Aim: The current research aimed to study the association between exposure to low-dose radiation fallout after the Chernobyl accident in 1986 and the incidence of cancer in Sweden. Methods: A nationwide study population, selecting information from nine counties out of 21 in Sweden for the period from 1980 – 2010. In the first study, an ecological design was defined for two closed cohorts from 1980 and 1986. A possible exposure response pattern between the exposure to 137Cs on the ground and the cancer incidence after the Chernobyl nuclear power plant accident was investigated in the nine northernmost counties of Sweden (n=2.2 million). The activity of 137Cs at the county, municipality and parish level in 1986 was retrieved from the Swedish Radiation Safety Authority (SSI) and used as a proxy for received dose of ionizing radiation. Information about diagnoses of cancer (ICD-7 code 140-209) from 1958 – 2009 were received from the Swedish Cancer Registry, National Board of Health and Welfare (368,244 cases were reported for the period 1958 to 2009). The incidence rate ratios were calculated by using Poisson Regression for pre-Chernobyl (1980 – 1986) and post-Chernobyl (1986 – 2009) using average deposition of 137Cs at three geographical levels: county (n=9), municipality (n=95), and parish level (n=612). Also, a time trend analysis with age standardized cancer incidence in the study population and in the general Swedish population was drawn from 1980 – 2009. In the second study, a closed cohort was defined as all individuals living in the three most contaminated counties in mid-Sweden in 1986. Fallout of 137Cs was retrieved as a digital map from the Geological Survey of Sweden, demographic data from Statistics Sweden, and cancer diagnosis from the Swedish Cancer Registry, National Board of Health and Welfare. Individuals were assigned an annual 137Cs exposure based on their place of residence (1986 through 1990), from which 5-year cumulative 137Cs exposures were calculated, accounting for the physical decay of 137Cs and changing residencies. Hazard ratios for having cancer during the follow-up period, adjusted for age, sex, rural/non-rural residence, and pre-Chernobyl total cancer incidence, were calculated. Results: No obvious exposure-response pattern in the age-standardized total cancer incidence rate ratios could be seen in the first study. However, a spurious association between the fallout and cancer incidence was present, where areas with the lowest incidence of cancer before the accident coincidentally had the lowest fallout of cesium-137. Increasing the geographical resolution of exposure from the average values of nine counties to the average values of 612 parishes resulted in two to three times higher degree of variance explanation by regression model. There was a secular trend, with an increase in age standardized incidence of cancer from 1980 – 2009. This trend was stronger in the general Swedish population compared to the nine counties of the present study. In the second study, 734,537 people identified were divided into three exposure categories: the first quartile was low exposure (0.0 to 45.4 kBq/m2), the second and third quartiles were intermediate exposure (45.41 to 118.8 kBq/m2), and the fourth quartile was highest exposure (118.81 to 564.71 kBq/m2). Between 1991 and 2010, 82,495 cancer cases were registered in the three counties. Adjusted HRs (95% CI) were 1.03 (1.01 to 1.05) for intermediate exposure, and 1.05 (1.03 to 1.07) for the highest exposure, when comparing to the reference exposure. Conclusion: Using the ecological data, there was no exposure response trend; however, after refining the data to the individual level of exposure, there was an overall exposure response pattern. Nonetheless, due to the time dependency, these results were restricted to the age group of 25 – 49 among males. Using register-based data only, for determining the association between low-dose exposure to radiation and the risk of developing cancer, is difficult since we cannot control for other significant factors that are associated with cancer.

Livsformerna på jorden delas systematiskt in i de tre domänerna bakterier, arkéer och eukaryoter. Arkéer är de mikroorganismer som lever i extrema miljöer såsom hetvattenkällor, sjöar med hög salthalt och i miljöer med extrema pH-värden. De kan existera i miljöer där inga andra organismer överlever men förekommer även rikligt överallt runtomkring oss, exempelvis i människans mage och som normalflora i munnen. Vissa bakterier och arkéer har genen för enzymet ammoniak monooxygenas (AMO). Detta enzym spelar en viktig roll vid rening av avloppsvatten genom att oxidera ammonium till nitrit. Syftet med detta examensarbete har varit att detektera arkéer i prover av aktivt slam vilket gjordes genom att optimera en Polymerase Chain Reaction (PCR) baserad metod. Först pelleterades slamproverna via centrifugering för att kunna preparera DNA. Detta DNA användes som templat för optimering av PCR med specifika primers för AMO genen hos arkéer. De PCR produkter som erhölls från det optimerade programmet klonades och transformerades in i Escherichia coli. Därefter sekvenserades PCR produkterna för att identifiera vilka ammonium oxiderande arkéer som fanns i proverna. De amplifierade gensekvenserna visade god överensstämmelse med den förväntade nukleotidsekvensen för arkéer. Samtliga gensekvenser passade bäst in på icke odlingsbara arkéer enligt databasen BLAST. Genom att välja bort icke odlingsbara arkéer i sökningen kunde arkéen Nitrosopumilus maritimus identifieras, vilket är en av få odlade arkéer med AMO-genen sekvens bestämd.

No description available.

RenewFuncBarr

No description available.

