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  • 251.
    Dey, Bonoshree
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Evaluation of peptide-receptor radionuclide therapy in breast cancer and neuroblastoma, in combination with the radio-sensitizing drug VIP-1162018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Cancer being one of the leading causes of death globally, raises an international fight to defeat and finally conquer cancer. It represents more than 200 different diseases that individually have varying symptoms and treatments. The p53-pathway is of great interest as it has shown to be crucial in the formation of cancerous cells. One method is to use peptide-receptor radionuclide therapy to target somatostatin receptors that are overexpressed on cancer cells. The somatostatin-receptor analogue DOTATATE is a peptide that targets these receptors. In this project, the radionuclide (177Lu) is attached to DOTATATE to achieve a localized radiation effect targeting only the tumour cells and not surrounding tissue. In combination with the radiation-sensitizing drug VIP-116, the effect is supposedly enhanced. The findings of this project conclude the specific targeting of 177Lu-DOTATATE and the potential of VIP-116 to act as a radiosensitizer. The combination of both components works more efficiently on some cell lines than others, which emphasizes the need for tailored cancer therapies. 

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  • 252.
    Dey, Bonoshree
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Jenny, Karlsson
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Yacoub, Nicole
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Eklund, Marcus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Jonsson, Matilda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Alternativa Detektionsmetoder för Microarrays2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 253.
    Dharamshi, Jennah
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Abundant and diverse novel bacteria in the deep-sea.2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 254.
    Dhayalan, Sharanya
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    INTERACTION BETWEEN PLASMIN AND AMYLOID BETA PEPTIDE IN ALZHEIMER'S DISEASE2022Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 255.
    Dillström, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Patent som källa för att analysera användning och förekomst av per- och polyfluorerade alkylsubstanser (PFAS)2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 256. Diuk-Wasser, Maria A.
    et al.
    Liu, Yuchen
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Steeves, Tanner K.
    Folsom-O'Keefe, Corrine
    Dardick, Kenneth R.
    Lepore, Timothy
    Bent, Stephen J.
    Usmani-Brown, Sahar
    Telford, Sam R., III
    Fish, Durland
    Krause, Peter J.
    Monitoring Human Babesiosis Emergence through Vector Surveillance, New England, USA2014In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, no 2, p. 225-231Article in journal (Refereed)
    Abstract [en]

    Human babesiosis is an emerging tick-borne disease caused by the intraerythrocytic protozoan Babesia microti. Its geographic distribution is more limited than that of Lyme disease, despite sharing the same tick vector and reservoir hosts. The geographic range of B. microti is expanding, but knowledge of its range is incomplete and relies exclusively on reports of human cases. We evaluated the utility of tick-based surveillance for monitoring disease expansion by comparing the ratios of the 2 infections in humans and ticks in areas with varying babesiosis endemicity. We found a close association between human disease and tick infection ratios in long-established babesiosis-endemic areas but a lower than expected incidence of human babesiosis on the basis of tick infection rates in new disease-endemic areas. This finding suggests that babesiosis at emerging sites is underreported. Vector-based surveillance can provide an early warning system for the emergence of human babesiosis.

  • 257.
    Dolfe, Lisa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Process development for the control of solubility of Affibody® molecules2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this study the aim was to optimize the production of the Affibody fusion-protein Z03358-

    ABD094-(S4G)3-IL2 with regard to the amount of soluble protein produced. However,

    problems with reproducibility with this protein and the chosen expression system were

    encountered. Therefore, expression of the His-tagged Affibody His6-(Z05477)2 was

    evaluated using the same expression system as well as expression in another well

    characterized expression system.

    Both target proteins are of therapeutic interest. One of the proteins is an IL2 fusion

    protein (Z03358-ABD094-(S4G)3-IL2) that bind the platelet-derived growth factor receptor β

    (PDGFR-β). PDGF signaling is of interest in cancer treatment where, among other things, the

    effects of PDGF on tumor angiogenesis is researched. The His6-(Z05477)2 protein has a

    classified target but is developed as a therapeutic in the area of inflammation and autoimmune

    disease. Both model proteins are known to be difficult to purify due to low solubility.

    The two E. coli expression systems investigated and compared were BL21(DE3) and

    Lemo21(DE3). The fusion protein Z03358-ABD094-(S4G)3-IL2 was produced in

    BL21(DE3) in inclusion bodies with a yield of 4.95 g/l. An optimized process for the

    expression of His6-(Z05477)2 using BL21(DE3) was developed with a yield of 6.6 g/l soluble

    protein after expression at 30°C for 6 h.

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    lisadolfe_examensarbete
  • 258.
    Doroszko, Milena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Identification of differentiation programmes and their trajectories in glioblastoma at a single-cell level2023Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 259.
    Doshi, Jiten
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. ETH Zurich.
    A platform for Chinese hamster ovary (CHO) cell genome engineering2016Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    The production of therapeutic recombinant proteins in heterologous systems has gained significance since the last decade. For recombinant proteins that require post-translational modifications (PTMs), mammalian systems are preferred. Chinese hamster ovary (CHO) cells are the mammalian cells of choice for production of recombinant proteins. This is because of their ability to provide correct protein-folding and post-translational modifications, displaying high productivity at large scale, ability to grow in suspension mode at high densities in a serum-free media, incapable of infection by most viruses and their history of regulatory approvals. There is an established state of the art technology for development of CHO cells for recombinant protein production. This technology relies on random integration of the gene of interest and gene amplification process for obtaining high expressing clones. There is a high degree of clonal heterogeneity and instability observed in the screened clones. To overcome the process of random integration, this report describes a lentivirus based screening for search of stable and high expressing integration sites in CHO cells. The integration sites are identified by using nrLAM-PCR (non-restrictive linear amplification mediated PCR) coupled with high throughput sequencing. Lentivirus are chosen as they preferentially integrate within the coding regions rendering the possibility of obtaining stable and high expressing clones. In addition, lentivirus vector is designed to possess landing pad for recombinase mediated cassette exchange of viral sequence with foreign DNA. The report describes a successful cassette exchange reaction but with low efficiency. Genome engineering technologies such as CRISPR/Cas, TALENs can used for targeted gene insertion at integration sites and thus establishing stable and efficient production of recombinant proteins in CHO cells. Additionally, an approach for designing synthetic promoters based on Ef1α promoter architecture has been shown. Synthetic promoters are useful for expression of multi-gene cassettes as they are short in length and provide comparable expression levels to the native mammalian promoter. 

