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Infrastruktursatsningar är en stor del av den regionala utvecklingen i Sverige och forskare i ämnet är eniga om att satsningar på infrastruktur genererar en ökad ekonomisk utveckling. Något de fortfarande är oeniga om, är vilka metoder som är lämpliga att använda för att räkna ut effekten av den ekonomiska vinsten. Finns det några som gynnas mer än andra eller till och med missgynnas av dessa infrastrukturprojekt, hur ser det till exempel ut på landsbygden i de samhällen där större vägar tidigare passerat. Har dessa samhällen gynnats av att ha snabbare och enklare pendling till staden, eller har de istället drabbats negativt när motorvägen, som en del livnärde sig på, fått en ny sträcka. Denna forskningsrapport fördjupar sig i en av de största infrastruktursatsningarna i norra Sverige, nämligen ombyggnationen av europaväg 4 (E4) genom Sundsvall. Projektet som pågick mellan år 2010 och 2015 innebar att sträckan från Njurunda i söder till Skönsberg i norr byggdes om samt att Sveriges fjärde längsta bro anlades över Sundsvallsfjärden. Studien har med hjälp av ortsprismetoden och ortsanalyser utvisat vilken värdeförändring som skett på fastigheter taxerade som småhus, vid detta infrastrukturprojekt. Resultatet av dessa studier visar på den genomsnittliga förändringen av fastighetspriser i områdena Njurundabommen, Nedre Haga/Skönsberg, Nolby/Kvissleby samt Västbo. Data som låg till grund för resultatet visar delvis för få transaktioner, vilket är vanligt vid försäljningsanalyser på ortsnivå. Det genererar i sin tur en osäkerhet i resultatet, vilket medför att förändringarna kan bli stora i förhållande till den verkliga försäljningsutvecklingen. I denna studie minimerades detta genom att två likställda områden slogs ihop samt ett område fick tas bort, vilket slutligen gav ett resultat som indikerar på att områdena i denna studie haft en mer negativ prisutveckling mot Sundsvall och Sverige, sedan området fått en ny infrastruktur i form av E4:an Sundsvall. / Infrastructure investments is a large part of the regional development in Sweden, researchers in the subject agrees that investment in infrastructure generate increased economic development, one thing they still share a disagreement in which calculating methods are suitable. Are there any winners or losers in infrastructure projects, for example, smaller cities in the countryside where highways have previously passed, have they benefited from a quicker and easier commuting to the city, or have they been adversely affected when the highway has been given a new stretch? This research report focuses in one of the largest infrastructure investments in northern Sweden, European road 4 (E4) through Sundsvall. The research, combined with location-based sales comparison method and local analyzes, will show what effect market values will have on the houses real estate’s and what influence the road construction might have regarding to the values of the properties. The results of these studies are shown trough the average changes in property prices in the areas of Njurundabommen, Nedre Haga/Skönsberg, Nolby/Kvissleby and Västbo. However, the result was shown to have too few transactions, which is common in local level sales analyzes. This generates uncertainty in the result, meaning that the values can be large in relation to the actual sales development. The uncertainty was minimized in the results by merging two similar areas, which finally gave a result that indicates that the areas in the study had a more negative development towards Sundsvall and Sweden, since the area received a new infrastructure in the form of the E4 Sundsvall.

