Molecular pathogenesis of human parechovirus 1 infection

The Parechoviruses (HPEV) belong to the family Picornaviridae of positive-stranded RNA viruses. Although the parechovirus genome shares the general properties of other picornaviruses, the genus has several unique features when compared to other family members. We found that HPEV1 attaches to αv integrins on the cell surface and is internalized through the clathrin-mediated endocytic pathway. During he course of the infection, the Golgi was found to disintegrate and the ER membranes to swell and loose their ribosomes. The replication of HPEV1 was found to take place on small clusters of vesicles which contained the trans-Golgi marker GalT as well as the viral non-structural 2C protein. 2C was additionally found on stretches of modified ER-membranes, seemingly not involved in RNA replication. The viral non-structural 2A and 2C proteins were studied in further detail and were found to display several interesting features. The 2A protein was found to be a RNA-binding protein that preferably binds to positive sense 3 UTR RNA. It was found to bind also duplex RNA containing 3 UTR(+)-3 UTR(-), but not other dsRNA molecules studied. Mutagenesis revealed that the N-terminal basic-rich region as well as the C-terminus, are important for RNA-binding. The 2C protein on the other hand, was found to have both ATP-diphosphohydrolase and AMP kinase activities. Neither dATP nor other NTP:s were suitable substrates. Furthermore, we found that as a result of theses activities the protein is autophosphorylated. The intracellular changes brought about by the individual HPEV1 non-structural proteins were studied through the expression of fusion proteins. None of the proteins expressed were able to induce membrane changes similar to those seen during HPEV1 infection. However, the 2C protein, which could be found on the surface of lipid droplets but also on diverse intracellular membranes, was partly relocated to viral replication complexes in transfected, superinfected cells. Although Golgi to ER traffic was arrested in HPEV1-infected cells, none of the individually expressed non-structural proteins had any visible effect on the anterograde membrane traffic. Our results suggest that the HPEV1 replication strategy is different from that of many other picornaviruses. Furthermore, this study shows how relatively small differences in genome sequence result in very different intracellular pathology.

Vaggvisor i Kvevlax : Språkliga strukturer och konstruktioner

Lullabies in Kvevlax. Linguistic structures and constructions. The study is a linguistic analysis of constructions that shape the texts used in lullabies in Kvevlax in Ostrobothnia in Finland. The empirical goal is to identify linguistic constructions in traditional lullabies that make use of the dialect of the region. The theoretical goal was to test the usability of Construction Grammar (CxG) in analyses of this type of material, and to further develop the formal description of Construction Grammar in such a way as to make it possible to analyze all kinds of linguistically complex texts. The material that I collected in the 1960s comprises approximately 600 lullabies and concomitant interviews with the singers on the use of lullabies. In 1991 I collected additional material in Kvevlax. The number of informants is close to 250. Supplementary material covering the Swedish-language regions in Finland was compiled from the archives of the Society of Swedish Literature in Finland. The first part of the study is mainly based on traditional grammar and gives general information about the language and the structures used in the lullabies. In the detailed study of the Kvevlax lullabies in the latter part of the study I use a version of Construction Grammar intended for the linguistic analysis of usage-based texts. The analysis focuses on the most salient constructions in the lullabies. The study shows that Construction Grammar as a method has more general applicability than traditional linguistic methods. The study identifies important constructions, including elements typical of this genre, that structure the text in different variants of the same lullabies. In addition, CxG made it possible to study pragmatic aspects of the interactional, cultural and contextual language that is used in communication with small children. The constructions found in lullabies are also used in language in general. In addition to being able to give detailed linguistic descriptions of the texts, Construction Grammar can also explain the multidimensionality of language and the variations in the texts. The use of CxG made it possible to show that variations are not random but follow prototypical linguistic patterns, constructions. Constructions are thus found to be linguistic resources with built-in variation potentials.

