological requirements and responses to forest management and fragmentation

Despite much research on forest biodiversity in Fennoscandia, the exact mechanisms of species declines in dead-wood dependent fungi are still poorly understood. In particular, there is only limited information on why certain fungal species have responded negatively to habitat loss and fragmentation, while others have not. Understanding the mechanisms behind species declines would be essential for the design and development of ecologically effective and scientifically informed conservation measures, and management practices that would promote biodiversity in production forests. In this thesis I study the ecology of polypores and their responses to forest management, with a particular focus on why some species have declined more than others. The data considered in the thesis comprise altogether 98,318 dead-wood objects, with 43,085 observations of 174 fungal species. Out of these, 1,964 observations represent 58 red-listed species. The data were collected from 496 sites, including woodland key habitats, clear-cuts with retention trees, mature managed forests, and natural or natural-like forests in southern Finland and Russian Karelia. I show that the most relevant way of measuring resource availability can differ to a great extent between species seemingly sharing the same resources. It is thus critical to measure the availability of resources in a way that takes into account the ecological requirements of the species. The results show that connectivity at the local, landscape and regional scales is important especially for the highly specialized species, many of which are also red-listed. Habitat loss and fragmentation affect not only species diversity but also the relative abundances of the species and, consequently, species interactions and fungal successional pathways. Changes in species distributions and abundances are likely to affect the food chains in which wood-inhabiting fungi are involved, and thus the functioning of the whole forest ecosystem. The findings of my thesis highlight the importance of protecting well-connected, large and high-quality forest areas to maintain forest biodiversity. Small habitat patches distributed across the landscape are likely to contribute only marginally to protection of red-listed species, especially if habitat quality is not substantially higher than in ordinary managed forest, as is the case with woodland key habitats. Key habitats might supplement the forest protection network if they were delineated larger and if harvesting of individual trees was prohibited in them. Taking the landscape perspective into account in the design and development of conservation measures is critical while striving to halt the decline of forest biodiversity in an ecologically effective manner.

Country-scale carbon accounting of the vegetation and mineral soils of Finland

The increase in global temperature has been attributed to increased atmospheric concentrations of greenhouse gases (GHG), mainly that of CO2. The threat of severe and complex socio-economic and ecological implications of climate change have initiated an international process that aims to reduce emissions, to increase C sinks, and to protect existing C reservoirs. The famous Kyoto protocol is an offspring of this process. The Kyoto protocol and its accords state that signatory countries need to monitor their forest C pools, and to follow the guidelines set by the IPCC in the preparation, reporting and quality assessment of the C pool change estimates. The aims of this thesis were i) to estimate the changes in carbon stocks vegetation and soil in the forests in Finnish forests from 1922 to 2004, ii) to evaluate the applied methodology by using empirical data, iii) to assess the reliability of the estimates by means of uncertainty analysis, iv) to assess the effect of forest C sinks on the reliability of the entire national GHG inventory, and finally, v) to present an application of model-based stratification to a large-scale sampling design of soil C stock changes. The applied methodology builds on the forest inventory measured data (or modelled stand data), and uses statistical modelling to predict biomasses and litter productions, as well as a dynamic soil C model to predict the decomposition of litter. The mean vegetation C sink of Finnish forests from 1922 to 2004 was 3.3 Tg C a-1, and in soil was 0.7 Tg C a-1. Soil is slowly accumulating C as a consequence of increased growing stock and unsaturated soil C stocks in relation to current detritus input to soil that is higher than in the beginning of the period. Annual estimates of vegetation and soil C stock changes fluctuated considerably during the period, were frequently opposite (e.g. vegetation was a sink but soil was a source). The inclusion of vegetation sinks into the national GHG inventory of 2003 increased its uncertainty from between -4% and 9% to ± 19% (95% CI), and further inclusion of upland mineral soils increased it to ± 24%. The uncertainties of annual sinks can be reduced most efficiently by concentrating on the quality of the model input data. Despite the decreased precision of the national GHG inventory, the inclusion of uncertain sinks improves its accuracy due to the larger sectoral coverage of the inventory. If the national soil sink estimates were prepared by repeated soil sampling of model-stratified sample plots, the uncertainties would be accounted for in the stratum formation and sample allocation. Otherwise, the increases of sampling efficiency by stratification remain smaller. The highly variable and frequently opposite annual changes in ecosystem C pools imply the importance of full ecosystem C accounting. If forest C sink estimates will be used in practice average sink estimates seem a more reasonable basis than the annual estimates. This is due to the fact that annual forest sinks vary considerably and annual estimates are uncertain, and they have severe consequences for the reliability of the total national GHG balance. The estimation of average sinks should still be based on annual or even more frequent data due to the non-linear decomposition process that is influenced by the annual climate. The methodology used in this study to predict forest C sinks can be transferred to other countries with some modifications. The ultimate verification of sink estimates should be based on comparison to empirical data, in which case the model-based stratification presented in this study can serve to improve the efficiency of the sampling design.

