Matti Laurila : Jääkäriupseeri, suojeluskuntapäällikkö, rintamakomentaja

Matti Laurila (1895 1983) This is a biographical research of a Jaeger officer, a Civil Guard Chief, a Field Commander Matti Laurila. A broader practice of qualitative methods was utilized in the research. The main aim is a permanent reconstruction and reinterpretation of past events through the experiences of the study object. The life and times of Laurila are intertwined with the crucial events that led to the Finnish Declaration of Independence. Afterwards he helped to ensure that the young republic also stayed independent. As a Jaeger in the winter of 1917 Laurila witnessed an incident he would never forget. After disobeying a direct order, Sven Saarikoski from Lapua was shot dead by his commanding officer, K. A. Ståhlberg, on the ice of the river Aa. Laurila faced the horrors of war at closer quarters, for he lost his father and his brother in the battle of Länkipohja on 16th March 1918. This battle was a major turning point for Laurila and profoundly influenced the rest of his life. The relationship between Laurila and his superiors was problematic almost throughout his military career, haunted as he was by the memory of Sven Saarikoski's execution and the losses in Länkipohja The position of Laurila as an authority in South Ostrobothnia was a key factor in preventing the extreme right from rallying enough Civil Guard troops to escalate the embryonic Mäntsälä rebellion of 1932. After the rebellion Laurila routinely opposed anything he saw as a threat to the independence of the Civil Guard. He would flatly refuse to even consider the integration of the Civil Guard into the national defence force. His uncompromising stand in this matter annoyed some among the higher ranking officers. After the Winter War Laurila got himself into a dispute with Jaeger Colonel H. E. Hannuksela that would have long-lasting consequences. The conflicts between them became widely known in the attack phase of the Continuation War in 1941 at the latest. Laurila had to give up his military career at the end of 1944. In the years that followed he did what he could to ensure that the South Ostrobothnia Civil Guard patrimony remained in the province. Laurila's position as a respected authority in South Ostrobothnia remained unchanged until his death.

Ajatuksista operaatioiksi : Suomen armeijan hyökkäysoperaatioiden suunnittelu jatkosodassa

In the research on the Continuation War, interest in the events themselves had exceeded the interest in military planning. Careful consideration has not been given to the planning process and the options that were available. This study shows how the planning of these operations was carried out and identifies the persons responsible. Contrary to earlier research this study shows that persons other than Field-Marshal Carl Gustaf Mannerheim and Quartermaster-General Aksel Airo took part in the planning. Furthermore, the plan was to carry out the operations further east than was ultimately done. The operation plans were coordinated by the Operations Department of Headquarters, which had the opportunity to influence on both Mannerheim and Airo. Part of the actual planning was made outside Headquarters, but final decisions were taken at Headquarters. It is worth observing that many times Mannerheim asked President Risto Ryti for his opinion concerning these operations. The Germans tried to influence the Finnish plans, but the Finns took their decisions independently, although they took German requests into account. It is well-known that the attack by the Finnish forces was stopped at the end of the year 1941. It is less well-known that the Finns planned new attacks until the autumn of 1942. At that point the Finns were convinced that the Germans would lose the war. The Finns were thus prepared to keep advancing should the Germans progress in the direction of Leningrad. This study shows that the Finnish military leaders worked for Finland s own plans and their cooperation with the Germans was directed to achieving this goal. In other words, Finland tried expand eastward with the help of the Germans. This purpose was particularly evident in the planning of the operations in the Hanko district and the Karelian Isthmus in the summer and autumn of 1941, in the Sorokka district in the spring of 1942 and around Lake Ladoga in the summer and autumn of 1942. The Finns reduced their activities when Germans took over responsibility for the operations. However, at the same time the Finns tried to support Germans in passive ways. The Finns justified the decrease in their activities with lack of Finnish forces and numerous defeats. Earlier research has shown that Finland was an active operator in the Continuation War and tried to take back the areas lost in the Winter War. In this study that view becomes more precise and clear especially with regard to Field-Marshal Mannerheim and other high military leaders. There is clear indication that the Finns would have attacked much further east had a German success made such an attack possible.

