Human Torque teno virus: epidemiology, cell biology and immunology

Torque teno virus (TTV) was discovered in 1997 in the serum of a Japanese patient who had a post-transfusion hepatitis of unknown etiology. It is a small virus containing a circular single-stranded DNA genome which is unique among human viruses. Within a few years after its discovery, the TTVs were noted to form a large family of viruses with numerous genotypes. TTV is highly prevalent among the general population throughout the world, and persistent infections and co-infections with several genotypes occur frequently. However, the pathogenicity and the mechanism for the sustained occurrence of the virus in blood are at present unclear. To determine the prevalence of TTV in Finland, we set up PCR methods and examined the sera of asymptomatic subjects for the presence of TTV DNA and for genotype-6 DNA. TTV was found to be highly prevalent also in Finland; 85% of adults harbored TTV in their blood, and 4% were infected with genotype-6. In addition, TTV DNA was detected in a number of different tissues, with no tissue-type or symptom specificity. Most cell-biological events during TTV infections are at the moment unknown. Replicating TTV DNA has, however, been detected in liver and the hematopoietic compartment, and three mRNAs are known to be generated. To characterize TTV cell biology in more detail, we cloned in full length the genome of TTV genotype 6. We showed that in human kidney-derived cells TTV produces altogether six proteins with distinct subcellular localizations. TTV mRNA transcription was detected in all cell lines transfected with the full-length clone, and TTV DNA replicated in several of them, including those of erythroid, kidney, and hepatic origin. Furthermore, the viral DNA replication was shown to utilize the cellular DNA polymerases. Diagnoses of TTV infections have been based almost solely on PCR, whereas serological tests, measuring antibody responses, would give more information on many aspects of these infections. To investigate the TTV immunology in more detail, we produced all six TTV proteins for use as antigens in serological tests. We detected in human sera IgM and IgG antibodies to occur simultaneously with TTV DNA, and observed appearance of TTV DNA regardless of pre-existing antibodies, and disappearance of TTV DNA after antibody appearance. The genotype-6 nucleotide sequence remained stable for years within the infected subjects, suggesting that some mechanism other than mutations is used by this minute virus to evade our immune system and to establish chronic infections in immunocompetent subjects.

Coastal environmental gradients – Key to reproduction habitat mapping of freshwater fish in the Baltic Sea

Habitat requirements of fish are most strict during the early life stages, and the quality and quantity of reproduction habitats lays the basis for fish production. A considerable number of fish species in the northern Baltic Sea reproduce in the shallow coastal areas, which are also the most heavily exploited parts of the brackish marine area. However, the coastal fish reproduction habitats in the northern Baltic Sea are poorly known. The studies presented in this thesis focused on the influence of environmental conditions on the distribution of coastal reproduction habitats of freshwater fish. They were conducted in vegetated littoral zone along an exposure and salinity gradient extending from the innermost bays to the outer archipelago on the south-western and southern coasts of Finland, in the northern Baltic Sea. Special emphasis was placed on reed-covered Phragmites australis shores, which form a dominant vegetation type in several coastal archipelago areas. The main aims of this research were to (1) develop and test new survey and mapping methods, (2) investigate the environmental requirements that govern the reproduction of freshwater fish in the coastal area and (3) survey, map and model the distribution of the reproduction habitats of pike (Esox lucius) and roach (Rutilus rutilus). The white plate and scoop method with a standardized sampling time and effort was demonstrated to be a functional method for sampling the early life stages of fish in dense vegetation and shallow water. Reed-covered shores were shown to form especially important reproduction habitats for several freshwater fish species, such as pike, roach, other cyprinids and burbot, in the northern Baltic Sea. The reproduction habitats of pike were limited to sheltered reed- and moss-covered shores of the inner and middle archipelago, where suitable zooplankton prey were available and the influence of the open sea was low. The reproduction habitats of roach were even more limited and roach reproduction was successful only in the very sheltered reed-covered shores of the innermost bay areas, where salinity remained low (< 4‰) during the spawning season due to freshwater inflow. After identifying the critical factors restricting the reproduction of pike and roach, the spatial distribution of their reproduction habitats was successfully mapped and modelled along the environmental gradients using only a few environmental predictor variables. Reproduction habitat maps are a valuable tool promoting the sustainable use and management of exploited coastal areas and helping to maintain the sustainability of fish populations. However, the large environmental gradients and the extensiveness of the archipelago zone in the northern Baltic Sea demand an especially high spatial resolution of the coastal predictor variables. Therefore, the current lack of accurate large-scale, high-resolution spatial data gathered at exactly the right time is a considerable limitation for predictive modelling of shallow coastal waters.