Cereal alkylresorcinols as dietary biomarkers-absorption and occurrence in biological membranes

Several studies link the consumption of whole-grain products to a lowered risk of chronic diseases, such as certain types of cancer, type II diabetes, and cardiovascular diseases. However, the final conclusions of the exact protective mechanisms remain unclear, partly due to a lack of a suitable biomarker for the whole-grain cereals intake. Alkylresorcinols (AR) are phenolic lipids abundant in the outer parts of wheat and rye grains usually with homologues of C15:0- C25:0 alkyl chains, and are suggested to function as whole-grain biomarkers. Mammalian lignan enterolactone has also previously been studied as a potential whole-grain biomarker. In the present work a quantified gas chromatography-mass spectrometry method for the analysis of AR in plasma, erythrocytes, and lipoproteins was developed. The method was used to determine human and pig plasma AR concentrations after the intake of whole-grain wheat and rye products compared to low-fibre wheat bread diets to assess the usability of AR as biomarkers of whole-grain intake. AR plasma concentrations were compared to serum ENL concentrations. AR absorption and elimination kinetics were investigated in a pig model. AR occurrence in human erythrocyte membranes and plasma lipoproteins were determined, and the distribution of AR in blood was evaluated. Plasma AR seem to be absorbed via the lymphatic system from the small intestine, like many other lipophilic compounds. Their apparent elimination half-life is relatively short and is similar to that of tocopherols, which have a similar chemical structure. Plasma AR concentrations increased significantly after a one- to eight-week intake of whole-grain wheat and further on with whole-grain rye bread. The concentrations were also higher after habitual Finnish diet compared to diet with low-fibre bread. Inter-individual variation after a one-week intake of the same amount of bread was high, but the mean plasma AR concentrations increased with increasing AR intake. AR are incorporated into erythrocyte membranes and plasma lipoproteins, and VLDL and HDL were the main AR carriers in human plasma. Based on these studies, plasma AR could function as specific biomarkers of dietary whole-grain products. AR are exclusively found in whole-grains and are more suitable as specific biomarkers of whole-grain intake than previously investigated mammalian lignan enterolactone, that is formed from several plants other than cereals in the diet. Plasma AR C17:0/C21:0 -ratio could distinguish whether whole-grain products in the diet are mainly wheat or rye. AR could be used in epidemiological studies to determine whole-grain intake and to better assess the role of whole-grains in disease prevention.