Finnish Homicides and Mental Disorders: An investigation of offense and offender characteristics

Although the majority of people with mental illness are not violent, scientific studies over the last decades show that certain psychiatric disorders increase the risk of violent behavior, including homicide. This thesis examined crime scene behaviors and offender background characteristics among mentally ill Finnish homicide offenders. Previously, homicide crime scene behaviors have been investigated in relation to offender demographic characteristics, whereas this study compares the behaviors of offenders with various mental illnesses. The study design was a retrospective chart review of the forensic psychiatric statements of Finnish homicide offenders. The work consists of four substudies. The aims of the study were as follows: To describe differences in the childhood and family backgrounds as well as in the adolescent and adult adjustment of Finnish homicide offenders belonging to different diagnostic categories (schizophrenia, personality disorder, alcoholism, drug addiction or no diagnosis). Further, the study examined associations between the crime scene behaviors and mental status of these offenders. Also, the distinguishing characteristics between two groups of offenders with schizophrenia were examined: early starters, who present antisocial behavior before the onset of schizophrenia, and late starters, who first offend after the onset of mental disorder. Finally, it was investigated how the use of excessive violence is associated with clinical and circumstantial variables as well as offender background characteristics among homicide offenders with schizophrenia. The main findings of the study can be summarized as follows. First, offenders with personality disorder or drug addiction had experienced multiple difficulties in their early environments: both family and individual problems were typical. Offenders with schizophrenia were relatively well-adjusted in childhood compared to the other groups. However, in adolescence and adulthood, social isolation, withdrawal and other difficulties attributable to these offenders illness became evident. In several aspects, offenders with alcohol dependency resembled offenders with no diagnosis in that these offenders had less problematic backgrounds compared to other groups. Second, the results showed that crime scene behaviors, victim gender and the victim-offender relationship differ between the groups. In particular, offenders with a diagnosis of schizophrenia or drug addiction have some unique features in their crime scene behaviors and choice of victims. Offenders with schizophrenia were more likely to kill a blood relative, to use a sharp weapon and to injure the victim s face. Drug addiction was associated with stealing from the victim and trying to cover up the body. Third, the results suggest that the offense characteristics of early- and late-start offenders with schizophrenia differ only modestly. However, several significant differences between the groups were found in characteristics of offenders: early starters had experienced a multitude of problems in their childhood surroundings and also later in life. Fourth, violent acts where the offender did not commit the offense alone or had previous homicidal history were predictive of excessive violence among offenders with schizophrenia. Positive psychotic symptoms did not predict the use of excessive violence. Nearly one third of the cases in the sample involved multiple and severe violence, including features such as sadism, mutilation, sexual components or extreme stabbing. In sum, mentally disordered homicide offenders are heterogeneous in their offense characteristics as well as their background characteristics. Empirically based information on how the offender s mental state is associated with specific crime scene behaviors can be utilized within the police force in developing methods of prioritizing suspects in unsolved homicide cases. Also, these results emphasise the importance of early interventions for problem families and children at risk of antisocial behavior. They may also contribute to the development of effective treatment for violent offenders.

Aza-Wittigringslutningar vid syntes av sammansmälta kväveheterocykler

Denna pro gradu avhandling är en litteraturstudie av intramolekylära aza-Wittigringslutningar vid syntes av sammansmälta kväveheterocykler. I arbetet behandlas material huvudsakligen från 1980 och framöver. Aza-Wittigreaktionen påminner om den analoga Wittigreaktionen. Aza-Wittigreaktioner har nästan uteslutande gjorts mellan karbonylgrupper och iminofosforaner. Reaktionsmekanismen sker enligt en tvåstegsaddition, som inleds av iminokvävets nukleofila attack till karbonylkolet och avslutas av att en zwitterjonisk betain bildar en azoxafosfetanintermediär. Intermediären sönderfaller spontant till en iminoprodukt och fosfinoxid. Reaktionen görs ofta under milda betingelser d.v.s. vid rumstemperatur och dessutom utan dyr arbetsutrustning Ett vanligt sätt att framställa iminofosforanen är från azid genom Staudingerreaktion och ofta kombineras Staudinger- och aza-Wittigreaktionerna så att iminofosforanen inte isoleras före ringslutningen. Alla andra ringslutningsreaktioner än aza-Wittig, såsom elektrocykliska ringslutningar, har uteslutits ur detta arbete. Materialet i litteraturstudien har indelats enligt vilken typ av karbonylgrupp iminofosforanen reagerar med. På så vis åskådliggörs hurudana typiska produktmolekyler som erhållits med ringslutning till en viss typ av karbonylgrupp. Det har visat sig att det är förmånligt om karbonylkolet har elektronunderskott och iminofosforanens kväve har elektronöverskott. Den ringslutande molekylens entropi och närbelägna substituenters elektroniska och steriska natur samt produktmolekylens termodynamiska fördelaktighet inverkar tillsammans på reaktionens gång. Ifall reaktionen förväntas ske långsamt är det bättre att använda sig av alkyliminofosforaner än aryliminofosforaner. Valet av lösningsmedel har nästan uteslutande lämnats oförklarat i de behandlade publikationerna men i de flesta fall har ortoxylen eller toluen varit goda lösningsmedel. Oönskad tetrazolbildning av aziden kan minimeras genom användning av opolärt lösningsmedel. Likaså kan förmånligt placerade kväveskyddsgrupper hindra intramolekylära vätebindningar. På senare tid har aza-Wittigreaktionen allt mera tillämpats vid framställning av farmakologiska produkter, vilket ökat intresset för att framställa stora mängder närbesläktade produktmolekyler. Dylika molekylbibliotek har med fördel framställts i fastfas varvid reningen av produkten underlättats märkbart. Ett nytt område inom aza-Wittigsyntetiken är asymmetriska reaktioner, vilka säkert kommer att få mera uppmärksamhet i framtiden. I denna litteraturstudie framkom det att många av de utförda synteserna på området kunde upprepas med större variation och systematik gällande reagens och reaktionsbetingelser.

