Expression of the FGFR2c mesenchymal splicing variant in human keratinocytes inhibits differentiation and promotes invasion

The altered isoform switching of the fibroblast growth factor receptor 2 (FGFR2) and aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells is involved in cancer progression. We have recently described that the ectopic expression of FGFR2c in normal human keratinocytes induces epithelial-mesenchymal transition and leads to invasiveness and anchorage-independent growth. Here, we extended our analysis to the effects of this FGFR2c forced expression on human keratinocyte differentiation and stratification. Our findings demonstrated that, differently from cells overexpressing the epithelial splicing variant FGFR2b, keratinocytes ectopically expressing FGFR2c are not able to form a monolayer and display decreased expression of early differentiation markers. This impaired ability to enter the differentiation program is related to the up-modulation of the transcription factor ΔNp63. In addition, FGFR2c-expressing keratinocytes undergo defective stratification and invasion of the collagen matrix in 3D organotypic cultures, further suggesting their tumorigenic potential. Taken together, our results support the hypothesis that the receptor switching and the consequent appearance of the mesenchymal FGFR2c variant in the epithelial context would drive early steps of carcinogenesis, unbalancing the p63/FGFR interplay, and altering the paracrine response to the microenvironment

Taxonomic studies on adult and larval ascidians from California

The primary purpose of this research is to further morphological studies on larval ascidians and to encourage greater reliance on larval structures in ascidian taxonomy. This may necessitate some revisions in current classifications, but it is hoped that such revisions will lead to a better understanding of the group. Some general considerations of ascidians are here included for the benefit of those who may not be familiar with them. All specimens used in this study were collected at the Pacific Marine Station area at Dillon Beach, California, during June, July, and August of 1957

Offshore Wind Farm Layouts: Performance Comparison for a 540 MW Offshore Wind Farm

This master thesis has been written at the Department of Electric Power Engineering at the Norwegian University of Science and Technology. The work has been carried out at the Royal Institute of Technology in Stockholm, where the author spent the last year of his studies as an exchange student. In the thesis, six different designs of the electrical grid of a 540 MW offshore wind farm, placed 100km off the Norwegian coast, have been studied and compared. At this distance, AC cable transmission might be difficult because of the reactive power production in the cables. Taking this into consideration, two options for the transmission system to shore have been studied. In addition to the AC cable transmission, voltage source converter based HVDC transmission, in the form of HVDC Light, has been studied, giving a total of 12 models. The main scope of the thesis was to study the load flow situation and power system performance of the different offshore wind farm layouts. Two load flow cases were run for each model; the first studying the model when the active power transmission to shore was maximized, the second studying the model under a contingency situation. The reliability of the six designs was compared by calculating the expected number of cable failures during the life time of the wind farm for each design, and what consequence the disconnection of any cable would have on the power losses. In order to study the effect of the offshore grid design and transmission system design on the offshore power system stability, dynamic simulations have also been executed, and the voltage response and rotor speed response following a fault have been studied. All simulations have been executed in version 31 of the program PSS/E. The wind farm was modeled full scale, consisting of 108 wind turbines rated at 5MW. The wind turbines were modeled as doubly fed induction generators, using the generic wind model that comes with the program. The load flow simulations showed that an AC cable connection to shore gave lower total system losses than a DC connection for all designs. The lowest losses were found at the n-sided ring design in the AC/AC system, and the highest losses were found for the star design in the AC/DC system. These losses were 2.33% and 8.19% of the total installed capacity, respectively. In the dynamic simulations, a three phase short circuit fault, lasting 150ms, was applied at three different places in the system. The simulations showed that except from at the wind turbines that were islanded as a result of a fault, all dynamic responses were stable. The HVDC Light transmission to shore gave the highest voltage drops and the lowest voltage peaks offshore. Also, the maximum speed deviation was found to be larger when using HVDC Light transmission compared to using AC cables, with two exceptions; the radial and star designs when a fault was applied to the transmission system. A comparison of the six different grid designs showed that the results were varying. Based on the results in this thesis it has not been concluded that one of the offshore designs have better dynamic qualities than the other. The simulation results indicated that this is case specific, and more dependent on where in the offshore grid the fault occurs rather than the design of the offshore grid

Hvilken betydning har kontekst i matematikkoppgaver : et studie av matematikkoppgaver i PISA-undersøkelsen

