999 resultados para Titsingh, Susanna Regina.


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In this work, separation methods have been developed for the analysis of anthropogenic transuranium elements plutonium, americium, curium and neptunium from environmental samples contaminated by global nuclear weapons testing and the Chernobyl accident. The analytical methods utilized in this study are based on extraction chromatography. Highly varying atmospheric plutonium isotope concentrations and activity ratios were found at both Kurchatov (Kazakhstan), near the former Semipalatinsk test site, and Sodankylä (Finland). The origin of plutonium is almost impossible to identify at Kurchatov, since hundreds of nuclear tests were performed at the Semipalatinsk test site. In Sodankylä, plutonium in the surface air originated from nuclear weapons testing, conducted mostly by USSR and USA before the sampling year 1963. The variation in americium, curium and neptunium concentrations was great as well in peat samples collected in southern and central Finland in 1986 immediately after the Chernobyl accident. The main source of transuranium contamination in peats was from global nuclear test fallout, although there are wide regional differences in the fraction of Chernobyl-originated activity (of the total activity) for americium, curium and neptunium.

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Disease maps are effective tools for explaining and predicting patterns of disease outcomes across geographical space, identifying areas of potentially elevated risk, and formulating and validating aetiological hypotheses for a disease. Bayesian models have become a standard approach to disease mapping in recent decades. This article aims to provide a basic understanding of the key concepts involved in Bayesian disease mapping methods for areal data. It is anticipated that this will help in interpretation of published maps, and provide a useful starting point for anyone interested in running disease mapping methods for areal data. The article provides detailed motivation and descriptions on disease mapping methods by explaining the concepts, defining the technical terms, and illustrating the utility of disease mapping for epidemiological research by demonstrating various ways of visualising model outputs using a case study. The target audience includes spatial scientists in health and other fields, policy or decision makers, health geographers, spatial analysts, public health professionals, and epidemiologists.

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Plutarkhoksen ja Uuden testamentin ajan kristillisten kirjoittajien naiskuvaa ja näkemystä avioliitosta ei ole juurikaan vertailtu aiemmin. Molempien teokset on kirjoitettu suunnilleen samoihin aikoihin ja ne esittävät samanlaisen eettisen ideaalin avioliitosta ja puolisoiden rooleista siinä. Plutarkhoksen näkemys avioliitosta näkyy selvimmin hänen teoksessaan Neuvoja vastanaineille. Myös muista Plutarkhoksen teoksista löytyy mainintoja avioliitosta ja puolisoiden rooleista. Uuden testamentin maininnat avioliitosta jakautuvat useisiin eri teksteihin. Evankeliumit käsittelevät avioeroa. Paavali käsittelee avioliittoa yleensä ja seksuaalisuutta avioliitossa. Uuden testamentin myöhemmät kirjeet, varsinkin niiden huoneentaulut, ja apostolisten isien tekstit keskittyvät eniten puolisoiden rooleihin avioliitossa. Plutarkhoksen näkemys avioliitosta oli positiivinen. Tämä näkyy useissa hänen teoksistaan. Kristittyjen kirjoittajien näkemys avioliitosta ei ole niin yksiselitteisen positiivinen. Paavali ei perustele avioliittoa muuten kuin haureuden välttämisellä. Kuitenkin Efesolaiskirjeessä avioliitto käy metaforaksi Kristuksen ja kirkon suhteelle. Plutarkhos ja kristityt kirjoittajat eivät anna paljon ohjeita puolison valinnasta. Plutarkhoksen mukaan puolison valinnassa tulee katsoa hänen luonnettaan, ei varallisuutta tai ulkonäköä. Paavalin ja Ignatioksen mukaan on parempi, jos puoliso on myös kristitty. Kristityt antavat myös ohjeita seka-avioliittoon, jossa puoliso on ei-uskova. 1. Pietarin kirjeen mukaan vaimon tulee pysyä uskossaan, eikä pelätä miestään. Plutarkhoksen mukaan vaimon tulisi palvoa samoja jumalia kuin miehensäkin. Plutarkhos näyttää suhtautuvan naisten aloitteentekoon avioerossa kielteisemmin kuin miesten. Kristityt kirjoittajat suhtautuvat avioeroon kielteisesti, vaikka lieventävätkin Jeesuksen avioerokieltoa. Plutarkhos ei hyväksy miehen aviollista uskottomuutta, mutta antaa miehelle kuitenkin myönnytyksen, jos tämä on liian heikko kontrolloimaan itseään. Kristityt kirjoittajat suhtautuvat uskottomuuteen yksiselitteisen kielteisesti. Ohjeissa avioparille Plutarkhos korostaa avioliiton harmoniaa ja avioparin riitelemättömyyttä enemmän kuin kristityt kirjoittajat. Plutarkhoksen ja kristittyjen kirjoittajien ohjeet vaimolle ovat samanlaisia. Vaimon ihanteelliset ominaisuudet olivat samoja; naisen tuli olla siveellinen ja häveliäs sekä hiljainen. Sekä Plutarkhos että huoneentaulujen kirjoittajat olivat sitä mieltä, että naisen tulisi alistua miehelleen. Plutarkhos ei perustele alistumista mitenkään, kun taas kristityt kirjoittajat antavat aina jonkun perustelun. Yleisin perustelu on apologeettiset syyt. Myös miehelle annettavat ohjeet ovat samanlaiset. Miehen tulee hallita vaimoaan, mutta sekä Plutarkhos että kristityt kirjoittajat rajoittavat miehen hallintavaltaa. Mies toimii myös vaimonsa opettajana. Plutarkhos antaa enemmän ja yksityiskohtaisempia ohjeita seksistä kuin kristityt kirjoittajat. Kristityistä kirjoittajista ainoastaan Paavali paneutuu näihin kysymyksiin tarkemmin. Sekä Plutarkhoksen että Paavalin mukaan ihmisten piti suhtautua seksiin kunnioituksella ja välttää liiallista himoa.

