Campylobacter are probably the most important bacterial pathogen related to food-borne illnesses; specifically, gastroenteritis and diarrheal diseases. These bacteria can be isolated from various environments, but always originate from the intestine of warm blooded animals. Particularly, Campylobacter are found in the intestinal tract of poultry, and due to contamination of poultry meat and also further contamination of other food they can cause human infections. Sometimes this results in larger outbreaks, such as during 2016-2017 in Sweden where thousands of persons got infected by a single strain of Campylobacter jejuni sequence type 918 (ST-918). The same strain was also identified amongst a large number of poultry farms and suspicions were directed towards dirty transport cages for poultry as a main route for transmitting the strain between different farms. Similar scenarios with large outbreaks related to one or two single strains (ST-50 and ST-257) had also been observed in previous years and this raised questions about certain strains being especially adapted to survive outside the intestine. The aim here was to examine whether outbreak strains and other strains of C. jejuni have different potential to resist different stress conditions that may be encountered between the poultry farm and the human intestine.

The epidermis is composed of multiple cell strata where viable keratinocytes, in the basal layer (stratum basale (SB)), go through a range of steps with the final stage of being dead corneocytes in the outer most layer (stratum corneum (SC)). The differentiation, which can be thought of as programmed cell death, include several key processes that are essential for an intact skin barrier. The route from SB to SC is accompanied by changes, such as osmotic pressure and pH, that are believed to trigger some of these processes. In this project, HaCaT cells were incubated with, commonly used, skin care substances (urea, glycerol, transcutol and salicylic acid) to assess their impact on cell viability, by MTT-assay, and gene expression, by qPCR. Further, the relationship between osmotic pressure, viability and gene expression was studied. The excipients showed a dose-dependent decrease of keratinocyte viability which also was explained by elevated osmotic pressure when concentration was increased. Exceptions were however observed for transcutol, which showed protective features against osmotic stress. Upregulation of the genes were mainly observed when cells were treated with high concentrations. Involucrin was affected by the substances to a greater extent when compared to other markers. The upregulation of involucrin was however seen to be driven by the osmotic pressure rather than biological effects of the molecules. The project conclude that the viability and gene expression of the keratinocytes are highly related to the osmotic pressure and probably influences the differentiation to a greater extent than the molecules themselves.

Natural products and their derivatives have and are still used by humans for various health ailments due to their rich sources of drug discovery. New biologically active compounds from natural products play a key role in drug development. Marine sponges and their associated microbes contain a lot of bioactive compounds that are potential for drug development. These compounds produce chemical compounds with useful pharmaceutical properties such as antitumor, anti-infective, anti-inflammatory, and antibacterial properties. The main focus of this project was on the antibacterial activity of six different sponge specimens. The aim was to screen the antibacterial activity of the sponge specimen’s extracts. In order to do so, a Minimum Inhibitory Concentration assay was performed to screen the sponge's antibacterial activity against E. coli and S. aureus. Analytical HPLC was used for separation and Solid Phase Extraction (SPE) was used for determining the effect of salts towards the inhibition of anti-bacterial activity for two selected extracts. Ethanolic extract of Stylissa massa showed antibacterial activity against S. aureus. SPE would be a rapid purification step to remove the salts present in sponges at a high concentration but it has not shown a significant effect on the inhibition of antibacterial activity. However, further separation and purification need to be done to be able to completely screen for all the six different sponge specimens.

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The present thesis concerns theoretical studies of molecular interactions investigated by infrared and X-ray spectroscopic techniques, with emphasis on using the two technologies combined in pump probe experiments. Three main types of studies are addressed: the use of near-edge X-ray absorption fine structure spectra (NEXAFS) to manifest through-bond and through-space interactions; the role of hydrogen bonding on the formation of X-ray photoelectron spectra as evidenced by simulations of the water dimer; and the development of theory, with sample applications, for infrared X-ray pump probe spectroscopy - the main theme of the thesis. Ab initio calculations indicate that NEXAFS spectra give direct information about the through-bond and through-space interactions between vacant non-conjugated π* orbitals. It is found that the X-ray photoelectron spectrum of the water dimer differs strongly from the monomer spectrum in that two bands are observed, separated by the chemically shifted ionization potentials of the donor and the acceptor. The hydrogen bond is responsible for the anomalously strong broadening of these two bands. The studies show that X-ray core electron ionization of the water dimer driven by an infrared field is a proper technique to prove the proton transfered state contrary to conventional X-ray photoelectron spectroscopy. Our simulations of infrared X-ray pump-probe spectra were carried out using wave packet propagation techniques. The physical aspects of the proposed new X-ray spectroscopic method - phase sensitive Infrared - X-ray pump probe spectroscopy - are examined in detail in two sample applications - on the NO molecule and on the dynamics of proton transfer in core ionized water dimer. It is found that the phase of the infrared pump field strongly influences the trajectory of the nuclear wave packet on the ground state potential. This results in a phase dependence of the X-ray pump probe spectra. A proper choice of the delay time of the X-ray pulse allows to directly observe the X-ray transition in the proton transfered well of the core excited potential. / QC 20101125