Diabetesassocierade autoantikroppar hos barn med nydiagnostiserad typ 1 diabetes i relation till demografiska och kliniska faktorer

Syftet med studien var att undersöka sambanden mellan de diabetesassocierade autoantikropparna ICA, IAA, GADA, IA-2A och klinisk manifestation, HLA-genotyp, släktanamnes samt demografiska faktorer såsom ålder och kön hos finländska barn under 15 år med nydiagnostiserad typ 1 diabetes. Analyserna baserades på ett utdrag ur det finländska pediatriska diabetesregistret (2257 barn). Antikroppsfrekvenserna fastställdes utgående från halterna i serum. Alla barn HLA-genotypades och indelades i DR3- och DR4-positiva. Småbarnen (?5 år) hade ofta 3-4 positiva antikroppar. Äldre barn hade färre autoantikroppar men en allvarligare metabolisk dekompensering vid diagnostillfället. Diabetisk ketoacidos var vanligare hos flickor. I gruppen med endast en positiv autoantikropp var IA-2A-barnen oftare acidotiska, i övrigt påverkade inte antikroppsprofilen den kliniska bilden. Högriskgenotypen DR4/non-DR3 var associerad med IA-2A, som verkar fungera som en markör för betacelldestruktion. Det omfattande patientmaterialet gav stöd åt tidigare rapporter om samband mellan autoantikroppar och ålder, kön samt genotyp. Den allvarligare metaboliska dekompenseringen hos äldre barn tyder på att de inte diagnostiseras lika snabbt som småbarn.

Very Low Birth Weight Infants as Young Adults : Focus on aspects of cognition, behavior and sleep

Major advances in the treatment of preterm infants have occurred during the last three decades. Survival rates have increased, and the first generations of preterm infants born at very low birth weight (VLBW; less than 1500 g) who profited from modern neonatal intensive care are now in young adulthood. The literature shows that VLBW children achieve on average lower scores on cognitive tests, even after exclusion of individuals with obvious neurosensory deficits. Evidence also exists for an increased risk in VLBW children for various neuropsychiatric disorders such as attention-deficit hyperactivity disorder (ADHD) and related behavioral symptoms. Up till now, studies extending into adulthood are sparse, and it remains to be seen whether these problems persist into adulthood. The aim of this thesis was to study ADHD-related symptoms and cognitive and executive functioning in young adults born at VLBW. In addition, we aimed to study sleep disturbances, known to adversely affect both cognition and attention. We hypothesized that preterm birth at VLBW interferes with early brain development in a way that alters the neuropsychological phenotype; this may manifest itself as ADHD symptoms and impaired cognitive abilities in young adulthood. In this cohort study from a geographically defined region, we studied 166 VLBW adults and 172 term-born controls born from 1978 through 1985. At ages 18 to 27 years, the study participants took part in a clinic study during which their physical and psychological health was assessed in detail. Three years later, 213 of these individuals participated in a follow-up. The current study is part of a larger research project (The Helsinki Study of Very Low Birth Weight Adults), and the measurements of interest for this particular study include the following: 1) The Adult Problem Questionnaire (APQ), a self-rating scale of ADHD-related symptoms in adults; 2) A computerized cognitive test battery designed for population studies (CogState®) which measures core cognitive abilities such as reaction time, working memory, and visual learning; 3) Sleep assessment by actigraphy, the Basic Nordic Sleep Questionnaire, and the Morningness-Eveningness Questionnaire. Actigraphs are wrist-worn accelerometers that separate sleep from wakefulness by registering body movements. Contrary to expectations, VLBW adults as a group reported no more ADHD-related behavioral symptoms than did controls. Further subdivision of the VLBW group into SGA (small for gestational age) and AGA (appropriate for gestational age) subgroups, however, revealed more symptoms on ADHD subscales pertaining to executive dysfunction and emotional instability among those born SGA. Thus, it seems that intrauterine growth retardation (for which SGA served as a proxy) is a more essential predictor for self-perceived ADHD symptoms in adulthood than is VLBW birth as such. In line with observations from other cohorts, the VLBW adults reported less risk-taking behavior in terms of substance use (alcohol, smoking, and recreational drugs), a finding reassuring for the VLBW individuals and their families. On the cognitive test, VLBW adults free from neurosensory deficits had longer reaction times than did term-born peers on all tasks included in the test battery, and lower accuracy on the learning task, with no discernible effect of SGA status over and above the effect of VLBW. Altogether, on a group level, even high-functioning VLBW adults show subtle deficits in psychomotor processing speed, visual working memory, and learning abilities. The sleep studies provided no evidence for differences in sleep quality or duration between the two groups. The VLBW adults were, however, at more than two-fold higher risk for sleep-disordered breathing (in terms of chronic snoring). Given the link between sleep-disordered breathing and health sequelae, these results suggest that VLBW individuals may benefit from an increased awareness among clinicians of this potential problem area. An unexpected finding from the sleep studies was the suggestion of an advanced sleep phase: The VLBW adults went to bed earlier according to the actigraphy registrations and also reported earlier wake-up times on the questionnaire. In further study of this issue in conjunction with the follow-up three years later, the VLBW group reported higher levels of morningness propensity, further corroborating the preliminary findings of an advanced sleep phase. Although the clinical implications are not entirely clear, the issue may be worth further study, since circadian rhythms are closely related to health and well-being. In sum, we believe that increased understanding of long-term outcomes after VLBW, and identification of areas and subgroups that are particularly vulnerable, will allow earlier recognition of potential problems and ultimately lead to improved prevention strategies.