Responses of Scots pine to nickel and copper exposure and herbivory

The goal of this thesis was to examine the ecophysiological responses of Scots pine (Pinus sylvestris L.), with an emphasis on the oxidative enzyme peroxidase and plant phenolics to environmental stresses like elevated levels of nickel (Ni) and copper (Cu), and herbivory. The effects of Ni and Cu were studied in a gradient survey at a sulphur dioxide contaminated site in the Kola Peninsula, and with experiments in which seedlings were exposed to Ni mist or to Ni and Cu amended into the soil. In addition, experimental Ni exposure was combined with disturbance of the natural lichen cover of the forest ground layer. Pine sawfly attack was simulated in the early season defoliation experiment, in which mature Scots pine were defoliated (100 %) during two successive years in a dry, nutrient-poor Scots pine stand. In addition, the effect of previous defoliation on the growth of sawfly (Diprion pini L.) larvae was studied. Apoplastic peroxidase activity was elevated in the needles of pine in a Ni- , Cu- and SO2- polluted environment, which indicated an increased oxidative stress. Increased foliar peroxidase activity due to Ni contamination was shown in the experiment, in which Ni was added as mist. No such response was found in peroxidase acitivity of the roots exposed to elevated Ni and/or Cu in the soil. Elevated Ni in the soil increased the concentration of foliar condensed tannins, which are able to bind heavy metals in the cells. Addition of low levels of Ni in the soil appeared to benefit pine seedlings, which was seen as promoted shoot growth and better condition of the roots. Wet Ni deposition of 2000 mg m-2 reduced growth and survival of pine seedlings, whereas deposition levels 200 mg m-2 or 20 mg m-2 caused no effects in a 2-y lasting experiment. The lichen mat on the forest floor did not act as an effective buffer against the adverse impacts of heavy metals on pine seedlings. However, some evidence was found indicating that soil microbes profited from the lichen mat. Artificial defoliation increased peroxidase activity in the Scots pine needles. In addition, defoliation decreased nitrogen, diamine putrescine and glucose concentrations in the needles and increased the concentrations of several phenolic compounds, starch and sucrose. Previous artificial defoliation led to poor growth of sawfly larvae reared on the pines, suggesting delayed induced resistance in Scots pine. However, there was no consistent relationship between inducibility (proportional increase in a compound following defoliation) and adverse effects on the growth of pine sawfly larvae. The observed inducible responses in needle phenolics due to previous defoliation thus appear to represent non-specific responses against sawflies.

The effects of eutrophication on alternative reproductive tactics in threespine sticklebacks