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    Doshi_Jiten_Masters_Thesis
  • 260.
    Doszyn, Olga
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Sex differences in neuronal differentiation of human stem cells2019Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Sexual dimorphism has been long noted in human neurobiology, apparent most notably in sex-biased distribution of multiple neurological disorders or diseases, from autism spectrum disorder to Parkinson's disease. With the advances in molecular biology, genetics and epigenetics have come into focus as key players in sexually dimorphic neural development; and yet, many studies in the field of neuroscience overlook the importance of sex for the human brain.

    For this project, human embryonic and neural stem cells were chosen for three main reasons. Firstly, they provide an easily obtainable, scalable and physiologically native model for the early stages of development. Secondly, neural stem cells populations are retained within the adult human brain, and are implicated to play a role in cognition and mental illness, and as such are of interest in themselves. Thirdly, stem cell lines are widely used in research, including clinical trials of transplantation treatments, and for this reason should be meticulously examined and characterized.

    Here, the morphology, behaviour, and expression of selected genes in four stem cell lines, two of female and two of male origin, was examined in side-by-side comparisons prior to and during neuronal differentiation using a variety of methods including light microscopy, time-lapse two-photon microscopy, quantitative real-time PCR and immunocytochemistry. The obtained results have shown previously uncharacterised differences between those cell lines, such as a higher rate of proliferation but a slower rate of neuronal differentiation in male cell cultures compared to female cells cultivated in the same conditions, and a sex-biased expression of several markers of neuronal maturation at late stages of differentiation, as well as diverse patterns of expression of X- and Y-linked genes involved in stem cell proliferation and neural development.

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  • 261.
    Duarte, Sofia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    The Functions of Ethylene-signaling in the Regulation of Gemma Dormancy and Germination in the Liverwort Marchantia polymorpha2020Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Dormancy was a key strategy for land plant survival and adaptation to changing conditions in the terrestrial habitat. Due to their sessile nature, it allowed plants to release seeds or spores that remain in a dormant state to prevent or delay germination until optimal environmental conditions and genetic factors for growth are perceived. In the liverwort Marchantia polymorpha, gemmae are produced inside gemma cups, specialized receptacles located on the thallus. After being splashed out of the receptacle, usually by rainfall, dispersed gemmae begin to germinate in the presence of light and humidity, producing clonal offspring. Ongoing research indicates that a second signal could promote dormancy of gemmae inside the gemma cup, mediating the interaction between auxin in the thallus and abscisic acid in the gemmae. To attest to this, previously obtained RNAseq gene expression patterns were verified by qRT-PCR, promoter activity of three ethylene receptors was measured and a phenotypic analysis was performed on loss-of-function mutants. Because the RNAseq and phenotypic analysis of the ethylene-constant-signaling mutant Mpctr1 suggested that ethylene could be the best candidate hormone, a gemmae swap experiment was performed. Gemmae were swapped between constant ethylene-signaling mutants and ethylene-insensitive mutants. The findings presented here hint at the fact that ethylene, being a gaseous signal, could be a relevant hormone in the process of dormancy establishment, maintenance and release.

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  • 262.
    Duc, Anne-Valérie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    A comparison of the discrete call repertoires of Northeast Atlantic killer whales (Orcinus orca)2011Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Although Icelandic and Norwegian killer whales are thought to have been in contact prior to the collapse of the herring stock in the 1960s, the Northeast Atlantic killer whales currently seem to show high site fidelity. So far, photoidentification data have suggested movement of a few individuals between East Iceland and North Scotland, and two calls have been shown to be shared by the Icelandic and Norwegian populations. Based on previous and newly analysed call samples, the aim of this study was to describe the geographic variation in the vocal repertoire of the Northeast Atlantic killer whales. Recordings have been conducted off Southwest Iceland in the summers 2004, 2008 and 2009 using sound recording tags attached using suction cups (Dtags), a 4-element vertical hydrophone array and a 2-element towed hydrophone array. From the 57 hours of recording analysed, 1742 calls were classified. In total, 56 distinct call categories composed of 35 call types and 31 subtypes were identified. This discrete call repertoire contained less biphonic calls but more calls composed of buzzes and/or clicks than the Norwegian repertoire. The reasons for these differences remain unknown. One Icelandic call subtype was defined as a compound call, a type of call that is common in the Norwegian population. The comparison of the different vocal repertoires of Northeast Atlantic showed four good or likely call matches in herring-eating killer whales (one between Southwest Iceland and Shetland, one between East Iceland and Norway, and two between Shetland and Norway). No matches were found between Southwest Iceland and East Iceland. I suggest that the four shared calls are most likely to have come from a common ancestral pod and have been transmitted through vocal learning. Over time, geographic isolation of the groups induced by changes in the migratory patterns of the herring might have been accompanied by divergence in their call repertoires.

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    AV-Duc_masterthesis
  • 263.
    Duinkerken, Berend Herman Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Unravelling the role of DENV and the TLR2/6/CD14 axis in viral sensing, attachment and entry2020Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Dengue virus (DENV) annually infects an estimated 390 million humans and half of the global population is at risk of infection. A small fraction of the patients experiences vascular leakage, termed dengue hemorrhagic fever, which can ultimately lead to the potentially lethal dengue shock syndrome. It is thought that the human immune response can protect from DENV but also contribute to pathogenesis. Therefore, it is of great importance to further study and unravel the interactions of DENV with the human immune system. Previous studies have identified Toll-like receptor 2 (TLR2), TLR6 and CD14 to have a role in sensing, attachment and/or entry of dengue virions. Here, intracellular interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) expression levels were measured ex vivo following stimulation with immature dengue virions under TLR2, TLR6 and CD14 blocking conditions. Additionally, the capacity of DENV to infect an African green monkey epithelial kidney cell line (i.e. BS-C-1 cells) was assessed under TLR2 and CD14 blocking conditions. It was found that immature dengue virions induce IL-1β and TNFα expression in monocytes, which could be dampened by blocking TLR2, TLR6 or CD14 prior to exposure. Additionally, infection of BS-C-1 cells could be inhibited by blocking TLR2 but enhanced following blockage of CD14. New methods were explored to further investigate the role of TLR2, TLR6 and CD14 in DENV sensing and infection. A DENV infectious clone was subjected to site-directed mutagenesis to later create mutant DENV particles. A cell-based enzyme-linked immunosorbent assay (ELISA) was optimized and validated to measure bound and internalized DENV in HEK-Blue™ hTLR2 cells. It was also demonstrated that DENV infection of BS-C-1 cells could be visualized by light microscopy in combination with immunofluorescence. Taken together, these findings showed that DENV was sensed by monocytes in a TLR2/6/CD14-dependent manner. Infection of BS-C-1 cells by DENV was shown to be dampened or enhanced by TLR2 and CD14, respectively. Since microscopy could be used to visualize DENV infection, these findings can be used to further investigate these observations. Mutant DENV particles can be used to identify which structural viral protein is involved in these interactions. Additionally, the developed cell-based ELISA can be utilized to further study whether the TLR2/6/CD14 axis is involved in either or both sensing and infection of HEK-Blue™ hTLR2 cells.