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Despite its rising success, interactive TV (iTV) has found very little attention in the field of HCI. Therefore, the aim of this paper is to investigate the usability of iTV services. It presents the results of a usability test and discusses the implications for further developments. The results show, that prior knowledge of Internet and mobile phones supports the usability of iTV services regarding navigation and text input, while the lack of it leads to great difficulties. Difficult tasks, such as writing a text message, had a success rate of only 20%, while guided tours proofed to be more usable with a success rate of 70%.

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Integrins are heterodimeric transmembrane adhesion receptors composed of alpha- and beta-subunits and they are vital for the function of multicellular organisms. Integrin-mediated adhesion is a complex process involving both affinity regulation and coupling to the actin cytoskeleton. Integrins also function as bidirectional signaling devices, regulating cell adhesion and migration after inside-out signaling, but also signal into the cell to regulate growth, differentiation and apoptosis after ligand binding. The LFA-1 integrin is exclusively expressed in leukocytes and is of fundamental importance for the function of the immune system. The LFA-1 integrins have short intracellular tails, which are devoid of catalytic activity. These cytoplasmic domains are important for integrin regulation and both the alpha and beta chain become phosphorylated. The alpha chain is constitutively phosphorylated, but the beta chain becomes phosphorylated on serine and functionally important threonine residues only after cell activation. The cytoplasmic tails of LFA-1 bind to many cytoskeletal and signaling proteins regulating numerous cell functions. However, the molecular mechanisms behind these interactions have been poorly understood. Phosphorylation of the cytoplasmic tails of the LFA-1 integrin could provide a mechanism to regulate integrin-mediated cytoskeletal interactions and take part in T cell signaling. In this study, the effects of phosphorylation of LFA-1 integrin cytoplasmic tails on different cellular functions were examined. Site-specific phosphorylation of both the alpha- and beta-chains of the LFA-1 was shown to have a role in the regulation of the LFA-1 integrin.Alpha-chain Ser1140 is needed for integrin conformational changes after chemokine- or integrin ligand-induced activation or after activation induced by active Rap1, whereas beta-chain binds to 14-3-3 proteins through the phosphorylated Thr758 and mediates cytoskeletal reorganization. Thr758 phosphorylation also acts as a molecular switch to inhibit filamin binding and allows 14-3-3 protein binding to integrin cytoplasmic domain, and it was also shown to lead to T cell adhesion, Rac-1/Cdc42 activation and expression of the T cell activation marker CD69, indicating a signaling function for Thr758 phosphorylation in T cells. Thus, phosphorylation of the cytoplasmic tails of LFA-1 plays an important role in different functions of the LFA-1 integrin in T cells. It is of vital importance to study the mechanisms and components of integrin regulation since leukocyte adhesion is involved in many functions of the immune system and defects in the regulation of LFA-1 contributes to auto-immune diseases and fundamental defects in the immune system.