When organisms compete for mates and fertilisations, the process of sexual selection drives the evolution of traits that increase reproductive success. The traits targeted by selection, and the extent to which they change, are constrained by the local environment. Sexual selection due to female mate choice can be undermined by alternative reproductive tactics (ARTs), which refers to discontinuous variation in traits or behaviours used in reproduction. As human activities are rapidly changing our planet, this raises the question how ARTs will be affected. Fish show a bewildering diversity of ARTs, which make them good model organisms to answer these questions. One example of human-induced environmental change, which is affecting aquatic ecosystems around the world, is eutrophication, the over-enrichment of water bodies with nutrients. One of its effects is decreased underwater visibility due to increases in both turbidity and vegetation density. The aims of this thesis were to investigate the effects increased turbidity and vegetation density have on an ART in sticklebacks, a fish common to marine and fresh water bodies of the Northern hemisphere. I furthermore investigated how this affected sexual selection for male size, a trait commonly under selection. I used a combination of behavioural observations in microcosms, where I manipulated underwater visibility, with collection of genetic material to reconstruct parentage of broods, and thus identify sneak fertilisations. The results show that turbidity might have weak negative effects on the frequency of sneaking behaviour, although this behaviour was rather infrequent in these experiments, which complicates firm conclusions. In dense vegetation the number of sneak fertilisations decreased slightly, as fewer nesting males sneaked, while the number of non-nesting males sneaking remained constant. The paternity analyses revealed that a significantly smaller fraction of eggs was sneak fertilised under dense vegetation. Furthermore, amongst the nesting males that sneaked, the amount of eggs sneak fertilised correlated positively with courtship success. A reduction in sneaking by these males under dense vegetation equalised the distribution of fertilisation success, in turn contributing to a decrease in the opportunity for selection. Under dense vegetation significantly more males built nests, which has also been observed in previous field studies. In a separate experiment we addressed if such changes in the proportion of nesters and non-nesters, without changes in visibility, affected the incidence of sneak fertilisation. My results show this was not the case, likely because sneaking is an opportunistic tactic shown by both nesters and non-nesters. Non-nesters did sneak proportionately more when there were many of them, which could be due to changes in the cost-benefit ratio of sneaking. As nesters can only attack one intruder at a time, the costs and risks per sneaker will decrease as the number of sneakers increases. The defensive behaviours shown by the nesters before spawning shifted to a more aggressive form of nest defence. This could be because less aggressive behaviours lose their effectiveness when the number of intruders increases. It could also indicate that the risks associated with aggressive behaviours decrease when there are fewer fellow nesters, as other studies indicate nesters are competitive and aggressive individuals. Under turbid conditions I did not detect changes in the opportunity for selection, based on fertilisation success, nor was male size under significant selection under clear or turbid conditions. More thorough analyses under densely vegetated conditions across the nesting, courtship and fertilisation stages revealed a decrease in the opportunity for selection across all stages. A reduction in sneaking by nesters contributed to this. During the nesting stage, but not during later stages, body size was under significant directional selection under sparse, but not dense vegetation. This illustrates the importance of considering all selection stages to get a complete picture of how environmental changes affect sexual selection. Leaving out certain stages or subgroups can result in incomplete or misleading results.

Study of sleep and evaluation of sumatriptan and rizatriptan in the acute treatment of migraine in children and adolescents

Migraine is a common disease in children and adolescents, affecting roughly 10% of school-aged children. Recent studies have revealed an increasing incidence of childhood migraine, but migraine remains an underrecognized and undertreated condition in the pediatric population. Migraine attacks are painful and disabling and can affect a child´s life in many ways. Effective drug treatment is usually needed. The new migraine drugs, triptans, were introduced at the beginning of the 1990s and have since been shown to be very effective in the treatment of migraine attacks in adults. Although they are widely used in adults, the acute treatment of migraine in children and adolescents is still based on paracetamol and nonsteroidal anti-inflammatory drugs. Some children can control their attacks satisfactorily with simple analgesics, but at least one-third need more powerful treatments. When this thesis work commenced, hardly any information existed on the efficacy and safety of triptans in children. The study aim of the thesis was to identify more efficient treatments of migraine for children and adolescents by investigating the efficacy of sumatriptan nasal spray and oral rizatriptan compared with placebo in them. Sleep has an impact on migraine in many aspects. Despite the clinical relevance and common manifestation of sleep in the context of migraine in children, very little research data on the true frequency of sleep exist. As sleeping is so often related to childhood migraine, it can be a confounding factor in clinical drug trials of migraine treatments in children and adolescents. How the results of a sleeping child should be analyzed is under continual debate. The aim of the thesis was also to clarify this as well as to evaluate the frequency of sleeping during migraine attacks in children and factors affecting frequency. Both nasal sumatriptan and oral rizatriptan were effective (superior to placebo), and well tolerated in treatment of migraine attacks in children and adolescents aged 8-17 and 6-17 years, respectively. No serous adverse effects were observed. The results of this work suggest that nasal sumatriptan 20 mg and rizatriptan 10 mg can be effectively and safely used to treat migraine attacks in adolescents aged over 12 years if more effective drugs than NSAIDs are needed. No difference was observed in efficacy or safety of nasal sumatriptan and rizatriptan between children aged younger than 12 years and older children, but because the treated number of patients under 12 years is still small, more studies are needed before sumatriptan or rizatriptan can be recommended for use in this population. Sleeping during migraine attacks was very common, and most children at least occasionally slept during an attack. Falling asleep was especially common in children under eight years of age and during the first hour after the onset of attack. Children who were able to sleep soon after attack onset were more likely pain-free at two hours. Sleeping probably both improves recovery from a migraine attack and is a sign of headache relief. Falling asleep should be classified as a sign of headache relief in clinical drug trials when studying migraine treatments in children and adolescents.