    The full text will be freely available from 2025-06-26 15:56
  • 264.
    Dunder, Linda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Effects of developmental low-dose exposure to bisphenol A on the adipose tissue in juvenile Fischer 344 rats: Alterations of adipocyte cell density and mRNA gene expression2015Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    BACKGROUND: Bisphenol A (BPA) is a high volume production chemical, used to manufacture certain polycarbonate plastics and epoxy resins. It is also a well-known endocrine disrupting chemical that can mimic endogenous hormones in the body. BPA has been suggested to play a role in the development of obesity and metabolic disorders. Humans are constantly exposed to low doses of BPA due to its ubiquity and studies have shown that the developmental period early in life seems to be particularly sensitive. This has raised a discussion about the potential risk for human health and in January 2015 the European Food Safety Authority (EFSA) reduced the tolerable daily intake (TDI) from 50 μg/kg bw/day to a preliminary TDI of 4 μg/kg bw/day.

    OBJECTIVES: The aim of this present study was to investigate effects of developmental low-dose exposure to BPA on the early distribution of fat cells and on the expression of several genes of interest for adipogenesis.

    METHODS: Pregnant Fischer 344 rats were exposed to BPA via their drinking water corresponding to 0.5 µg/kg bw/day or 50 µg/kg bw/day, during gestation and lactation, until weaning. The routes of exposure for the offspring were in utero and via lactation. The pups were sacrificed at 5 weeks of age. The mRNA gene expression for several genes involved in adipocyte differentiation was measured using qPCR, and adipose cell density in the gonadal, inguinal and brown adipose tissue was examined histologically.

    RESULTS: Developmental exposure of 0.5 µg BPA/kg bw/day significantly increased (122 %, p < 0.05) early adipogenesis as demonstrated by adipocyte hyperplasia in the inguinal fat depot in female juvenile Fischer 344 rats. This increase (129 %; p < 0.05) was also seen in the inguinal fat depot in male offspring, but in animals exposed to 50 µg BPA/kg bw/day compared to 0.5 µg BPA/kg bw/day, but not compared with control.

    Moreover, the mRNA expression of numerous genes of interest for adipogenesis was significantly altered in both females and males. Most interesting was the observed downregulation (p<0.05) of the gene expression of AdipoR1 in the inguinal and AdipoR2 in the gonadal fat depot in males exposed to the lower dose compared with control.

    CONCLUSIONS: Developmental low dose exposure to BPA, even a dose eight times lower than the current TDI, induced significant effects in juvenile Fischer 344 rats. The increase in the number of fat cells observed in juvenile rats may mirror a major public health problem in relation to the obesity epidemic. Additionally, several genes associated with adipogenesis were altered in both female and male Fischer 344 rats. The effects of BPA occurred within the range of environmentally relevant levels and humans are constantly exposed to low doses of BPA, which concludes that exposure to substances such as BPA should be carefully examined in the etiology of obesity.

  • 265.
    Dunskis, Aivars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Habitat preferences for oviposition and reinforcement experiment of the chequered blue butterfly (Scolitantides orion) in the Stockholm Archipelago2023Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
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    aivars_dunskis_popular_science_summary.pdf
    The full text will be freely available from 2024-09-14 12:00
  • 266.
    Dupuis, Jordan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    CYP2D6 loss of heterozygosity - a potential target for neuroblastoma therapy2023Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Loss of heterozygosity events, whereby alleles are lost at heterozygous chromosomal loci, are associated with cancer formation and may result in the deletion of numerous genes encoding enzymes that have critical activities within the cell. Consequently, vulnerabilities are created that are absent in normal cells which can be targeted using a precision medicine approach called collateral lethality. A recent bioinformatic analysis of genomic variants identified LOH of CYP2D6 as a potential target for neuroblastoma therapy based on the prevalence of LOH occurrence and probability of a loss of function allele at this locus. Neuroblastoma cell lines with unmodified CYP2D6 function and models with enhanced function were screened with a small set of anti-cancer drugs that may be metabolized by CYP2D6. Despite low CYP2D6 expression levels in neuroblastoma cells in comparison to healthy liver tissue, four hits were identified that showed greater potency in tumour cells with low CYP2D6 activity. This study can be used as a framework for evaluating other LOH targets in various cancer types.

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  • 267.
    Dvizac, Nino
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Turismens utsläpp på Gotland2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The tourism industry is accounted for high monetary revenues but is also responsible for a high amount of emissions globally. In this study the emissions from the tourism sector are discussed with a special focus on the Swedish island, Gotland. Because Gotland is an island there are limited ways to travel to the island. There are generally three ways to get to the island, by ferry, airplane or by a cruise ship. Approximately 70% of the tourists travel by ferry and it is therefore the focus of this study. In this study emissions from tourism were calculated by the travel to and from the island, and during the stay. Emissions from transport on the island to various destinations were calculated as well as emissions from accommodations. The result from the study shows that the tourism on Gotland has far lower emissions than the general global tourism. This is mostly due to the low emissions from the electric production in Sweden.

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  • 268.
    Díaz Ubieta, Cristina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Chemistry Data Mining to Discover Molecular Interactions2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In the computational chemistry field, the area of energy functions has not seen any changes for decades, since the functions which were first created still work quite well today. In this project we test to see if we can make improvements to those energy functions by doing data mining on a dataset of off-equilibrium molecule states, with the objective of being able to predict the energy of a molecule just by knowing its structure. We tested what results we could obtain by adding different levels of complexity to represent the structure which describes the molecule and see what contributions each level has to the final energy of the molecule. This was examined for both elements and atom types. As a conclusion, we obtained an energy function which potentially could predict the energies, but further work has to be done to improve this function.

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  • 269.
    Dölfors, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Växters effektorutlösta försvars funktionoch evolution: Ett uthålligt skydd mot patogener?2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The diversity among genes conferring resistance (R) against infectious diseases is very high in the plant kingdom, especially in the effector triggered class of defense. This article describes the interactions between the plant effector triggered immunity and pathogen effectors and examines the evolutionary and genetic mechanisms for the emergence of new resistance. R gene products have a typical domain structure and interacts both directly and indirectly with pathogen effectors. Upon contact with an effector a defense response is triggered that may prevent the further pathogen growth. Multiple genetic mechanisms act simultaneously on the R-genes, which results in a rapid diversification of novel R variants. The intimate co-evolution of many existing plant-pathogen systems form the evolutionary pattern of R genes. Diversifying positive selection via the biological arms race model and conservative negative frequency-dependent selection are both important coevolutionary processes. This article indicates that the plant immune system is adaptive and robust, but also highlights the lack of knowledge in plant resistance research.