Cardiac hypertrophy is when heart muscles thicken as an adaptive response to several stimuli. Prolonged pathological cardiac hypertrophy can lead to heart failure and severe cardiovascular diseases. Scientists have faced challenges in studying cardiac hypertrophy due to the lack of human cardiomyocytes available. Recently, hypertrophic model using human induced pluripotent stem cell-derived cardiomyocytes was introduced. In this study, expression profiles of in vitroendothelin-1 induced cardiac hypertrophy model were investigated at different time points. The study aimed to examine molecular pathways associated with cardiac hypertrophy, identify biomarker candidates for cardiac hypertrophy, and investigate if there were known pharmaceuticals that putatively are targeting the suggested candidate biomarkers. Using the Ingenuity pathway analysis (IPA) software, GRM1, NPPA, and STC1 gene were identified as biomarker candidates for cardiac hypertrophy model across all time points. More biomarker candidates unique to the cardiac hypertrophy-stages were also identified using IPA. In vivomicroarray data of hypertrophied heart profiles were also used to compare to the in vitro data and preliminarily validate the gene candidates identified by IPA. Four genes were identified by IPA and were presented in the in vivo data. IPA also revealed the in activation of specific pathways of the early-stage cardiac hypertrophy model. The result suggested that the molecular mechanisms of the in vitro cardiac hypertrophy model did not fully represent the actual hypertrophic condition of the heart. More research and validation are required to understand the underlying mechanism fully and potentially, in the future, utilize the identified genes as cardiac hypertrophy biomarkers.

This thesis, written by Ingrid Öberg Månsson at KTH Royal Institute of Technology and entitled “Electroanalytical devices with fluidic control using textile materials and methods”, presents experimental studies on the development of textile based electronic devices and biosensors. One of the reasons why this is of interest is the growing demand for integrated smart products for wearable health monitoring or energy harvesting. To enable such products, new interdisciplinary fields arise combining traditional textile technology and electronics. Textile based devices have garnered much interest in recent years due to their innate ability to incorporate function directly into, for example, clothing or bandages by textile processes such as weaving, knitting or stitching. However, many modifications of yarns required for such applications are not available on an industrial scale. The major objective of this work has been to study how to achieve the performance necessary to create electronic textile devices by either coating yarns with conductive material or using commercially available conductive yarns that are functionalized to create sensing elements. Further, liquid transport within textile materials has been studied to be able to control the contact area between electrolyte and electrodes in electrochemical devices such as sensors and transistors. Yarns with specially designed cross-sections, traditionally used in sportswear to wick sweat away from the body and enhance evaporation, was used to transport electrolyte liquids to come in contact with yarn electrodes. The defined area of the junction where the fluidic yarn meets the conductive yarn was shown to increase stability of the measurements and the reproducibility between devices. The results presented in the two publications of this thesis as well as additional results presented in the thesis itself show the promising potential of using textile materials to integrate electronic and electrochemical functionality in our everyday life. This is shown by using basic textile materials and processing techniques to fabricate complex devices for various application areas such as sensors and diagnostics as well as electrical and energy harvesting components. / Denna avhandling, skriven av Ingrid Öberg Månsson vid Kungliga Tekniska Högskolan och titulerad ”Elektroanalytiska sensorer med vätskekontroll integrerad genom användande av textila material och metoder”, presenterar experimentella studier inom utvecklingen av textilbaserade elektroniska komponenter och biosensorer. Detta är av intresse på grund av den ökade efterfrågan på integrerade smarta produkter som till exempel bärbara sensorer för hälsoövervakning eller för att samla upp och konvertera energi till elektricitet. För att möjliggöra denna typ av produkter föds nya interdisciplinära fält där traditionell textilteknologi och elektronik möts. Textilbaserade enheter har väckt stort intresse under de senaste åren på grund av den naturliga förmågan att integrera funktion i till exempel kläder eller förband genom textila tillverkningsprocesser som väveri, stickning eller sömnad. Många modifikationer hos garner som krävs för att möjliggöra sådana tillämpningar är dock inte tillgängliga i större skala. Därför har det huvudsakliga syftet med denna studie varit att undersöka hur man kan uppnå den prestanda som krävs för att tillverka elektroniska textila komponenter, antingen genom att belägga garner med elektroniskt ledande material eller genom att använda kommersiellt tillgängliga ledande garner som sedan modifieras kemiskt för att skapa sensorer. Utöver detta har vätsketransport inom textila material studerats för att kunna styra och kontrollera kontaktytan mellan elektrolyt och elektroder i elektrokemiska enheter så som sensorer och transistorer. Garner med speciella tvärsnitt, som traditionellt använts i sportkläder för att transportera svett bort från kroppen och underlätta avdunstning, har använts för att transportera elektrolytvätska till elektroder av garn. Den definierade kontaktytan där det vätsketransporterade garnet korsar elektrodgarnet har visats öka stabiliteten av mätningen och reproducerbarheten mellan mätenheter. Resultaten som presenteras i de två artiklar som denna avhandling bygger på samt i avhandlingen själv visar på lovande potential för användandet av textila material för att integrera elektronisk och elektrokemisk funktionalitet i våra vardagsliv. Detta har uppnåtts genom att använda grundläggande textila material och tillverkningsprocesser för att tillverka komplexa enheter för olika tillämpningsområden så som sensorer för diagnostik samt elektroniska komponenter. / <p>QC 2020-08-21</p>