Immune mechanisms in atherosclerosis; Focus on the role of the complement system

Atherosclerosis is an inflammatory disease characterized by accumulation of lipids in the inner layer of the arterial wall. During atherogenesis, various structures that are recognized as non-self by the immune system, such as modified lipoproteins, are deposited in the arterial wall. Accordingly, atherosclerotic lesions and blood of humans and animals with atherosclerotic lesions show signs of activation of both innate and adaptive immune responses. Although immune attack is initially a self-protective reaction, which is meant to destroy or remove harmful agents, a chronic inflammatory state in the arterial wall accelerates atherosclerosis. Indeed, various modulations of the immune system of atherosclerosis-prone animals have provided us with convincing evidence that immunological mechanisms play an important role in the pathogenesis of atherosclerosis. This thesis focuses on the role of complement system, a player of the innate immunity, in atherosclerosis. Complement activation via any of the three different pathways (classical, alternative, lectin) proceeds as a self-amplifying cascade, which leads to the generation of opsonins, anaphylatoxins C3a and C5a, and terminal membrane-attack complex (MAC, C5b-9), all of which regulate the inflammatory response and act in concert to destroy their target structures. To prevent uncontrolled complement activation or its attack against normal host cells, complement needs to be under strict control by regulatory proteins. The complement system has been shown to be activated in atherosclerotic lesions, modified lipoproteins and immune complexes containing oxLDL, for instance, being its activators. First, we investigated the presence and role of complement regulators in human atherosclerotic lesions. We found that inhibitors of the classical and alternative pathways, C4b-binding protein and factor H, respectively, were present in atherosclerotic lesions, where they localized in the superficial proteoglycan-rich layer. In addition, both inhibitors were found to bind to arterial proteoglycans in vitro. Immunohistochemical stainings revealed that, in the superficial layer of the intima, complement activation had been limited to the C3 level, whereas in the deeper intimal layers, complement activation had proceeded to the terminal C5b-9 level. We were also able to show that arterial proteoglycans inhibit complement activation in vitro. These findings suggested to us that the proteoglycan-rich layer of the arterial intima contains matrix-bound complement inhibitors and forms a protective zone, in which complement activation is restricted to the C3 level. Thus, complement activation is regulated in atherosclerotic lesions, and the extracellular matrix is involved in this process. Next, we studied whether the receptors for the two complement derived effectors, anaphylatoxins C3a and C5a, are expressed in human coronary atherosclerotic lesions. Our results of immunohistochemistry and RT-PCR analysis showed that, in contrast to normal intima, C3aR and C5aR were highly expressed in atherosclerotic lesions. In atherosclerotic plaques, the principal cells expressing both C3aR and C5aR were macrophages. Moreover, T cells expressed C5aR, and a small fraction of them also expressed C3aR, mast cells expressed C5aR, whereas endothelial cells and subendothelial smooth muscle cells expressed both C3aR and C5aR. These results suggested that intimal cells can respond to and become activated by complement-derived anaphylatoxins. Finally, we wanted to learn, whether oxLDL-IgG immune complexes, activators of the classical complement pathway, could have direct cellular effects in atherogenesis. Thus, we tested whether oxLDL-IgG immune complexes affect the survival of human monocytes, the precursors of macrophages, which are the most abundant inflammatory cell type in atherosclerotic lesions. We found that OxLDL-IgG immune complexes, in addition to transforming monocytes into foam cells, promoted their survival by decreasing their spontaneous apoptosis. This effect was mediated by cross-linking Fc receptors with ensuing activation of Akt-dependent survival signaling. Our finding revealed a novel mechanism by which oxLDL-IgG immune complexes can directly affect the accumulation of monocyte-macrophages in human atherosclerotic lesions and thus play a role in atherogenesis.

Neurological manifestations and molecular genetics of acute intermittent porphyria in North Western Russia