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    Växters effektorutlösta försvars funktion och evolution
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    Växter har ett hållbart försvar som utmanar mikroorganismer
  • 270.
    Eckerström Liedholm, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Brain size does not affect reproductive behaviour in male guppies (Poecilia reticulata)2014Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    The processes and mechanisms that govern brain size evolution remain a widely discussed topic in evolutionary biology. How relative brain size relates to animal behaviour and cognition is even more controversial. Recent comparative and experimental studies have shown a positive relationship between relative brain size and complexity of behaviour. Some of the most important behaviours that have direct consequences for an individual’s fitness are reproductive behaviours, and they sometimes require quite complex behavioural repertoires. Selection for complex behaviour might therefore induce an expansion of brain size to allow for cognitively demanding tasks during courtship and mating. In the present study we investigated the effect of relative brain size on reproductive behaviour in male guppies (Poecilia reticulata), using fish from a recently established brain size artificial selection experiment. Females were paired with either a large- or a small-brained male, and we collected data on a suite of male courtship behaviours including sneak copulation attempts, courtship display, gonopodial swings and time spent following the female. Although the extent of orange colouration, a trait that varies across large- and small-brained males, affected male behaviour, we were not able to detect any difference in reproductive behaviour between the brain size selection lines. These results suggest that there is no strong association between male mating behaviour and relative brain size, and future studies will examine this question further. But currently, our results indicate that relative brain size might not be linked to reproductive behaviour to any significant extent, at least not in the guppy.

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  • 271.
    Edblom, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Exploration of big data and machine learning in retail2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    During the last couple of years, there has been an immense increase

    in data generation. This new data era has been referred to as the big

    data paradigm. More and more business areas are today realizing the

    power of capturing more data, and by this hope to reveal hidden

    patterns and gain new insights of their business. ICA is one of the

    largest retail business in Sweden, and saw the potential of utilizing

    the big data technologies to take the next step in digitalisation.

    The objective of this thesis is to investigate the role of these

    techniques in combination with machine learning algorithms and

    highlights advantages and possible limitations. Two use cases were

    implemented and tested which reveals possible application areas and

    important aspects to consider.

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  • 272.
    Edenståhl, Selma
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Enterprise Search for Pharmacometric Documents: A Feature and Performance Evaluation2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Information retrieval within a company can be referred to as enterprise searchWith the use of enterprise search, employees can find the information they need in company internal data. If a business can take advantage of the knowledge within the organization, it can save time and effort, and be a source for innovation and development within the company. 

    In this project, two open source search engines, Recoll and Apache Solr, are selected, set up, and evaluated based on requirements and needs at the pharmacometric consulting company Pharmetheus AB. A requirement analysis is performed to collect system requirements at the company. Through a literature survey, two candidate search engines are selected. Lastly, a Proof of Concept is performed to demonstrate the feasibility of the search engines at the company. The search tools are evaluated on criteria including indexing performance, search functionality and configurability.

    This thesis presents assessment questions to be used when evaluating a search tool. It is shown that the indexing time for both Recoll and Apache Solr appears to scale linearly for less than one hundred thousand pdf documents. The benefit of an index is demonstrated when search times for both search engines greatly outperforms the Linux command-line tools grep and find. It is also explained how the strict folder structure and naming conventions at the company can be used in Recoll to only index specific documents and sub-parts of a file share. Furthermore, I demonstrate how the Recoll web GUI can be modified to include functionality for filtering on document type. 

    The results show that Recoll meets most of the company’s system requirements and for that reason it could serve as an enterprise search engine at the company. However, the search engine lacks support for authentication, something that has to be further investigated and implemented before the system can be put into production. 

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    SelmaEdenståhl_MasterThesis
  • 273.
    Eger, Nicole
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Advanced Detection Methods of Genomic Barcodes for Genotyping Escherichia coli Libraries2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Pooled cell strain libraries are a powerful tool allowing to investigate the influence of genetic modifications on phenotypes in high throughput single-cell assays. To link the genotype to phenotype in each cell of the library, unique 20 base pairs (bp) long barcodes are used to allow in situ genotyping after phenotyping via fluorescence microscopy. In previous studies, these barcode sequences were expressed from high copy number plasmids resulting in a high number of targets for detection via fluorescence in situ hybridization (FISH) and thus, a strong readout signal. However, constant selection pressure must be applied on the cells to maintain the foreign plasmid DNA which may influence the phenotype. Inserting unique barcodes on the chromosome ensures stability of the construct which is required for some genomic library applications. However, the low copy number of the barcode sequence often requires an additional step of DNA amplification for efficient detection. In this study, two methods for barcode amplification were investigated. First, amplification from the double stranded DNA upon binding of peptide nucleic acids and subsequent amplification via rolling circle amplification (AmPPR). Second, amplification from genomic DNA or cDNA via loop-mediated isothermal amplification (LAMP). Whereas the AmPPR approach remained unsuccessful, chromosomal barcode sequences were successfully amplified in situ via LAMP and subsequently detected using FISH. I show that LAMP can potentially be a quick, specific, and elegant amplification technique for in situ genotyping in microfluidic devices. However, nonspecific amplification and partly nonspecific readout signals when using LAMP remain a problem and need to be further investigated before implementing this method on pooled libraries.

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  • 274.
    Ekholm Lodahl, Jennifer
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Analysis of epigenetic changes induced by exposure to a mixture of endocrine disrupting chemicals in the mouse brain and a hippocampus mouse cell model2021Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Prenatal exposure to mixture N1, a chemical mixture consisting of four phthalate diesters,three pesticides and Bisphenol A, has been associated with behavioural changes as well as changes in gene expression in mice. In this study it was investigated whether the changes in gene expression could be explained by changes in DNA methylation. Mixture N1 was found to significantly change DNA methylation in three different genes (Nr3c1, Nr3c2 and Crhr1) on totally eight different Cytosine Guanine dinucleotides (CpG) positions. To further investigate whether these changes could be induced already during differentiation of cells, a hippocampal cell model HT22 was exposed to mixture N1 during differentiation. In this mode, mixture N1 induced a statistically significant change in the promoter region of Nr3c1. Unfortunately, this change could however not be validated, and the experiments would need to be repeated. In conclusion, this study showed that exposure to mixture N1 can result in changes in DNA methylation. 