Alzheimer's disease (AD) is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Understanding the contributions of different risk factors, toxic proteins, and protein networks to synaptic dysfunction and loss is essential to understanding and one day curing this disease. Oligomeric species of both Aβ and tau are implicated in synapse, however the interaction between them requires further exploration. The first aim of this thesis was to investigate the interaction of Aβ and tau in a novel mouse model AD. In this model APP/PS1 mice were crossed with mice expressing full length wild type human tau (hTau). Expression of hTau in APP/PS1 mice increased plaque size by~50% and increased plaque-associated dystrophic neurites. However, no increase in neurite curvature, neuron loss, or synapse loss was observed in the hTau APP/PS1 animals compared with APP/PS1 alone. The underlying cause of most cases of AD is not known, however genetic risk factors have been identified, the strongest of which is the APOE e4 allele. APOE e4 is associated with increased risk of developing AD and increased rates of cognitive decline compared to the more common APOE e3 allele. The second aim of this thesis was to detect differences in the AD synaptic proteome compared with controls and to also investigate the effect of an APOE e4 allele on those changes. Unbiased label free LC-MS/ MS based proteomics of synapses isolated from human AD and control post-mortem brains of known APOE genotypes was used. Of the 1043 proteins detected in 20 synaptic preparations 17% (173) were found to differ significantly (p < 0.05, fold change >1.2) in AD compared with control. A significant sub-set of these proteins were affected by APOE e4 allele genotype. One of these was Clusterin which was not only increased in the AD synapse but further increased in cases with an APOE e4 allele. Clusterin is closely related to ApoE has also been genetically linked to AD in genome-wide association studies. Aim three was to further investigate the involvement of Clusterin at the synapse and the interaction of ApoE with Clusterin using array tomography. Array tomography confirmed an increase in Clusterin co-localization with presynapses and postsynapses in AD cases compared with controls and found a further increase in cases with an APOE e4 allele. Array tomography also found an increase in synapses which co-localized with Clusterin and Aβ together in cases with an APOE e4 allele. This implies that Clusterin is important in Aβ mediated synapse loss in AD. To further investigate the role of synapse loss in AD aim 4 of this thesis was to develop a novel human based model of Aβ mediated synapse loss. This model uses cortical neurons derived from induced pluripotent stem cells from a control individual that are challenged with Aβ extracted from brains from AD and control individuals. This model shows a significant and concentration dependent reduction in the number of synapses in response Aβ from AD brain but not to control brain extract or AD brain extract immunodepleted of Aβ. The work presented in this thesis has investigated two novel models of AD to assess the effect of known toxic proteins in AD related synapse degeneration. This work also shows that profound protein changes occur at the synapse in AD and that many of these are affected by APOE genotype. Many of these changes potentially cause or contribute to synaptic dysfunction in AD and therefore could be important for therapeutic interventions.

The goal of this master thesis is to study the challenges the contractors are experiencing when building in the project E4 The Stockholm Bypass (E4 Förbifart Stockholm) by using digital models. This is the first step for The Swedish Transport Administration towards the process of implementing BIM in the construction industry, which has led to several challenges and therefore is important to evaluate. The work of building E4 The Stockholm bypass can be seen with a sociotechnical perspective, since both humans and complex technology systems are involved in the project. The study used a qualitative method by interviewing the contractors, the promoters of the model and The Swedish Transport Administration. Furthermore, workshops were held with construction managers, BIM- specialists and the contractors’ measurement surveyors. The results were analysed by the theories regarding Human-Technology-Organisation (HTO), Human-Technology Interaction (HCI) with focus on usability and information management. The study resulted in a couple of recommendation to The Swedish Transport Administration. The main aspects were to involve the contractors earlier in the development of the models; have easily available information in the models necessary for production; change the contractors sceptical attitude towards BIM by listening to their issues; have a clear communication through the existing informations paths and create a common standard of format regarding exchange of information. By following the recommendations, the challenges regarding the work of the contractor will decrease and the implementation of models and BIM could proceed more efficiently.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Cornell University, May, 2009. / Vita. Includes bibliographical references (leaves 128-147).