Acute intermittent porphyria (AIP, MIM #176000) is an inherited metabolic disease due to a partial deficiency of the third enzyme, hydroxymethylbilane synthase (HMBS, EC: 4.3.1.8), in the haem biosynthesis. Neurological symptoms during an acute attack, which is the major manifestation of AIP, are variable and relatively rare, but may endanger a patient's life. In the present study, 12 Russian and two Finnish AIP patients with severe neurological manifestations during an acute attack were studied prospectively from 1995 to 2006. Autonomic neuropathy manifested as abdominal pain (88%), tachycardia (94%), hypertension (75%) and constipation (88%). The most common neurological sign was acute motor peripheral neuropathy (PNP, 81%) often associated with neuropathic sensory loss (54%) and CNS involvement (85%). Despite heterogeneity of the neurological manifestations in our patients with acute porphyria, the major pattern of PNP associated with abdominal pain, dysautonomia, CNS involvement and mild hepatopathy could be demonstrated. If more strict inclusion criteria for biochemical abnormalities (>10-fold increase in excretion of urinary PBG) are applied, neurological manifestations in an acute attack are probably more homogeneous than described previously, which suggests that some of the neurological patients described previously may not have acute porphyria but rather secondary porphyrinuria. Screening for acute porphyria using urinary PBG is useful in a selected group of neurological patients with acute PNP or encephalopathy and seizures associated with pain and dysautonomia. Clinical manifestations and the outcome of acute attacks were used as a basis for developing a 30-score scale of the severity of an acute attack. This scale can easily be used in clinical practice and to standardise the outcome of an attack. Degree of muscle weakness scored by MRC, prolonged mechanical ventilation, bulbar paralysis, impairment of consciousness and hyponatraemia were important signs of a poor prognosis. Arrhythmia was less important and autonomic dysfunction, severity of pain and mental symptoms did not affect the outcome. The delay in the diagnosis and repeated administrations of precipitating factors were the main cause of proceeding of an acute attack into pareses and severe CNS involvement and a fatal outcome in two patients. Nerve conduction studies and needle EMG were performed in eleven AIP patients during an acute attack and/or in remission. Nine patients had severe PNP and two patients had an acute encephalopathy but no clinically evident PNP. In addition to axonopathy, features suggestive of demyelination could be demonstrated in patients with severe PNP during an acute attack. PNP with a moderate muscle weakness was mainly pure axonal. Sensory involvement was common in acute PNP and could be subclinical. Decreased conduction velocities with normal amplitudes of evoked potentials during acute attacks with no clinically evident PNP indicated subclinical polyneuropathy. Reversible symmetrical lesions comparable with posterior reversible encephalopathy syndrome (PRES) were revealed in two patients' brain CT or MRI during an acute attack. In other five patients brain MRI during or soon after the symptoms was normal. The frequency of reversible brain oedema in AIP is probably under-estimated since it may be short-lasting and often indistinguishable on CT or MRI. In the present study, nine different mutations were identified in the HMBS gene in 11 unrelated Russian AIP patients from North Western Russia and their 32 relatives. AIP was diagnosed in nine symptom-free relatives. The majority of the mutations were family-specific and confirmed allelic heterogeneity also among Russian AIP patients. Three mutations, c.825+5G>C, c.825+3_825+6del and c.770T>C, were novel. Six mutations, c.77G>A (p.R26H), c.517C>T (p.R173W), c.583C>T (p.R195C), c.673C>T (p.R225X), c.739T>C (p.C247R) and c.748G>C (p.E250A), have previously been identified in AIP patients from Western and other Eastern European populations. The effects of novel mutations were studied by amplification and sequencing of the reverse-transcribed total RNA obtained from the patients' lymphoblastoid or fibroblast cell lines. The mutations c.825+5G>C and c.770T>C resulted in varyable amounts of abnormal transcripts, r.822_825del (p.C275fsX2) and [r.770u>c, r.652_771del, r.613_771del (p.L257P, p.G218_L257del, p.I205_L257del)]. All mutations demonstrated low residual activities (0.1-1.3 %) when expressed in COS-1 cells confirming the causality of the mutations and the enzymatic defect of the disease. The clinical outcome, prognosis and correlation between the HMBS genotype and phenotype were studied in 143 Finnish and Russian AIP patients with ten mutations (c.33G>T, c.97delA, InsAlu333, p.R149X, p.R167W, p.R173W, p.R173Q, p.R225G, p.R225X, c.1073delA) and more than six patients in each group. The patients were selected from the pool of 287 Finnish AIP patients presented in a Finnish Porphyria Register (1966-2003) and 23 Russian AIP patients (diagnosed 1995-2003). Patients with the p.R167W and p.R225G mutations showed lower penetrance (19% and 11%) and the recurrence rate (33% and 0%) in comparison to the patients with other mutations (range 36 to 67% and 0 to 66%, respectively), as well as milder biochemical abnormalities [urinary porphobilinogen 47±10 vs. 163±21 mol/L, p<0.001; uroporphyrin 130±40 vs. 942±183 nmol/L, p<0.001] suggesting a milder form of AIP in these patients. Erythrocyte HMBS activity did not correlate with the porphobilinogen excretion in remission or the clinical of the disease. In all AIP severity patients, normal PBG excretion predicted freedom from acute attacks. Urinary PBG excretion together with gender, age at the time of diagnosis and mutation type could predict the likelihood of acute attacks in AIP patients.