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  • 275.
    Eklund, Evelina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Are particles in peatland-dominated catchments hotspots for enzymatic activity?2023Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
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  • 276.
    Eklöf, Disa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Survey of mycotoxin producing fungi in goji berries, oil seeds and walnuts on the Swedish market2013Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
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    Survey
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  • 277.
    Ekman, Malin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Undervisning i autentisk miljö: Skillnader i mängd utomhusundervisning, studiebesök och besökande som kommer till skolor och håller i undervisning2016Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Utomhusundervisning, studiebesök och besökande som kommer till skolan och håller i undervisning, är exempel på undervisning i autentiska miljöer. Sådan undervisning har visat sig hjälpa elever med deras inlärning, när det förekommer i kombination med annan undervisning. Syftet med undersökningen var att ta reda på hur mycket undervisning i autentiska miljöer gymnasielärare i ett län i Sverige hade arrangerat i kurserna i naturkunskap läsåret 15/16. För att göra detta skickades en enkät ut till naturkunskapslärarna och deras rektorer i länet, och två av lärarna intervjuades. Nästan alla svarande lärare arrangerade någon typ av undervisning i autentiska miljöer. Utomhus studerades ofta den omgivande miljön. Vid studiebesök gavs eleverna information som rörde platsen de befann sig på. När besökande kom till skolan och höll i undervisningen undervisade de om hälsa, samt sex- och samlevnad.

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    Undervisning i autentisk miljö
  • 278.
    Eksell, Isak
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Determining the developmental history ofpermafrost peatlands across northernFennoscandia using macrofossil analysis2023Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
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  • 279.
    Ekstedt, Elias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Fryckstedt, Inna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Hyllander, Hanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Jonsson, Josefin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Ring, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Wærn, Felix
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    The future of viral vectors for gene therapy2021Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Gene therapy is a fast growing technology that offers treatments for genetic diseases. The method is based on introducing genetic material into a patient to replace the disease-causing gene, using a vector. This report examines the potential of some viral vectors for gene therapy, to give Bio-Works Technologies a recommendation on what the future market demands. Oncolytic viruses, vaccines and gene editing are not treated in the report as a delimitation. 

    Viral vectors have different biological properties and require different purification methods, making them suitable for different applications in gene therapy. In the purification of the viruses it can be challenging to obtain a high purity and large-scale manufacturing. One major drawback with most purification methods is that they are not specific to just one virus, which leads to contaminants in the solution and lower purity. The viral vectors handled in the report are the adenovirus, adeno-associated virus, gammaretrovirus, lentivirus, alpharetrovirus, foamy virus, herpes simplex virus and baculovirus. These were chosen as they are relevant vectors for gene therapy and stay within the scope of the report.

    Lentiviral vectors (LVs) and adeno-associated viral vectors (AAVs) will dominate the gene therapy field in the coming years. This is based on the information that the use of AAVs and LVs in clinical trials have increased in recent years, while the other vectors mentioned above have slightly decreased or show no apparent change. However, challenges still remain in the purification processes. Ligands used in affinity chromatography for purification of AAVs are effective at removing most contaminants, but cannot distinguish between empty and loaded capsids, which can induce immune response when used clinically. This is the main challenge when purifying AAVs. The empty capsids can be removed with ion exchange chromatography, which results in higher purity but also lower recovery. There is no specific purifying method for LVs, therefore a lentivirus-specific affinity ligand, such as an antibody ligand, would be beneficial for the purification and manufacturing procedure. 

    In addition to AAVs and LVs, baculoviral vectors and foamy viral vectors show great potential in a long-term perspective but they only have been researched in preclinical studies. Moreover, herpes simplex viral vectors and adenoviral vectors show potential in cancer treatments or as vaccines rather than in augmentation gene therapy.

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  • 280.
    Ekstrand, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Quality of wildlife damage field inspections and necropsy forms2020Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
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  • 281.
    Ekström, Andreas
    et al.
    Univ Gothenburg, Dept Biol & Environm Sci, Box 463, S-40530 Gothenburg, Sweden..
    Jutfelt, Fredrik
    Norwegian Univ Sci & Technol, Dept Biol, Trondheim, Norway..
    Sundström, L. Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Adill, Anders
    Swedish Univ Agr Sci, Inst Coastal Res, Dept Aquat Resources, Oregrund, Sweden..
    Aho, Teija
    Swedish Univ Agr Sci, Inst Coastal Res, Dept Aquat Resources, Oregrund, Sweden..
    Sandblom, Erik
    Univ Gothenburg, Dept Biol & Environm Sci, Box 463, S-40530 Gothenburg, Sweden..
    Chronic environmental warming alters cardiovascular and haematological stress responses in European perch (Perca fluviatilis)2016In: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology, ISSN 0174-1578, E-ISSN 1432-136X, Vol. 186, no 8, p. 1023-1031Article in journal (Refereed)
    Abstract [en]

    Environmental warming and acute stress increase cardiorespiratory activity in ectothermic animals like fish. While thermal acclimation can buffer the direct thermal effects on basal cardiorespiratory function during chronic warming, little is known about how acclimation affects stress-induced cardiorespiratory responses. We compared cardiovascular and haematological responses to chasing stress in cannulated wild European perch (Perca fluviatilis) from a reference area at natural temperature (16 A degrees C) with perch from the 'Biotest enclosure'; an experimental system chronically warmed (22 A degrees C) by effluents from a nuclear power plant. Routine blood pressure was similar, but Biotest perch had slightly higher resting heart rate (59.9 +/- 2.8 vs 51.3 +/- 2.9 beats min(-1)), although the Q (10) for heart rate was 1.3, indicating pronounced thermal compensation. Chasing stress caused hypertension and a delayed tachycardia in both groups, but the maximum heart rate increase was 2.5-fold greater in Biotest fish (43.3 +/- 4.3 vs 16.9 +/- 2.7 beats min(-1)). Moreover, the pulse pressure response after stress was greater in reference fish, possibly due to the less pronounced tachycardia or a greater ventricular pressure generating capacity and thermally mediated differences in aortic compliance. Baseline haematological status was also similar, but after chasing stress, the haematocrit was higher in Biotest fish due to exacerbated red blood cell swelling. This study highlights that while eurythermal fishes can greatly compensate routine cardiorespiratory functions through acclimation processes, stress-induced responses may still differ markedly. This knowledge is essential when utilising cardiorespiratory variables to quantify and compare stress responses across environmental temperatures, and to forecast energetic costs and physiological constraints in ectothermic animals under global warming.