Lihaluujauhon soveltuvuus sokerijuurikkaan lannoitteeksi

Lihaluujauho muodostaa maatilojen myytävien kasvi- ja eläinperäisten tuotteiden jälkeen tärkeimmän agroekosysteemeistä poispäin suuntautuvan ravinnevirran. Se sisältää runsaasti pääkasvinravinteita typpeä, fosforia ja kalsiumia (N ~8%, P ~5%, Ca yleensä ~10-15% luuaineksen määrästä riippuen), sekä kaliumia n.1% tai alle. Lihaluujauho on todettu tehokkaaksi lannoitteeksi useilla viljelykasveilla ja sen käyttö on sallittu myös luomuviljelyssä EU-alueella. Lihaluujauhoon ja erityisesti sen rehukäyttöön liittyvistä riskeistä merkittävin on TSE-tautien riski (naudan BSE-, lampaiden ja vuohien scrapie-, sekä ihmisen vCJD-taudit). Rehukäyttöä on monissa maissa rajoitettu 1980-luvulla puhjenneen BSE-kriisin myötä. BSE-taudin leviäminen yhdistettiin tilanteeseen, jossa nautaperäistä lihaluujauhoa käytettiin nautaeläinten rehun ainesosana. Myös lihaluujauhon käytössä turkiseläinrehuna saattaa piillä BSE:n tai muun TSE-taudin riski. Oikein käsitellyn lihaluujauhon lannoitekäyttöön ei kuitenkaan näytä tarkastelemieni tutkimusten perusteella sisältyvän huomattavaa TSEriskiä, jos huolehditaan asianmukaisista varotoimista ja menettelyistä sekä tuotteen valmistusprosessissa, että käytettäessä lannoitetta. Lihaluujauhon lannoitekäytön lisääminen edistäisi ruokajärjestelmämme ravinnekierron sulkemista etenkin fosforin osalta. Lihaluujauho on uusiutuva luonnonvara, jonka lannoitekäytöllä voitaisiin korvata huomattava osa lannoiteaineena kulutettavista fosforipitoisista kiviaineista. Sokerijuurikkaan lannoituskokeissa Varsinais-Suomen Kaarinassa vuosina 2008 ja 2009 lihaluujauhokäsittelyt eivät menestyneet aivan yhtä hyvin satotasovertailussa kuin kontrollikäsittelyiden NPK-väkilannoitteet, mutta laatuominaisuuksiltaan (sokeripitoisuus, amino-N, K, ja Na-pitoisuudet) joiltakin osin kontrollikäsittelyjä paremmin. Kokeissa käytetyt lajikkeet olivat ’Jesper’ vuonna 2008 ja ’Lincoln’ vuonna 2009. Käytetty lihaluujauholannoite oli Honkajoki Oy:n Viljo Yleislannoite 8-4-3, joka sisälsi noin 10% kaliumsulfaatin ja kasviperäisten sivutuotteiden seosta. Viljo-lannoitetta käytettiin sekä yksistään, että yhdistettynä 10-25%:iin väkilannoitetta. Vuoden 2009 Viljo-koejäseniin vielä lisättiin kaliumsulfaattilannoitetta (42% K, 18% S), jotta päästiin annetun kaliumin määrässä päästiin lannoitussuosituksen (60 kg K/ha) tasolle. Pelkkä Viljo-lannoite tuotti merkitsevästi alhaisemmat sadot kuin kontrollikäsittelyt molempina vuosina. Kuitenkin kun Viljolannoitteen ohella käytettiin väkilannoitetta (10-25% kasvin typentarpeesta) päästiin varsin lähelle kontrollikäsittelyiden satotasoja. Myös pelkän LLJ-lannoitteen tuottamat satotasot olivat kuitenkin selvästi paremmat kuin Suomen keskimääräiset juurikassadot. Viljo-käsittelyillä oli selvästi positiivinen vaikutus laatutekijöihin amino-N, K ja Na vuonna 2008, mutta vuonna 2009 näiden pitoisuudet jäivät kontrollikäsittelyjen tasolle. Viljo-käsittelyiden sokeripitoisuudet olivat vuonna 2008 kontrollikäsittelyn luokkaa ja Viljo77%+NK1:n osalta kontrollia merkitsevästi paremmat. Vuoden 2009 sokeripitoisuudet olivat kaikilla koejäsenillä erinomaiset, ja käsittelyiden välillä ei ilmennyt merkitseviä eroja. Kokeiden perusteella kaliumsulfaatilla täydennetty lihaluujauho on hyvin toimiva lannoite sokerijuurikkaalla Suomen olosuhteissa, etenkin yhdistettynä väkilannoitteeseen.

Vitamin E may affect the life expectancy of men, depending on dietary vitamin C intake and smoking

Background: Antioxidants might protect against oxidative stress, which has been suggested as a cause of aging. Methods: The ATBC Study recruited males aged 50-69 years who smoked at least 5 cigarettes per day at the baseline. The current study was restricted to participants who were followed up past the age of 65. Deaths were identified in the National Death Registry (1445 deaths). We constructed Kaplan-Meier survival curves for all participants, and for four subgroups defined by dietary vitamin C intake and level of smoking. We also constructed Cox regression models allowing a different vitamin E effect for low and high age ranges. Results: Among all 10,837 participants, vitamin E had no effect on those who were 65 to 70 years old, but reduced mortality by 24% when participants were 71 or older. Among 2284 men with dietary vitamin C intakes above the median who smoked less than a pack of cigarettes per day, vitamin E extended life-span by two years at the upper limit of the follow-up age span. In this subgroup, the survival curves of vitamin E and no-vitamin E participants diverged at 71 years. In the other three subgroups covering 80% of the participants, vitamin E did not affect mortality. Conclusions: This is the first study to strongly indicate that protection against oxidative stress can increase the life expectancy of some initially healthy population groups. Nevertheless, the lack of effect in 80% of this male cohort shows that vitamin E is no panacea for extending life expectancy.

The Impact of New Capital Requirements on the Portfolio Decisions of Finnish Pension Institutions

This paper examines the potential impact of new capital requirements on asset allocations of Finnish pension institutions. We describe the new requirements and consider portfolio construction to minimize regulatory capital, given the investor’s preferred level of expected return. Results identify portfolio transactions that enhance expected return without increasing capital needs. Regulation calls for portfolio diversification and prudence in management, but this paper shows that market participants can exploit inconsistencies in regulation. Possible future consequences include capital outflows from the pension system and an unintended decrease in pre-funding of old-age pensions.