Verkkomedian käyttö ja tutkiminen : Iltalehti Online 1995-2001

Marja Heinonen s dissertation Verkkomedian käyttö ja tutkiminen. Iltalehti Online 1995-2001 describes the usage of new internet based news service Iltalehti Online during its first years of existence, 1995-2001. The study focuses on the content of the service and users attitudes towards the new media and its contents. Heinonen has also analyzed and described the research methods that can be used in the research of any new media phenomenon when there is no historical perspective to do the research. Heinonen has created a process model for the research of net medium, which is based on a multidimensional approach. She has chosen an iterative research method inspired by Sudweeks and Simoff s CEDA-methodology in which qualitative and quantitative methods take turns both creating results and new research questions. The dissertation discusses and describes the possibilities of combining several research methods in the study of online news media. On general level it discusses the methodological possibilities of researching a completely new media form when there is no historical perspective. The result of these discussions is in favour for the multidimensional methods. The empiric research was built around three cases of Iltalehti Online among its users: log analysis 1996-1999, interviews 1999 and clustering 2000-2001. Even though the results of different cases were somewhat conflicting here are the central results from the analysis of Iltalehti Online 1995-2001: - Reading was strongly determined by the gender. - The structure of Iltalehti Online guided the reading strongly. - People did not make a clear distinction in content between news and entertainment. - Users created new habits in their everyday life during the first years of using Iltalehti Online. These habits were categorized as follows: - break between everyday routines - established habit - new practice within the rhythm of the day - In the clustering of the users sports, culture and celebrities were the most distinguishing contents. Users did not move across these borders as much as within them. The dissertation gives contribution to the development of multidimensional research methods in the field of emerging phenomena in media field. It is also a unique description of a phase of development in media history through an unique research material. There is no such information (logs + demographics) available of any other Finnish online news media. Either from the first years or today.

Puolustuskykyinen valtio vai Ruotsin hälytyskello? : Suomen sotilasstrateginen asema kylmän sodan alkuvuosien asiantuntija-arvioissa

The doctoral thesis deals with Finnish and foreign expert s analyses of Finland s military strategic position and defence capability, dating back to the early years of the Cold War. Finland s military high command prepared assessments of the country s strategic position and of the capability of the Defence Forces as grounds for defence planning. Since Finland was located on the Cold War dividing line, the foreign powers were also monitoring the development of Finland s situation. The research carried out had access to the armed forces internal assessments, as well as to analyses prepared by the military intelligence services of Sweden, Britain and the United States. One of the working hypotheses was that after the WWII the ability military leadership to estimate the security political needs of the country and the organisation of its defence was severely weakened so that the dangers of the international development were not perceived and the gradual erosion of defence capability was partly unnoticed. This hypothesis proved to be wrong. Even if the Finnish military intelligence was much weaker than during the war, it was able to provide the military leadership with information of the international military development for the most part. The military leadership was also fully aware of the weakening of the defence capability of the country. They faced the difficult task of making the country s political leadership, i.e. President Paasikivi and the government, also understand the gravity of the situation. Only in the last years of his term in office Paasikivi started to believe the warnings of the military. According to another hypothesis, outside observers considered the Finnish armed forces to primarily act as reinforcements for the Soviet Red Army, and they believed that, in the event of a full-scale war, the Finns would not have been able or even willing to resist a Soviet invasion of Sweden and Norway through Finland. The study confirmed that this was approximately the view the Swedes, the British and the Americans had of the Finnish forces. Western and Swedish intelligence assessments did not show confidence in Finland s defence ability and the country was regarded almost as a Soviet satellite. Finland s strategic position was, however, considered slightly different from that of the Soviet-occupied Eastern European countries. Finland had been forced to become part of the Soviet sphere of interest and security system and this was sealed by the Finno-Soviet Treaty of Friendship, Cooperation, and Mutual Assistance in 1948. Finland had little importance to the military interests of the Western powers. In Sweden s defence planning, however, Finland played a significant role as an alarm bell of a possible Soviet surprise attack, as well as defensive frontline and buffer zone.

Ironi som forskningsobjekt. Är det möjligt att forska i det som finns mellan raderna?

Abstract (Irony as object of research: Is it possible to explore what is between the lines?): The main concern of this article is the interpretation of irony: how is it brought about and how can it be investigated? The method applied is based on authentic texts and their elicited interpretations − a method referred to in this article response analysis. Interpretation of irony in the approach taken is seen as being crucially dependent on the notion of coherence. A text is perceived as being coherent if it (a) makes sense and if it(b) hangs together. Incoherent texts can result in an ironic interpretation; however, the incoherence must also be perceived as being intentional, and intentionality in turn is a sign of the edge of the ironist. Ironic interpretation is defined as a combination of five factors: (1) an ironic edge that (2) reflects the intention of the ironist, and (3) has a target and (4) a victim too. Essential to irony is its fifth factor, the fact that one or more of these four factors must be inferred from co(n)text. This definition of irony is crucial in distinguishing irony from non-irony, and it also helps to discern the differences as well as the similarities between irony and related phenomena.