Samarbete mellan konkurrenter - en undersökning av österbottniska sm-företag

Under senare tid har förekomsten av samarbete mellan konkurrerande sm-företag ökat. Forskningen kring ämnet har dock bedrivits i mindre skala, framför allt om man beaktar finländska (nordiska) förhållanden. Syftet med denna undersökning är att kartlägga förekomsten av samarbete mellan konkurrerande sm-företag i Österbotten (Finland), samt beskriva dessa. Gällande demografiska variabler jämförs dessa företag även med sm-företag som inte samarbetar. Data insamlades genom en enkät utskickad i november 2001 till 345 sm-företag i Österbotten. Svarsprocenten var 35.1. Av de respondenter som besvarade enkäten, var 47.9 procent involverade i ett eller flera samarbeten med ett eller flera företag som var deras konkurrenter. Samarbete mellan konkurrenter är således inte ett ovanligt fenomen, utan innefattar allt från informella, operativa samarbeten till formella, strategiskt viktiga samarbeten. Samarbete inom produktion var den mest vanligt förekommande formen av samarbete. Partnern kom från Finland, även om målmarknaderna för samarbetet fanns både i Finland och i utlandet. Denna undersökning kunde inte identifiera någon större skillnad mellan de sm-företag som samarbetade med konkurrenter och de sm-företag som inte samarbetade. Det intressanta är således att det inte verkar finnas några skillnader vad gäller ålder, omsättning, omsättningsökning, underleverans- och exportverksamhet mellan de samarbetande och de icke samarbetande företagen. Skillnaderna bör således sökas i andra variabler. Den enda signifikanta skillnaden kunde upptäckas i upplevelsen av konkurrens. Tidigare forskning har identifierat att osäkerhet i konkurrensen är ett incitament till att börja samarbeta med konkurrenter. Denna undersökning förstärker detta antagande. De samarbetande företagen upplevde att konkurrensen var hårdare än de icke samarbetande företagen. Bland de samarbetande företagen var det speciellt de mindre (med en personalstyrka mellan 10 och 50 arbetstagare) som upplevde att konkurrensen var hård. Undersökningen har finansierats med stipendiemedel från Sparbanksstiftelsen i Vasa och Handlande Gustav Svanljungs fond.

En förutbestämd sanning : Barnamord och delaktighet i 1700-talets Finland belysta genom kön, kropp och social kontroll

The study analyses the prevention or endorsing of the crime of infanticide in Finland 1702 1807, rather than the result. Also the impacts of the female body, biology of childbirth and experiences of pregnancy are examined, together with insights from modern medical research. Circumstances are reconstructed by a critical reading of judicial records on all levels of the judicial system. In all 269 cases of infanticide and 142 accessory crimes within the jurisdiction of the Turku court of appeal are studied, with particular focus on exceptionally well recorded cases of 83 accused women and 41 women and men accused of being party to the crime. Secondary sources are medical and jurisprudential writings, the public debate on infanticide, broadsheets and letters asking the King for pardon. Infanticide was considered murder by law. Unmarried women were predetermined as the main culprits. Nevertheless, deliberate infanticides were rare and committed mostly in accomplice. The majority of the infanticides studied were cases where inexperienced and unmarried women accidentally had given birth alone and usually to a dead child. Unaware that the pain they were experiencing was in fact a labour, the accused women instinctively sought solitude to push out the child. Some misunderstood the birth as an urgent need to defecate. The unexpected delivery ended in hiding the baby without remorse. This crime was promoted by several factors in Finnish rural culture, amongst others that also married women hid their pregnancy. The immediate household members did not necessarily know about the childbirth and failed to help the woman. This typical pattern in most cases of infanticide in 18th century Finland is also recorded in modern cases of unknown pregnancies. Fear of accountability prevented witnesses testifying to the actual course of events. The truth remained elusive. With only a few exceptions, the women were sentenced to death or imprisonment. The majority of those accused of accomplice were acquitted. However, too harsh sentences for accidents affected the reporting of the crime. Criminal politics failed to curtail infanticide as the crime was unsatisfactorily addressed by law, society and the judicial system.