Submitted by Nuzia Santos (nuzia@cpqrr.fiocruz.br) on 2013-01-24T17:51:01Z No. of bitstreams: 1 Alberto kazuo fuzikawa.pdf: 276958 bytes, checksum: 80d1525e280d315c92a5de15284db642 (MD5) / Made available in DSpace on 2013-01-24T17:51:01Z (GMT). No. of bitstreams: 1 Alberto kazuo fuzikawa.pdf: 276958 bytes, checksum: 80d1525e280d315c92a5de15284db642 (MD5) Previous issue date: 2007 / A apolipoproteína E (apoE) é um gene polimórfico, cujo produto protéico tem múltiplas funções no organismo humano, sobretudo no metabolismo lipídico. Tem sido investigado no contexto do envelhecimento, mas existem poucos estudos em populações bem definidas de idosos em países em desenvolvimento. Os objetivos deste trabalho foram (1) descrever a distribuição dos alelos comuns da apoE ( 2, 3, 4) e seus genótipos, numa população de 1.408 idosos (80,8% de todos os idosos com idade 60 anos) da linha de base da coorte de Bambuí, MG, Brasil, e estudar sua associação com variáveis demográficas (idade, sexo e cor da pele), (2) analisar a associação do polimorfismo da apoE com hipertensão arterial prevalente e variáveis biológicas (pressão arterial sistólica, diastólica, HDL colesterol, LDL colesterol e triglicérides), considerando potenciais fatores de confusão como idade, sexo, fatores de risco cardiovascular, ácido úrico e creatinina séricos. As amostras de DNA foram amplificadas pela reação em cadeia da polimerase e posteriormente digeridas com a enzima de restrição HhaI. O alelo 3 predominou (80,0%), seguido pelo 4 (13,5%) e 2 (6,5%). Todos os seis genótipos possíveis foram observados, sendo o genótipo 3 3 o mais freqüente (63,4%). Esta distribuição é semelhante à descrita em populações ocidentais. A análise de associação com variáveis demográficas foi feita por regressão logística multinomial, usando como variáveis dependentes os três alelos, seis genótipos e o número de alelos 4 por indivíduo. O sexo não se mostrou associado ao número de alelos 4, mas a cor de pele negra apresentou forte associação com a presença de dois alelos 4 (OR ajustado para idade e sexo = 7,38; IC 95% = 1,93-28,25), mostrando que Afro-brasileiros têm alta prevalência do alelo 4, como observado em populações negras Africanas. Nenhuma associação foi encontrada entre idade e o polimorfismo da apoE, sugerindo ausência de associação entre os genótipos e mortalidade nesta população. Hipertensão arterial, definida como pressão arterial sistólica 140 mmHg e / ou diastólica 90 mmHg, ou uso de medicação anti-hipertensiva, apresentou prevalência de 61,3%. Nas análises de associação com a pressão arterial e variáveis biológicas, a variável exploratória foi o genótipo da apoE, classificada em portadores de 2 ( 2 2 e 2 3) e portadores de 4 ( 4 4 e 3 4), tendo como grupo de referência os 3 3. Foram usados modelos de regressão linear múltipla para avaliar a associação com as variáveis biológicas e modelos de regressão de Poisson para estimar as razões de prevalência da hipertensão. Comparados aos homozigotos 3 3, os portadores de 2 tinham níveis séricos mais baixos de LDL colesterol (p < 0,001) e mais altos de triglicérides (p = 0,022), enquanto os portadores de 4 tinham níveis séricos mais altos de LDL colesterol (p = 0,036). Os portadores de 2 e de 4 não mostraram associação com a hipertensão arterial prevalente (razões de prevalência ajustados = 0,94, IC 95% = 0,83-1,07 e 0,98; IC 95% = 0,89-1,07, respectivamente), fornecendo evidência epidemiológica para a ausência de associação entre os genótipos da apoE com a hipertensão arterial prevalente entre idosos. / Apolipoprotein E (apoE) is a polymorphic gene, whose protein product is involved in several key roles in the human body, especially in lipid metabolism. It has been investigated in the context of aging, but there are few studies in well defined populations from developing countries. The objectives of this study were (1) to describe the allelic and genotypic distribution of the common apoE polymorphism ( 2, 3, 4) in a population of 1,408 elderly members (80.8% of all residents 60 years of age) from the baseline of a cohort from Bambuí city, Brazil, and to evaluate its association with demographic variables such as age, gender and skin color and (2) to analyze the association of the apoE polymorphism with prevalent arterial hypertension and biological variables (systolic blood pressure, diastolic blood pressure, HDL cholesterol, LDL cholesterol and triglycerides) in this population, considering potential confounding factors such as age, gender, cardiovascular risk factors, serum uric acid and creatinine. DNA samples were amplified by polymerase chain reaction and then digested with HhaI restriction enzyme. The 3 allele was predominant (80.0%), followed by 4 (13.5%) and 2 (6.5%). All six possible genotypes were observed, with 3 3 being the most frequent (63.4%). This distribution is similar to that described in other western populations. Analysis of association with demographic variables was done by multinomial logistic regression, using as dependent variables the three alleles, six genotypes and the number of 4 alleles per individual. Gender was not associated with the number of 4 alleles, but black skin color was strongly and independently associated with the presence of two 4 alleles (OR adjusted for age and gender = 7.38, 95% CI = 1.93-28.25), showing that African-Brazilians have a high prevalence of the 4 allele, as described in black African populations. No association was found between age and apoE polymorphism, suggesting an absence of association between apoE genotypes and mortality in this population. Arterial hypertension defined as systolic blood pressure 140 mmHg and / or diastolic blood pressure 90 mmHg, or use of antihypertensive medication, was present in 61.3% of participants. For the analysis of association with prevalent arterial hypertension and biological variables the exposure variable was the apoE genotype, divided as 2 carriers ( 2 2 and 2 3) and 4 carriers ( 4 4 and 3 4), having 3 homozygotes as the reference group. Multiple linear regression models were used to study association with biological variables and Poisson regression models to estimate prevalence ratios for hypertension. Compared to the 3 homozygotes, 2 carriers had lower levels of LDL cholesterol (p < 0.001) and higher levels of triglycerides (p = 0.022), while 4 carriers had higher levels of LDL cholesterol (p = 0.036). Neither the 2 or 4 carrier status was associated with hypertension (adjusted prevalence ratios = 0.94, 95% CI = 0.83-1.07 and 0.98, 95% CI = 0.89-1.07, respectively), providing epidemiologic evidence for the lack of association of apoE genotype with prevalent hypertension in old age.