Peripheral facial palsy : Grading, Etiology, and Melkersson-Rosenthal Syndrome

The objective of this study was to assess the utility of two subjective facial grading systems, to evaluate the etiologic role of human herpesviruses in peripheral facial palsy (FP), and to explore characteristics of Melkersson-Rosenthal syndrome (MRS). Intrarater repeatability and interrater agreement were assessed for Sunnybrook (SFGS) and House-Brackmann facial grading systems (H-B FGS). Eight video-recorded FP patients were graded in two sittings by 26 doctors. Repeatability for SFGS was from good to excellent and agreement between doctors from moderate to excellent by intraclass correlation coefficient and coefficient of repeatability. For H-B FGS, repeatability was from fair to good and agreement from poor to fair by agreement percentage and kappa coefficients. Because SFGS was at least as good in repeatability as H-B FGS and showed more reliable results in agreement between doctors, we encourage the use of SFGS over H-B FGS. Etiologic role of human herpesviruses in peripheral FP was studied by searching DNA of herpes simplex virus (HSV) -1 and -2, varicella-zoster virus (VZV), human herpesvirus (HHV) -6A, -6B, and -7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by PCR/microarray methods in cerebrospinal fluid (CSF) of 33 peripheral FP patients and 36 controls. Three patients and five controls had HHV-6 or -7 DNA in CSF. No DNA of HSV-1 or -2, VZV, EBV, or CMV was found. Detecting HHV-7 and dual HHV-6A and -6B DNA in CSF of FP patients is intriguing, but does not allow etiologic conclusions as such. These DNA findings in association with FP and the other diseases that they accompanied require further exploration. MRS is classically defined as a triad of recurrent labial or oro-facial edema, recurrent peripheral FP, and plicated tongue. All three signs are present in the minority of patients. Edema-dominated forms are more common in the literature, while MRS with FP has received little attention. The etiology and true incidence of MRS are unknown. Characteristics of MRS were evaluated at the Departments of Otorhinolaryngology and Dermatology focusing on patients with FP. There were 35 MRS patients, 20 with FP and they were mailed a questionnaire (17 answered) and were clinically examined (14 patients). At the Department of Otorhinolaryngology, every MRS patient had FP and half had the triad form of MRS. Two patients, whose tissue biopsies were taken during an acute edema episode, revealed nonnecrotizing granulomatous findings typical for MRS, the other without persisting edema and with symptoms for less than a year. A peripheral blood DNA was searched for gene mutations leading to UNC-93B protein deficiency predisposing to HSV-1 infections; no gene mutations were found. Edema in most MRS FP patients did not dominate the clinical picture, and no progression of the disease was observed, contrary to existing knowledge. At the Department of Dermatology, two patients had triad MRS and 15 had monosymptomatic granulomatous cheilitis with frequent or persistent edema and typical MRS tissue histology. The clinical picture of MRS varied according to the department where the patient was treated. More studies from otorhinolaryngology departments and on patients with FP would clarify the actual incidence and clinical picture of the syndrome.