  • 282.
    Ekström, Emma
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    SPR-based method for concentration determination of proteins in a complex environment2012Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this project a method based on surface plasmon resonance has been developed for determining the concentration of several His-tagged proteins in complex solutions. It showed large dynamic range, no measureable non-specific binding and high sensitivity (with linear range around 0.1–10 μg/ml depending on the proteins). The method showed a low variation when checked on MBP-His during an extended time period. The concentrations of the His-tagged protein in the lysate has also been determined and compared with other alternative methods. This method will later be used to analyse protein concentrations during development and optimization of chromatographic purification process.

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  • 283.
    Elfman, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Chromosome Y Fetal fraction assay2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 284.
    Elgh, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Pterosaur Ichnites from the Late Jurassic of Poland: Morphometrical comparisons with body fossils2018Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 285.
    Elhorst, Paula
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. Institute for Medical Biochemistry and Microbiology (IMBIM).
    Regulation of TGFß signalling by the long noncoding RNA TGFß2-AS12018Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Long noncoding RNAs have been shown to regulate many signalling pathways and their expression has been linked to the development of many cancers. Here we assess the involvement of the long noncoding RNA TGFß2-AS1 in the regulation of the TGFß signalling pathway, specifically its involvement in the TGFß induced process of EMT. In this study, we found that TGFß treatment induced the expression of TGFß2-AS1, and furthermore, TGFß2-AS1 has an inhibitory effect on the expression of the TGFß target genes SERPINE1/PAI-1, CDH2/N-cadherin and Fibronectin. Moreover, our data indicates that TGFß2-AS1 expression has a pro-mitotic effect, that is regulated by PRC2-mediated repression of p15, in HaCaT cells. In conclusion, we show that several EMT markers are differentially regulated by TGFß2-AS1 in response to TGFß and that TGFß2-AS1 plays a role in regulating proliferation.

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  • 286.
    Eliasson, Kajsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Mnemosyne i Sverige: En kvantifiering av artens etablering från 1900-talet till idag2021Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 287.
    Elofsson, Hampus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Immunoassay engineering: An explorative comparison of detection chemestries and surfaces for protein microarrays2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 288.
    Emanuelsson, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Evaluation of River Restoration Measures: Interstitial Habitat Variables and Salmon Hatching Rates as Indicators of Success2023Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    River ecosystems are some of the most complex ecosystems on Earth, characterized by a highly heterogenous environment which is able to sustain a disproportionally high level of biodiversity in relation to the area of which they occupy. However, anthropogenic activities are encroaching on the highly diverse riverine landscape, threatening freshwater biodiversity. Species with complex life cycles involving migrations between marine and freshwater environments are disproportionally threatened. One such species is the Atlantic salmon, which now is at historically low population levels. Restoration efforts are being made to restore degraded river ecosystems and strengthen salmonid populations. However, the response from salmonids and other organisms used as indicators for restoration success are inconclusive or lacking. Additionally, evaluation of restoration success lacks standardized procedures and tools for monitoring. Habitat variables have been shown to be robust indicators when assessing restoration success. This study attempts to asses restoration success using an accessible and user-friendly tool which can be used for measurements of both biotic and abiotic variables. Salmon eggs were planted in the riverbed at potential spawning grounds, from where hyporheic water was extracted to measure physicochemical habitat variables which are critical to salmon embryos. The results indicate that the functionality of available spawning habitats in the study area is adequate in both restored and non-restored sections. Habitat variables displayed spatial variation but were not more favorable at restored sites compared to non-restored sites. Similarly, egg hatching rate varied spatially but not between restored and non-restored sites. The apparent lack of response to the restoration efforts in the study area is likely due to a combination of factors such as biased site selection, limited sampling period and a lack of comparable pre-restoration values. This highlights the need of defined restoration goals, a robust monitoring plan and criteria for evaluation of restoration success. Nevertheless, the method used in this study can be applied to measure biotic and abiotic variables and may add to the toolbox for assessing restoration success. This will hopefully contribute to new insights for monitoring and evaluation of restoration success in other projects.

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  • 289.
    Emil, Vigert
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    An investigation into the role of miR-149 in cutaneous Squamous Cell Carcinoma2022Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Cutaneous squamous cell carcinoma (cSCC) is a cancer of the skin. The leading contributing factor to developing the disease is exposure to ultraviolet radiation (UV) in sunlight. MicroRNAs (miRNAs) are short non-coding RNAs (ncRNAs), responsible for regulating gene expression at the posttranscriptional level. Previous research within the Pivarcsi group has demonstrated that the miRNA miR-149 is downregulated in cSCC. Investigations were made into this miRNA and its target genes in the context of cSCC and the closely related head and neck squamous cell carcinoma (HNSCC). This included searching for putative targets of miR-149 using various prediction methods, and then subjecting these target genes to enrichment analysis. The expression of these miR-149 target genes was also analyzed in a cSCC RNA-Seq dataset produced by the group. Correlation analysis was performed in HNSCC for miR-149 against IFNγ and TGFβ - two suspected regulators of miR-149 expression - and against the miR-149 host gene GPC1. In vitro assays were conducted in two cSCC cell lines: an miR-149 overexpressing cell line against a control cell line, with respect to cell survival, colony formation ability, and chemotherapy agent sensitivity. RT-qPCR was used to test relative expression of genes between the two cell lines. The results revealed that many of the miR-149 target genes were differentially expressed in cSCC compared to healthy skin tissue, and provided insight into cancer-related pathways. Analysis of miR-149 expression in a HNSCC cohort showed that cSCC may differ substantially from HNSCC.

    The full text will be freely available from 2028-01-15 12:00
  • 290.
    Engman, Sarah
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Computational analysis of transcriptional regulation in proximal versus distal normal colon2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Factors involved in transcriptional regulation in the normal colon were investigated computationally. Genes differentially expressed between distal and proximal colon were identified and their promoter structures were analysed for presence of TATA-boxes, CpG islands and transcription factor binding sites. The CpG methylation status of the genes were experimentally verified in colon cancer cell lines and compared between the two groups ofdifferentially expressed genes. A difference in methylation frequency in colon cancer celllines was detected between genes up-regulated and down-regulated in normal proximal colon.

  • 291.
    Engqvist, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    A generic capture assay for immunogenicity, using Biacore2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The purpose of this investigation was to create and optimise a capture assay for the detectionof anti-drug antibodies (ADA) in human plasma, using Biacore. We also dealt with the nonspecificplasma binding to mouse-derived anti-biotin which may occur in the capture assay.By paying attention to these things we aimed at reaching as high sensitivity as possible for theADA detection.