abstract: The apolipoprotein E (APOE) e4 genotype is the most prevalent known genetic risk factor for Alzheimer's disease (AD). In this paper, we examined the longitudinal effect of APOE e4 on hippocampal morphometry in Alzheimer's Disease Neuroimaging Initiative (ADNI). Generally, atrophy of hippocampus has more chance occurs in AD patients who carrying the APOE e4 allele than those who are APOE e4 noncarriers. Also, brain structure and function depend on APOE genotype not just for Alzheimer's disease patients but also in health elderly individuals, so APOE genotyping is considered critical in clinical trials of Alzheimer's disease. We used a large sample of elderly participants, with the help of a new automated surface registration system based on surface conformal parameterization with holomorphic 1-forms and surface fluid registration. In this system, we automatically segmented and constructed hippocampal surfaces from MR images at many different time points, such as 6 months, 1- and 2-year follow up. Between the two different hippocampal surfaces, we did the high-order correspondences, using a novel inverse consistent surface fluid registration method. At each time point, using Hotelling's T^2 test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. / Dissertation/Thesis / Masters Thesis Computer Science 2015

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Introduction: Cognitive impairment is converted for 15% to Alzheimer’s disease (AD), which is incurable. The aim of this study is to investigate whether Herpes simplex virus type 1 (HSV1) and its interaction with allele ε4 of Apolipoprotein E (ApoE-ε4) may be possible risk factors for cognitive impairment. Here, suggestions for implementation of Precision Public Health (PPH) is also presented; population studies of relevant biomarkers of infectious burden and data from health outcomes with the aim of remedying public health crises, monitoring diseases, anticipating risks and using public health initiatives adapted to risk groups to increase understanding of diseases, such as AD. Method: An analysis of 1013 people aged 75 from the cohort, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), was performed. Linear mixed models (LMM) were used to investigate whether anti-HSV1 IgG and ApoE-ε4 are associated with risk of developing cognitive impairment over 5 years. Anti-HSV1 IgG in serum was detected by Enzyme-linked immunosorbent assays and cognitive impairment was examined by Mini Mental State Examination. Results: Neither anti-HSV1 IgG positivity nor its interaction with ApoE-ε4 were associated with cognitive impairment. Discussion: Studies of HSV1 without HSV2 or HSV show mixed results. Therefore, we do not yet have sufficient evidence to implement PPH-interventions against these risks. Other cognitive tests that are more sensitive to early changes and adjustment for underrepresented groups may potentially contribute to a more accurate analysis. / Bakgrund: Kognitiv nedsättning övergår för 15 % till Alzheimers sjukdom (AD) som är obotlig. Denna studie har målsättningen att undersöka om Herpes simplex virus typ 1 (HSV1) och dess interaktion med riskvarianten allel ε4 av genen Apolipoprotein E (ApoE-ε4) kan vara möjliga riskfaktorer för kognitiv nedsättning. I arbetet diskuteras även hur man genom Precision Public Health (PPH) kan studera befolkningen med avseende på relevanta biomarkörer och data från hälsoutfall med syfte att avhjälpa folkhälsokriser, övervaka sjukdomar och förutse risker såsom sjunkande kognition och med folkhälsoinsatser anpassade till riskgrupper öka förståelsen av dessa tillstånd. Metod: En analys av 1013 personer 75 år ur kohorten ”Prospecive Investigation of the Vasculature in Uppsala Seniors” (PIVUS). Linear mixed models (LMM) användes för att undersöka om anti-HSV1 IgG och ApoE-ε4 är associerade med kognitiv nedsättning under 5 år. Anti-HSV1 IgG i serum detekterades med ”Enzyme-linked immunosorbent assays” och kognitiv nedsättning undersöktes med Mini Mental State Examination. Resultat: Anti-HSV1 IgG positivitet var inte associerat med kognitiv nedsättning. Anti-HSV1 IgG positivitet och samtidig ApoE-ε4 var inte heller associerat med kognitiv nedsättning. Diskussion: Andra studier av endast HSV1 utan HSV2 eller HSV visar blandade resultat, varför kunskapsläget idag inte stödjer tillämpning av PPH-interventioner mot dessa risker. Andra kognitiva mått som är känsligare för små förändringar nära intakt kognition samt justering för underrepresenterade grupper kan möjligen bidra till säkrare analys.