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The aim of the study was to evaluate gastrointestinal (GI) complications after kidney transplantation in the Finnish population. The adult patients included underwent kidney transplantation at Helsinki University Central Hospital in 1990-2000. Data on GI complications were collected from the Finnish Kidney Transplantation Registry, patient records and from questionnaires sent to patients. Helicobacter pylori IgG and IgA antibodies were measured from 500 patients before kidney transplantation and after a median 6.8-year follow up. Oesophagogastroduodenoscopy with biopsies was performed on 46 kidney transplantation patients suffering from gastroduodenal symptoms and 43 dyspeptic controls for studies of gastroduodenal cytomegalovirus (CMV) infection. Gallbladder ultrasound was performed on 304 patients after a median of 7.4 years post transplantation. Data from these 304 patients were also collected on serum lipids, body mass index and the use of statin medication. Severe GI complications occurred in 147 (10%) of 1515 kidney transplantations, 6% of them fatal after a median of 0.93 years. 51% of the complications occurred during the first post transplantation year, with highest incidence in gastroduodenal ulcers and complications of the colon. Patients with GI complications were older and had more delayed graft function and patients with polycystic kidney disease had more GI complications than the other patients. H.pylori seropositivity rate was 31% and this had no influence on graft or patient survival. 29% of the H.pylori seropositive patients seroreverted without eradication therapy. 74% of kidney transplantation patients had CMV specific matrix protein pp65 or delayed early protein p52 positive findings in the gastroduodenal mucosa, and 53% of the pp65 or p52 positive patients had gastroduodenal erosions without H.pylori findings. After the transplantation 165 (11%) patients developed gallstones. A biliary complication including 1 fatal cholecystitis developed in 15% of the patients with gallstones. 13 (0.9%) patients had pancreatitis. Colon perforations, 31% of them fatal, occurred in 16 (1%) patients. 13 (0.9%) developed a GI malignancy during the follow up. 2 H.pylori seropositive patients developed gastroduodenal malignancies during the follow up. In conclusion, severe GI complications usually occur early after kidney transplantation. Colon perforations are especially serious in kidney transplantation patients and colon diverticulosis and gallstones should be screened and treated before transplantation. When found, H.pylori infection should also be treated in these patients.

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The systemic autoinflammatory disorders are a group of rare diseases characterized by periodically recurring episodes of acute inflammation and a rise in serum acute phase proteins, but with no signs of autoimmunity. At present eight hereditary syndromes are categorized as autoinflammatory, although the definition has also occasionally been extended to other inflammatory disorders, such as Crohn s disease. One of the autoinflammatory disorders is the autosomally dominantly inherited tumour necrosis factor receptor-associated periodic syndrome (TRAPS), which is caused by mutations in the gene encoding the tumour necrosis factor type 1 receptor (TNFRSF1A). In patients of Nordic descent, cases of TRAPS and of three other hereditary fevers, hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), chronic infantile neurologic, cutaneous and articular syndrome (CINCA) and familial cold autoinflammatory syndrome (FCAS), have been reported, TRAPS being the most common of the four. Clinical characteristics of TRAPS are recurrent attacks of high spiking fever, associated with inflammation of serosal membranes and joints, myalgia, migratory rash and conjunctivitis or periorbital cellulitis. Systemic AA amyloidosis may occur as a sequel of the systemic inflammation. The aim of this study was to investigate the genetic background of hereditary periodically occurring fever syndromes in Finnish patients, to explore the reliability of determining serum concentrations of soluble TNFRSF1A and metalloproteinase-induced TNFRSF1A shedding as helpful tools in differential diagnostics, as well as to study intracellular NF-κB signalling in an attempt to widen the knowledge of the pathomechanisms underlying TRAPS. Genomic sequencing revealed two novel TNFRSF1A mutations, F112I and C73R, in two Finnish families. F112I was the first TNFRSF1A mutation to be reported in the third extracellular cysteine-rich domain of the gene and C73R was the third novel mutation to be reported in a Finnish family, with only one other TNFRSF1A mutation having been reported in the Nordic countries. We also presented a differential diagnostic problem in a TRAPS patient, emphasizing for the clinician the importance of differential diagnostic vigiliance in dealing with rare hereditary disorders. The underlying genetic disease of the patient both served as a misleading factor, which possibly postponed arrival at the correct diagnosis, but may also have predisposed to the pathologic condition, which led to a critical state of the patient. Using a method of flow cytometric analysis modified for the use on fresh whole blood, we studied intracellular signalling pathways in three Finnish TRAPS families with the F112I, C73R and the previously reported C88Y mutations. Evaluation of TNF-induced phosphorylation of NF-κB and p38, revealed low phosphorylation profiles in nine out of ten TRAPS patients in comparison to healthy control subjects. This study shows that TRAPS is a diagnostic possibility in patients of Nordic descent, with symptoms of periodically recurring fever and inflammation of the serosa and joints. In particular in the case of a family history of febrile episodes, the possibility of TRAPS should be considered, if an etiology of autoimmune or infectious nature is excluded. The discovery of three different mutations in a population as small as the Finnish, reinforces the notion that the extracellular domain of TNFRSF1A is prone to be mutated at the entire stretch of its cysteine-rich domains and not only at a limited number of sites, suggesting the absence of a founder effect in TRAPS. This study also demonstrates the challenges of clinical work in differentiating the symptoms of rare genetic disorders from those of other pathologic conditions and presents the possibility of an autoinflammatory disorder as being the underlying cause of severe clinical complications. Furthermore, functional studies of fresh blood leukocytes show that TRAPS is often associated with a low NF-κB and p38 phosphorylation profile, although low phosphorylation levels are not a requirement for the development of TRAPS. The aberrant signalling would suggest that the hyperinflammatory phenotype of TRAPS is the result of compensatory NF-κB-mediated regulatory mechanisms triggered by a deficiency of the innate immune response.