To improve the efficacy of the dendritic cell vaccine Alv B DC from Alv B, the PD-L1 expression in cancer cells was attempted to be reduced through a transfection with a custom designed siRNA. Before transfecting the dendritic cells, the siRNA functionality had to be tested through flow cytometry, that resulted in negative results and therefore led to a RT-qPCR protocol that indicated that the siRNA was functional. Protocols for the two methods were developed and a cell line expressing PD-L1 was set up as a tool for testing. The final goal of testing the effects in Alv B DC was never performed due compromising time but the positive result from the PCR provides a promising start to further testing.

The increase in demand for food has resulted in increased demand for tools that help streamline plant breeding process in order to create new varieties of crops. Identifying the underlying genetic mechanism of favourable characteristics is essential in order to make the best breeding decisions. In this project we have developed a modified autoencoder model which allows for lateral phenotype injection into the latent layer, in order to identify causal SNPs for phenotypes of interest in wheat. SNP and phenotype data for 500 samples of Lantmännen SW Seed provided by Lantmännen was used to train the network. Artificial phenotype created using a single SNP was used during training instead of real phenotype, since the relationship between the phenotype and SNP is already known. The modified training model with lateral phenotype injection showed significant increase in genotype concordance of the artificial phenotype when compared to the control model without phenotype injection. Causal SNP was successfully identified by using concordance terrain graph, where the difference in concordance of individual SNPs  between the modified modified model and control model was plotted against the genomic position of each SNP. The model requires further testing to elucidate its behaviour for phenotypes linked to multiple SNPs.

Poor prognosis for high-risk neuroblastoma patients makes it necessary to find novel treatmentstrategies. This work aims to understand the cell cycle behavior of various high-riskneuroblastoma cell lines following chemotherapy treatment. Here, we mapped the expressionof cell cycle dependent proteins, p21 and p27, in seven high-risk neuroblastoma celllines. All cell lines showed an overall impaired growth following doxorubicin treatment.However, regrowth was observed in all cell lines between day 6 to 15 by forming colonies.The expression of p21 and p27 was measured in all cell lines showing an upregulationof p21 in 3 out of 5 p53 mutated cell lines while it was downregulated in the 2 cell lineswith a p53 wild type. Furthermore, inhibition assays using inhibitors of CHK1/2, p21 ,andSKP2 were performed. The results were promising as the CHK1/2 inhibitor reduced cellviability in all tested cell lines, while the p21 inhibitor had an effect in 3 out of 6 testedcell lines and the SKP2 inhibitor in 4 out of 6 tested cell lines. Confluency measurementover 15 days showed impaired growth following treatment with the CHK1/2 inhibitor for3 out of 6 tested cell lines and p21 inhibitor in 1 out of 6 tested cell lines. The obtainedresults were encouraging and might aid in finding a novel treatment strategy preventingresistance and relapse in neuroblastoma. However, further studies are needed in order tovalidate the efficacy and safety of these promising drugs in neuroblastoma patients. / Dålig prognos för högrisk neuroblastompatienter gör det nödvändigt att hitta nya behandlingsstrategier.Detta arbete syftar till att förstå cellcykelbeteendet hos olika högrisk neuroblastomcellinjerefter kemoterapibehandling. I denna studie kartlades uttrycket av cellcykelberoendeproteinerna, p21 och p27, i sju högrisk neuroblastomcellinjer. Alla cellinjervisade en total nedsatt tillväxt efter doxorubicinbehandling. Återväxt observerades emellertidmellan dag 6 och 15 genom bildandet av kolonier. Uttrycket av p21 och p27 mättesi alla cellinjer. Resultaten visade en uppreglering av p21 i 3 av 5 p53-muterade cellinjermedans det nedreglerades i de två cellinjerna med en p53-vildtyp. Vidare utfördes inhiberingsanalysermed användning av hämmare mot CHK1/2, p21 eller, SKP2. Resultatenär lovande då CHK1/2-hämmaren reducerade cellviabiliteten i alla testade cellinjer, medanp21-hämmaren hade en effekt i 3 av 6 testade cellinjer och SKP2 i 4 av 6 testadecellinjer. Konfluensmätning under 15 dagar visade nedsatt tillväxt efter behandling medCHK1/2-hämmaren för 3 av 6 testade cellinjer och p21-hämmare i 1 av 6 testade cellinjer.De erhållna resultaten är lovande och kan hjälpa till att hitta en ny behandlingsstrategi somförhindrar resistens och återfall i neuroblastom. Ytterligare studier behövs emellertid föratt validera effektiviteten och säkerheten för dessa lovande läkemedel hos neuroblastompatienter.