    The capture assay also benefited and gained flexibility from using the same regenerationsolution irrespective of drug and from having a composition that minimises the risk ofdamaging drug epitopes.

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  • 292.
    Engström, Kristina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Understanding the toxic activity and function of CdiA_2 in E. coli R122023Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
  • 293.
    Engström, Mathias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Olby, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Evaluating Response Images From Protein Quantification2020Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Gyros Protein Technologies develops instruments for automated immunoassays. Fluorescent antibodies are added to samples and excited with a laser. This results in a 16-bit image where the intensity is correlated to concentration of bound antibody. Artefacts may appear on the images due to dust, fibers or other problems, which affect the quantification. This project seeks to automatically detect such artifacts by classifying the images as good or bad using Deep Convolutional Neural Networks (DCNNs). To augment the dataset a simulation approach is used and a simulation program is developed that generates images based on developed simulation models. Several classification models are tested as well as different techniques used for training. The highest performing classifier is a VGG16 DCNN, pre-trained on simulated images, which reaches 94.8% accuracy. There are many sub-classes in the bad class, and many of these are very underrepresented in both the training and test datasets. This means that not much can be said of the classification power of these sub-classes. The conclusion is therefore that until more of this rare data can be collected, focus should lie on classifying the other more common examples. Using the approaches from this project, we believe this could result in a high performing product.

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  • 294.
    Engström, Mathias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Pontén, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Philip, Carlsson
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Bahnam, Nadeen
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Strömberg, Ella
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Westlin, Oskar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Antibiotic free and optimised protein production using Escherichia coli2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Affibody® molecules are small therapeutic proteins which mimics antibody functionality. This is a report of several methods for increasing productivity and yield in recombinant production of Affibody® molecules. This literature study shows several steps in the production line which can be optimised, several novel methods for cultivating and harvesting cells and purication of proteins. There is also a section about validation of therapeutic protein production according to The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) are presented.

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  • 295.
    Engzell, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Destruktion av per- och polyfluorerade alkylsubstanser (PFAS) vid förbränning i avfallsförbränningsanläggningar2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Per- and polyfluorinated alkyl substances (PFAS) are a group of environmentally harmful chemicals. The group consists of more than 4730 different substances including two of the most famous ones; PFOA and PFOS. PFAS consist of carbon backbones connected to fluorine. They are in general thermally stable and persistent to degradation due to their C-F bonds, which is one of the strongest bonds in chemistry. The use of PFAS is widespread and therefore they can be found in a variety of consumer products, which eventually end up as waste. Household waste and other waste streams are incinerated at waste incineration facilities at (at least) 850° C for two seconds. The aim of this study was to investigate if that temperature is high enough to, at least partly, break down PFAS and to study where in the outflows PFAS ends up. Three different facilities (B2, P4 and P6) for waste incineration where examined, including incoming fuels; household waste, industrial waste, return fuel and sewage sludge. The three facilities included in the study had two types of boilers (grated and circulating fluidized bed) with three different treatment facilities for the flue gas and condensate. Bottom ash, fly ash, end product and condensate were analysed after incineration. A mass balance based on the limited amount of data indicates that at least 86-98 % of the 11 examined PFAS substances are eliminated. The difference between the three facilities are probably due to a difference in temperature and a few problems during the sample week. Another reason might be the variations in PFAS concentrations in incoming fuels. The facility with the lowest elimination percentage also had the lowest PFAS-concentrations in incoming fuels, and some problems during the sample period. The facility with the highest elimination percentage had a more even and higher temperature.

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  • 296.
    Epremidze, Dali
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    The neuropeptide catestatin's inhibitory properties in macrophages through the alpha7 nAChR pathway and its effects on pancreatic islet compositions2023Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Our study aimed to investigate the potential role of Catestatin (CST) neuropeptide, derived from chromogranin A (CgA), in neuroimmune communications and pancreatic islet development. We hypothesized that CST acts as a neurotoxin as it can inhibit neural cells through the nicotine acetylcholine receptor (nAChR), although the precise mechanism remains unknown. To test this hypothesis, we performed sequence alignments comparing CST with alpha-bungarotoxin (α-BGT) and its related neurotoxins, a known nAChR inhibitor, to identify any sequence similarities. Additionally, we aligned and visualized the structures of CST and α-BGT bound to nAChR to explore potential interactions. Furthermore, given the high conservation of nAChR through species, we hypothesized that CST might influence the α-7 nAChR in macrophages similarly to neural cells. To verify this, we conducted western blot analyses to confirm the presence of α-7 nAChR in macrophages. We then assessed the effects of CST on macrophages by measuring TNF-α levels using an enzyme-linked immunosorbent assay (ELISA). Another aspect of our research focused on examining the physiological impact of CST and CgA on pancreatic islet development. We stained tissue samples from catestatin knockout (CST-KO), chromogranin A knockout (CgA-KO), and wild-type (WT) mice pancreas and analyzed the resulting compositional changes in the islets.

    According to the results, CST shares part of the binding regions with α-BGT and its related neurotoxins. In macrophages, CST demonstrated inhibitory properties, as evidenced by increased TNF-α levels, comparable to the effects observed with our control α-BGT. The absence of CgA affected islet density and circularity in comparison to the WT. Notably, the knockout of both CgA and CST resulted in an increase in glucagon-producing alpha cells and a decrease in insulin-producing cells.

    In conclusion, our study suggests that CST may play a crucial role in neuroimmune communications, exerting inhibitory effects on macrophages via the α7 nAChR, akin to its action on neural cells. Additionally, CST may influence the normal development of islet composition.

  • 297.
    Erdélyi, András
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    HisA mutants with minor structural differences display major functional deviations2016Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Even though enzymes tend to specialize on one reaction during evolution, enzyme promiscuity is an abundant phenomenon. The subject of this thesis is the Salmonella enterica N’-[(5’-phosphosoribosyl)-formimino]-5-aminoimidazole-4 carboxamide-ribonucleotide (ProFAR) isomerase (SeHisA), a (βα)8-barrel enzyme from the histidine biosynthesis that catalyzes one reaction on one substrate in one organism. In Actinobacteria HisA has evolved to a bifunctional enzyme called phosphoribosyl isomerase A (PriA): it is capable of catalyzing the reaction normally done by the N’-(5’-phosphoribosyl) anthranilate (PRA) isomerase (TrpF) as well. The functional plasticity of PriA is possible due to the common reaction mechanism of HisA and TrpF, called Amadori rearrangement. The Amadori rearrangement is an acid-base catalyzed isomerization reaction where the aminoaldose (ProFAR or PRA) is converted into the corresponding ketose (PRFAR or CdRP). A SeHisA mutant with a glutamine to arginine mutation in position 18 (Q18R) shows a detectable TrpF activity, whereas another mutant with a duplication of residues from 13 to 15 (dup13-15) loses its HisA activity and gains TrpF activity.