The aims of this study are to synthesize and produce a single-chain antibody (scFv) of the anti-cytokeratin 8 monoclonal IgG antibody TS1 and to functionally map amino acid residues important for the interaction with its antigen and the anti-idiotypic antibody TS1. The TS1 antibody has been shown to be effective in binding cytokeratin 8 (CK8) expressed in tumors in vivo and is proposed to be useful in immunotargeting and/or immunotherapy. The anti-idiotypic antibody TS1 can be used to regulate the tumor:non-tumor ratio. Mutagenesis of certain amino acid residues can be used to alter the affinity to improve the tumor:non-tumor ratio further. In the present study, the TS1 IgG was chemically modified to specify groups of residues important for interaction with both CK8 and TS1. If important residues were found in the CDRs, they were mutated in the TS1 scFv construct and the effect was studied using ELISA. The main conclusions drawn from this study are that the important amino acid residues in TS1 for the interaction with both CK8 and TS1 are mainly tyrosines, charged residues and a tryptophan. A central interacting interface was identified with the somewhat unusual participation of residues in the CDR 2 of the light chain. Mutations which resulted in increased affinity to both CK8 and TS1 were also identified.

QC 20110117

<p>Examen i vårdadministration, YH-utbildning: 20 Yh-poäng</p>

In this thesis, quantum chemical methods have been used to shed light on the reaction mechanisms of several dinuclear zinc enzymes. The enzymes studied are involved in the hydrolysis of phosphates, amides, and carboxylic esters, namely RNase Z, Dihydroorotase (DHO), and N-acyl homoserine lactone hydrolase (AHL lactonase). The density functional method B3LYP, together with quite large active site models, was used to investigate these enzymatic reactions. Several plausible proposed mechanisms, involving protonation states of important active site residues (DHO), substrate orientations (AHL lactonase), have been considered. The calculated energetics can be used to assess the feasibility of the suggested reaction mechanisms. Based on the calculations and also on other related dinuclear zinc enzymes studied previously, some general mechanistic features have been uncovered. For all three enzymes, the nucleophilicity of the bridging hydroxide is shown to be sufficient to perform the nucleophilic attack on the substrates. During the attack, the negative charge is transferred from the bridging hydroxide to the substrate oxygen (P=O or C=O). For phosphate hydrolysis, an in line attack have been suggested for RNase Z. In addition, the two zinc ions in RNase Z are directly involved in stabilizing the negative charge in the penta-coordinated transition states. For carbonyl substrates, only one zinc ion participates in the oxygen anion stabilization in the transition states and the tetrahedral intermediates. Furthermore, the enzymes always use the zinc ion with less negatively-charged ligands to play such role. All the substrates investigated have poor leaving groups. Therefore, either the zinc ions or some active site residues help the cleavage of the scissile bond. For RNase Z, a Glu-His diad was suggested to protonate the leaving group. For DHO, an Asp residue was shown to transfer a proton from the bridging hydroxide to the leaving group nitrogen. For AHL lactonase, a zinc ion was also observed to stabilize the leaving oxygen anion.

Bronopol (2-brom-2nitropropan-1,3-diol) occurs in many products, for example cosmetics, medicines and industrial water systems. In this thesis Bronopol was investigated to see if it is an environmental problem in Sweden. As a starting point two existing analysis methods was used to combine to one. The first one was suited for phenol analysis and the other one for Bronopol analysis. The combined method was optimized as far as possible, although this wasn’t achieved as hoped. The cause of this was due to errors beyond our explanation. Because of this problem the yield couldn’t be determined. The water samples were taken from Tekniska Verken in Linköping, Sweden. It was two samples, one incoming and one outgoing sample from the waste water treatment plant. The samples were filtered and then they were passed through SPE columns. The samples were evaporated to dryness with N2. After this the samples were derivatizised with TMS and the following step was GC analysis with EC – detector. Bronopol was detected in the incoming water sample. / Bronopol (2-brom-2nitropropan-1,3-diol) förekommer i dagens läge i en mängd olika produk-ter, allt från kosmetika till läkemedel samt inom industrier. I denna studie utreddes det om Bronopol i dagens läge är ett miljöproblem. Som utgångspunkt i studien användes två olika metoder, den ena analysmetoden var anpassad för fenoler och den andra var anpassad för Bronopolanalys. Dessa två analysmetoder kombi-nerades till en metod för att analysera Bronopol. Därefter optimerades den på bästa möjliga sätt. Dock gick inte optimeringen så bra. På grund av fel som inte kunde förklaras kunde inget utbyte bestämmas i samband med analys av vattenproverna. Vattenproverna togs från Tekniska Verken i Linköping och det var ett ingående samt ett utgå-ende vattenprov från avloppsreningsverket. Proverna filtrerades med Büchnertratt och Munk-tellfilter. Därefter fick proverna gå igenom SPE – kolonnen och sedan indunstades proverna till torrhet med N2. Innan proverna applicerades på SPE – kolonnerna konditionerades de med etylacetat, metanol samt surgjort vatten. Efter det analyserades proverna med gaskromatografi med en EC – detektor. Bronopol detekterades i det ingående vattenprovet men inte i det utgående.