Lähteiden lumoamat : Henry Biaudet, Liisi Karttunen ja suomalainen historiantutkimus Roomassa 1900-luvun alussa

Enchanted by Sources. Henry Biaudet, Liisi Karttunen and Finnish Historical Research in Rome in the Early Twentieth Century This study traces the scholarly endeavours of Henry Biaudet (1870 1915) and Liisi Karttunen (1880 1957) and "La mission historique finlandaise à Rome" which they founded in 1909. They are forgotten in Finnish historiography, but remain internationally renowned for their contribution to the nunciature studies. By investigating their historical work on the Counter- Reformation era, their roles in the scientific communities of Helsinki and Rome as well as the intersection of politics and science in their scholarly practices the study explores the nature of historical research in general at the turn of the twentieth century. The work covers fields such as historiography, university history and the political use of history. Methodologically the research is based on the analysis and contextualization of published and unpublished sources (e.g. correspondences, university records, scholarly publications and reviews in academic journals). Henry Biaudet criticized the previous research on the Nordic Counter-Reformation for its narrow national scope and sources. He sought out a new approach, including the use of sources in archives all over Europe and the inclusion of the Catholic viewpoint. Accordingly, Biaudet and Karttunen searched for records in archives in Southern Europe. Their unorthodox interpretations were denounced in Finland since the picture they gave of late sixteenth-century Sweden was too different from the national narrative. Moreover, Finnish national identity was firmly rooted in Protestantism, and questioning the benevolence of the Reformation and its main actors was considered as an attack not only against historical truth but also national values. The comparison between Biaudet s and Karttunen s arguments and the accepted narrative in Finland shows how traditional interpretations of the Nordic Reformation were influenced by the Lutheran ethos and European anticlerical rhetoric. Historians have recently paid substantial attention to the political use of history, usually focusing on politicized constructions of the national past. This study shows how research that met the criteria of modern historiography also served political purposes. Conducting research in an international community of historians and publishing ambitious scholarly studies that interested an international audience were ways to create a positive image of Finland abroad. These were not uniquely Finnish ideas but rather ideas shared by the international community of historians in Rome. In this context, scientific pursuits were given a clear political meaning. This enhances our understanding of nineteenth-century historiography being firmly rooted between science and politics.

Complement factor H dysfunction in atypical hemolytic uremic syndrome

Alternative pathway (AP) of complement can be activated on any surface, self or non-self. In atypical hemolytic uremic syndrome (aHUS) the AP regulation on self surfaces is insufficient and leads to complement attack against self-cells resulting usually in end-stage renal disease. Factor H (FH) is one of the key regulators of AP activation on the self surfaces. The domains 19 and 20 (FH19-20) are critical for the ability of FH to discriminate between C3b-opsonized self and non-self surfaces and are a hot-spot for mutations that have been described from aHUS patients. FH19-20 contains binding sites for both the C3d part of C3b and self surface polyanions that are needed for efficient C3b inactivation. To study the dysfunction of FH19-20, crystallographic structures of FH19-20 and FH19-20 in complex with C3d (FH19-20:C3d) were solved and aHUS-associated and structurally interesting point mutations were induced to FH19-20. Functional defects caused by these mutations were studied by analyzing binding of the FH19-20 mutant proteins to C3d, C3b, heparin, and mouse glomerular endothelial cells (mGEnCs). The results revealed two independent binding interfaces between FH19-20 and C3d - the FH19 site and the FH20 site. Superimposition of the FH19-20:C3d complex on the previously published C3b and FH1-4:C3b structures showed that the FH20 site on C3d is partially occluded, but the FH19 site is fully available. Furthermore, binding of FH19-20 via the FH19 site to C3b did not block binding of the functionally important FH1-4 domains and kept the FH20 site free to bind heparin or an additional C3d. Binding assays were used to show that FH20 domain can bind to heparin while FH19-20 is bound to C3b via the FH19 site, and that both the FH19 site and FH20 are necessary for recognition of non-activator surfaces. Simultaneous binding of FH19 site to C3b and FH20 to anionic self structures are the key interactions in self-surface recognition by FH and thereby enhanced avidity of FH explains how AP discriminates between self and non-self. The aHUS-associated mutations on FH19-20 were found to disrupt binding of the FH19 or FH20 site to C3d/C3b, or to disrupt binding of FH20 to heparin or mGEnC. Any of these dysfunctions leads to loss of FH avidity to C3b bearing self surfaces explaining the molecular pathogenesis of the aHUS-cases where mutations are found within FH19-20.