Vapaata mielenjuoksua : Suomenkielisen freestyle-rapin ilmenemismuodot, estetiikka ja kompositio

The thesis is about Finnish freestyle-rap, a modern form of oral poetry producing improvised rap lyrics at the moment of performance. The research material consists of interviews with seven freestyle experts and a DVD from Finnish Rap Championships 2005 containing freestyle-rap. The thesis has three goals: describing the different variations or subgenres of freestyle, outlining the esthetics and register of freestyle, and examining the composition of freestyle. The research material acts a central role in the thesis but the theoretical framework is also wide: cornerstones are John Miles Foley's register analysis, oral formulaic theory and William Levelt's psycholinguistic theory on planning of speech. Freestyle is divided into three partially overlapping genres with slight variation in conventions. The genres are freestyle battle, cypher, and live freestyle. Freestyle's esthetics are composed of certain qualities and preferences: the rhyme is a syllabically repeating vocal rhyme. The rapping must be synchronised with the background rhythm and the rhyme comes in the end of the line. The lyrics must be somehow anchored to the surroundings and the moment of performance. The style of rapping, ie. flow, has to be personal one way or the other. Individual formulas are used to some extent in freestyle compostition. When planning the lines, all other content is subordinate to the rhyme, whose phonetic processing is the primary act in the planning of freestyle. This discovery sets Levelt's theory open to doubt.

Betydelser i barnfamiljsbroschyrer : Systemisk-funktionell analys av den tänkta läsaren och institutionen

This thesis concerns Swedish and Finland-Swedish brochures to families with children, presenting family allowances from the social insurance institutions in the two countries. The aim of the study is to analyse what meanings are conveyed with reference to the conceivable reader and the institution in the brochures. The material consists of information brochures in Swedish from Kela, the social insurance institution of Finland, and Försäkringskassan, the Swedish social insurance agency, issued during 2003–2006. The general theoretical framework is systemic-functional linguistics (SFL) as presented by Halliday & Matthiessen (2004) and Holmberg & Karlsson (2006). The study consists of a quantitative study of the lexical choices of the social insurance brochures. Furthermore, a qualitative process and participant analysis is annotated with the UAM Corpus tool and the results are quantified. Speech functions and modal auxiliaries are analysed qualitatively. The analysis shows that material and relational processes are most common. The relational and verbal processes are used more in the Sweden-Swedish brochures, while the material processes are more common in the Finland-Swedish brochures. The participants in the brochures are the institution, mentioned by its name, and the conceivable reader, directly addressed with “you” (du). In addition, the referent “child” is often mentioned. The participants assigned for the reader are Actor, Receiver, Carrier and Speaker. In the Finland-Swedish texts, the reader is often an Actor, while the reader in the Sweden-Swedish texts is a Carrier. Thus, the conceivable reader is an active participant who takes care of his or her own matters using the internet, communicates actively to the institution and has legal rights and obligations. The institution is visible in the texts but does not have an active role as the name of the institution is mostly used in circumstances. The institution is not often a participant, but when it is, it is Actor, Receiver, Listener and Carrier, expecting the clients to address it. Speech functions are performed in different ways. For instance, questions structure the reading process and commands are realised by modal auxiliaries, not by imperatives. The most common modal auxiliary is kan (can, may), and another common auxiliary is ska (shall, must). Statements are surrounded by subordinate clauses and adverbs that describe situations and criteria. The results of the study suggest that the brochures in the two countries are similar, in particular when produced in similar ways, that is, when the Finland-Swedish texts are not translated. Existing differences reflect the differences in the institutions, the social insurance systems and the cultural contexts. KEYWORDS: Finland-Swedish, Swedish, comparative analysis, SFL, discourse analysis, administrative language, institutional discourse, institutional communication