Water Management in Cambodia Resources and Relations

In Cambodia, water has a special purpose as a source of life and livelihoods. Along with agriculture, fishing and forest use, industry, hydropower, navigation and tourism compete for the water resources. When rights and responsibilities related to essential and movable water are unclear, conflicts emerge easily. Therefore, water management is needed in order to plan and control the use of water resources. The international context is characterized by the Mekong River that flows through six countries. All of the countries by the river have very different roles and interests already depending on their geographical location. At the same time, water is also a tool for cooperation and peace. Locally, the water resources and related livelihoods create base for well-being, for economical and human resources in particular. They in turn are essential for the local people to participate and defend their rights to water use. They also help to construct the resource base of the state administration. Cambodia is highly dependent on the Mekong River. However, Cambodia has a volatile history whose effects can be seen for example in population structure, once suspended public institutions and weakened trust in the society. Relatively stable conditions came to the country as late as in the 1990s, therefore Cambodia for example has a weak status within the Mekong countries. This Master s thesis forms international, national and local interest groups of water use and analyzes their power relations and resources to affect water management. The state is seen as the salient actor as it has the formal responsibility of the water resources and of the coordination between the actions of different levels. In terms of water use this study focuses on production, in management on planning and in power relations on the resources. Water resources of Cambodia are seen consisting of the Mekong River and Tonle Sap Lake and the time span of the study is between the years 1991 and 2006. The material consists of semi-structured interviews collected during summer 2006 in Finland and in Cambodia as well as of literature and earlier studies. The results of the study show that the central state has difficulties to coordinate the actions of different actors because of its resource deficit and internal conflicts. The lessons of history and the vested interests of the actors of the state make it difficult to plan and to strengthen legislation. It seems that the most needed resources at the central state level are intangible as at the village level instead, the tangible resources (fulfilling the basic needs) are primarily important. The local decision-making bodies, NGOs and private sector mainly require legislation and legitimacy to support their role. However, the civil society and the international supporters are active and there are possibilities for new cooperation networks. Keywords: Water management, resources, participation, Cambodia, Mekong

Essays on macroeconomic effects of fiscal policy rules

Economic and Monetary Union can be characterised as a complicated set of legislation and institutions governing monetary and fiscal responsibilities. The measures of fiscal responsibility are to be guided by the Stability and Growth Pact, which sets rules for fiscal policy and makes a discretionary fiscal policy virtually impossible. To analyse the effects of the fiscal and monetary policy mix, we modified the New Keynesian framework to allow for supply effects of fiscal policy. We show that defining a supply-side channel for fiscal policy using an endogenous output gap changes the stabilising properties of monetary policy rules. The stability conditions are affected by fiscal policy, so that the dichotomy between active (passive) monetary policy and passive (active) fiscal policy as stabilising regimes does not hold, and it is possible to have an active monetary - active fiscal policy regime consistent with dynamical stability of the economy. We show that, if we take supply-side effects into ac-count, we get more persistent inflation and output reactions. We also show that the dichotomy does not hold for a variety of different fiscal policy rules based on government debt and budget deficit, using the tax smoothing hypothesis and formulating the tax rules as difference equations. The debt rule with active monetary policy results in indeterminacy, while the deficit rule produces a determinate solution with active monetary policy, even with active fiscal policy. The combination of fiscal requirements in a rule results in cyclical responses to shocks. The amplitude of the cycle is larger with more weight on debt than on deficit. Combining optimised monetary policy with fiscal policy rules means that, under a discretionary monetary policy, the fiscal policy regime affects the size of the inflation bias. We also show that commitment to an optimal monetary policy not only corrects the inflation bias but also increases the persistence of output reactions. With fiscal policy rules based on the deficit we can retain the tax smoothing hypothesis also in a sticky price model.