    My first aim was to improve the TrpF activity of the Q18R mutant. A G79S mutation was introduced inspired by PriA. Proteins were purified and crystallized. In order to gain complex structures with either the TrpF reaction product analogue reduced CdRP (rCdRP) or ProFAR, co-crystallization and soaking were done. ProFAR is not commercially available and had to be synthetized and purified. In vitro TrpF activities of the Q18R and Q18R/G79S mutants were measured. My second aim was to compare the Q18R mutant with the dup13-15 mutant, since there is very little structural difference between them, but they show high difference in catalytic activity. Mutants, which would bridge the functional gap between them, were designed and by using lambda red recombineering were introduced into a Salmonella typhimurium genome. In vivo growth rate was measured and relative fitness was calculated for each mutant in respect to their HisA and TrpF activity.

    HisA mutants Q18R and Q18R/G79S showed very poor TrpF activity in in vitro assays. No dissociation constants could be measured for either of the mutants using microscale thermophoresis, and a very low kcat/KM value (~2 s-1M-1) with a high error rate could be determined for Q18R/G79S. Complex structures of Q18R and Q18R/G79S mutants with ProFAR were solved at a 2.47 Å and a 1.78 Å, respectively, from soaked crystals. No structure with rCdRP was obtained. Growth rate measurements in comparison with a strain with wild type HisA and TrpF, gave striking results pointing out the important role of the residue in the position 16 when three residues are inserted after the arginine in position 18. A leucine in position 16 yielded wild type HisA activity (94%) and poor TrpF activity (0-5%), with a valine, no HisA activity (0%) and a moderate TrpF activity (38-46%) were found compared to the wild type. These results pointed out how small the barrier between a specialist, a promiscuous and a bifunctional enzyme can be. SeHisA, being a specialized enzyme can easily be modified in order to gain TrpF function, and as I have showed in the present study, a single methyl group (the difference between a leucine and a valine) can turn the activity of an enzyme inside out.

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    Master thesis_András Erdélyi_2016
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  • 298.
    Ericsson, Hedda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Selaginella - phylogeny of the South American species within subgenus Stachygynandrum2023Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Selaginellaceae is a family within the lycophytes, and it comprises one genus, Selaginella. They are herbaceous seedless vascular plants found globally, with around 750 species. Selaginella is divided into several subgenera, but there is no classification that is agreed upon. This thesis is based on one of these classifications (Weststrand & Korall, 2016a,b). The subgenus Stachygynandrum is the most species rich from that study. Within the subgenus is an unresolved clade of South American species. The aim of this study is to contribute to resolve the phylogeny of that clade. A phylogenetic analysis using Bayesian inference was used on the chloroplast regions atpB, rbcL-atpB intergenic spacer and psbE-petL intergenic spacer. These have previously never been used for studies on the Selaginella phylogeny. New primers were constructed for these regions. The datasets from all three regions were also concatenated. This study’s data was also combined with data from Weststrand and Korall (2016b). There were successful amplifications of all new regions, but most specimens failed to be amplified. The phylogenies from the new three regions are mostly in agreement with the one presented by Weststrand & Korall (2016b). The clade splits into two larger groups. Some branch support differ between this study and the previous study. The position of S. huehuetenangensis was resolved in this study as a sister group to S. reflexa and S. apoda, with a posterior probability of 1. Two specimens identified as S. umbrosa are on different branches in the tree. 

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  • 299.
    Eriksson, Alexandra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    The internationalization of new technology within an organization with unclear ownership2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This master thesis was done at Uppsala Clinical Research Center (UCR). UCR have recently developed the technical platform QReg 5 for managing quality registries. UCR have been in contact with several international organizations interested in collaborating with UCR because of their expertise within quality registries as well as their technical competence. UCR have a complicated owner structure as well as organizational structure, as they are owned by Uppsala University and Uppsala County Council. The purpose of this master thesis was to present how QReg 5 could be commercialized under UCR's preconditions. In order for the internationalization plans to be successful, it was shown that the shared ownership of UCR needs to become clearer. By taking advantage of the possibilities with the new development section at UCR, the management of the contacts will be more efficient. Potential competitors for UCR are registry centers that have created their own technical solutions, large software companies, Life Science related organizations (e.g. hospitals), the organizations that UCR license QReg 5 to, as well as software companies creating electronic medical records. The most interesting customer segment for UCR are organizations with technical competences, which are placed in countries were quality registries are not yet in use. 

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  • 300.
    Eriksson, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. Anna Eriksson.
    Evaluation of artificially dead wood for nature restoration: comparison of insect and woodpecker activity between ring-barked and naturally dead birches (Betula spp.)2022Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Intensive land use with resulting reduction and loss of habitats is one of the reasons behind the loss of biodiversity that the world is currently facing. In Sweden, natural forests are scarce today because of intensive forestry, which has led to a decline in many forest habitats, such as dead wood. One organism that has been heavily affected by loss of habitat is the white-backed woodpecker. This bird prefers deciduous forests rich in dead wood and more than 200 threatened species of insects and other organisms also prefer this habitat. For this reason the white-backed woodpecker is considered an umbrella species. In order to restore deciduous forests rich in dead wood and thereby favor species depending on this, dead deciduous wood is created artificially, often by ring-barking. Studies of artificially created deciduous dead wood are still largely lacking. The aim of this study is to contribute to research in deciduous forests by comparing ring-barked birches to naturally dead birches in terms of density of insect holes and woodpecker foraging activity (in general, not of a certain species). Insect holes were counted up to 2.2 meters and woodpecker foraging activity was scored on a scale from 1 - 5 on 144 ring-barked and 132 naturally dead birches across six sites in Uppland, Västmanland and Gästrikland, Sweden. Ring-barked birches did not have as many insect holes/surface area as did naturally dead trees and this differed between sites. Woodpecker foraging activity, on the other hand, did not differ between the dead wood categories but differed between sites. Further, both density of insect holes and woodpecker foraging activity increased with the diameter of the trees and woodpecker foraging activity also increased with number of insect holes/surface area across both dead wood categories. The results suggest that ring-barked birches do not fully mimic naturally dead birches when it comes to insect abundance but woodpeckers forage on ring-barked birches to a similar extent as on naturally dead birches. Thus, ring-barking of birches does not fully replace naturally dead wood of birch but it can serve as an important complement. 

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