Lahopuumäärän ennustaminen ja kartoitus lentokonelaserkeilauksen avulla

Lahopuun määrästä ja sijoittumisesta ollaan kiinnostuneita paitsi elinympäristöjen monimuotoisuuden, myös ilmakehän hiilen varastoinnin kannalta. Tutkimuksen tavoitteena oli kehittää aluepohjainen laserkeilausdataa hyödyntävä malli lahopuukohteiden paikantamiseksi ja lahopuun määrän estimoimiseksi. Samalla tutkittiin mallin selityskyvyn muuttumista mallinnettavan ruudun kokoa suurennettaessa. Tutkimusalue sijaitsi Itä-Suomessa Sonkajärvellä ja koostui pääasiassa nuorista hoidetuista talousmetsistä. Tutkimuksessa käytettiin harvapulssista laserkeilausdataa sekä kaistoittain mitattua maastodataa kuolleesta puuaineksesta. Aineisto jaettiin siten, että neljäsosa datasta oli käytössä mallinnusta varten ja loput varattiin valmiiden mallien testaamiseen. Lahopuun mallintamisessa käytettiin sekä parametrista että ei-parametrista mallinnusmenetelmää. Logistisen regression avulla erikokoisille (0,04, 0,20, 0,32, 0,52 ja 1,00 ha) ruuduille ennustettiin todennäköisyys lahopuun esiintymiselle. Muodostettujen mallien selittävät muuttujat valittiin 80 laserpiirteen ja näiden muunnoksien joukosta. Mallien selittävät muuttujat valittiin kolmessa vaiheessa. Aluksi muuttujia tarkasteltiin visuaalisesti kuvaamalla ne lahopuumäärän suhteen. Ensimmäisessä vaiheessa sopivimmiksi arvioitujen muuttujien selityskykyä testattiin mallinnuksen toisessa vaiheessa yhden muuttujan mallien avulla. Lopullisessa usean muuttujan mallissa selittävien muuttujien kriteerinä oli tilastollinen merkitsevyys 5 % riskitasolla. 0,20 hehtaarin ruutukoolle luotu malli parametrisoitiin muun kokoisille ruuduille. Logistisella regressiolla toteutetun parametrisen mallintamisen lisäksi, 0,04 ja 1,0 hehtaarin ruutukokojen aineistot luokiteltiin ei-parametrisen CART-mallinnuksen (Classification and Regression Trees) avulla. CARTmenetelmällä etsittiin aineistosta vaikeasti havaittavia epälineaarisia riippuvuuksia laserpiirteiden ja lahopuumäärän välillä. CART-luokittelu tehtiin sekä lahopuustoisuuden että lahopuutilavuuden suhteen. CART-luokituksella päästiin logistista regressiota parempiin tuloksiin ruutujen luokituksessa lahopuustoisuuden suhteen. Logistisella mallilla tehty luokitus parani ruutukoon suurentuessa 0,04 ha:sta(kappa 0,19) 0,32 ha:iin asti (kappa 0,38). 0,52 ha:n ruutukoolla luokituksen kappa-arvo kääntyi laskuun (kappa 0,32) ja laski edelleen hehtaarin ruutukokoon saakka (kappa 0,26). CART-luokitus parani ruutukoon kasvaessa. Luokitustulokset olivat logistista mallinnusta parempia sekä 0,04 ha:n (kappa 0,24) että 1,0 ha:n (kappa 0,52) ruutukoolla. CART-malleilla määritettyjen ruutukohtaisten lahopuutilavuuksien suhteellinen RMSE pieneni ruutukoon kasvaessa. 0,04 hehtaarin ruutukoolla koko aineiston lahopuumäärän suhteellinen RMSE oli 197,1 %, kun hehtaarin ruutukoolla vastaava luku oli 120,3 %. Tämän tutkimuksen tulosten perusteella voidaan todeta, että maastossa mitatun lahopuumäärän ja tutkimuksessa käytettyjen laserpiirteiden yhteys on pienellä ruutukoolla hyvin heikko, mutta vahvistuu hieman ruutukoon kasvaessa. Kun mallinnuksessa käytetty ruutukoko kasvaa, pienialaisten lahopuukeskittymien havaitseminen kuitenkin vaikeutuu. Tutkimuksessa kohteen lahopuustoisuus pystyttiin kartoittamaan kohtuullisesti suurella ruutukoolla, mutta pienialaisten kohteiden kartoittaminen ei onnistunut käytetyillä menetelmillä. Pienialaisten kohteiden paikantaminen laserkeilauksen avulla edellyttää jatkotutkimusta erityisesti tiheäpulssisen laserdatan käytöstä lahopuuinventoinneissa.