Hvilken betydning har kontekst i matematikkoppgaver? Et studie av matematikkoppgaver i PISA-undersøkelsen. Hovedoppgaven tar utgangspunkt i matematikkoppgavene fra PISA-undersøkelsen, hvor enkelte av oppgavene er svært dårlig besvart. Er det slik at norske elever er svake i matematikk, eller kan det være noe med presentasjonen av oppgavene som gjorde at de norske elevene synes oppgavene var vanskelig. I hovedoppgaven sammenlignes resultater fra PISA-undersøkelsen med en undersøkelse foretatt på 112 elever fra 10. klasse

Intracellular trafficking of FGF1 endocytosed by its four tyrosine kinase receptors

Fibroblast growth factors and the four related high-affinity, tyrosine kinase fibroblast growth factor receptors are involved in the regulation of many key cellular responses in developmental and physiological processes. Irregularities in FGF-mediated signalling are implicated in several serious disorders such as cancer and various forms of dwarfism. Little is known about the fate of endocytosed fibroblast growth factors and their receptors and the main purpose of this project is to study and compare the intracellular trafficking of the fibroblast growth factor 1 and the four related tyrosine kinase fibroblast growth factor receptors upon internalization

Landscape and Rock Art. An archaeological landscape analysis regarding the distribution of rock art in Onsøy, Fredrikstad

This study analyses and discusses the distribution and placement of Bronze Age rock art localities in Onsøy, Fredrikstad. The preliminary focus is on the rock art localities’ relationship with the surrounding landscape, and how the distribution can be understood in relevance to the social life of Onsøy’s prehistoric population. The overall premise for this thesis is that rock art has emerged in a ritual or cosmological setting. However, the intent of the study is to present a deeper understanding of how rock art also represented an active social role in the prehistoric society of Onsøy. The study takes advantage of digital methods to investigate the rock art’s placement in the landscape, including predictive modelling, viewshed analysis, and cost-affordance analysis. By adding the two latter methods in addition to reconstructing the prehistoric landscape, a post-processual landscape view will be considered, focusing on perception. The results show that Bronze Age rock art is closely connected to the prehistoric coastline and communication paths in the landscape. The results also indicate that the localities in large are placed on low occurrences of bedrock, with low visibility in the holistic landscape. Therefore, I argue that the distribution of rock art localities in Onsøy can be seen as a manifestation of social memory, social identity and transmission of knowledge connected to prehistoric communication.Arkeologi mastergradsoppgaveARK35

Samarbeid mellom barnevernsinstitusjoner og psykisk helsevern for barn og unge: En kvalitativ studie av ansatte på Frelsesarmeen sine barnevernsinstitusjoners erfaringer om samarbeidet med psykisk helsevern for barn og unge

Oppgavens tema er samarbeid mellom barnevernsinstitusjoner og psykisk helsevern for barn og unge (PHBU). Samarbeidets aktualitet i media er med på å vise viktigheten av å forske på dette temaet. Temaet er avgrenset til følgende problemstilling: "Hvordan erfarer ansatte i Frelsesarmeen sine barnevernsinstitusjoner samarbeidet med PHBU? Hvilke føringer og barrierer finnes i samarbeidet?”. For å belyse temaet er det blitt gjennomført syv individuelle kvalitative livsformsinstervjuer, blant ansatte på Frelsesarmeen sine barnevernsinstitusjoner. Deretter er det gjennomført en datadreven tematisk analyse av empirien. Det første funnet omhandler å finne en felles forståelse for hvordan de ansatte på barnevernsinstitusjoner skal tilnærme seg barna på institusjonen. Det andre funnet handler å danne en felles forståelse av hvordan PHBU skal tilnærme seg personale og barna på institusjonen. Disse funnene fortolkes i lys av Dag. G. Aaslands (2014) teori om å finne en felles forståelse av samarbeidets «objekt». Det tredje funnet handler om de ansattes behov for gjensidig anerkjennelse av kunnskap i samarbeidet. Dette funnet fortolkes i lys av Aaslands (2014) teori om dannelse av "vi-subjektet" i samarbeidet. Informantenes erfaringer med å finne felles forståelse av «samarbeidets objekt» og dannelse av «vi-subjeket» i samarbeidet, diskuteres videre i lys av tidligere forskning, og rammebetingelser for samarbeidet. Rammebetingelsene innebærer litteratur om «ny offentlig styring» sin innvirkning på helse og sosialfaglig praksis og miljøterapi som behandlingsform på barnevernsinstitusjoner. Tidligere forskning bidrar til å underbygge de ansatte sine erfaringer, med å finne en felles forståelse av samarbeidets objekt og dannelse av «vi-subjekt» i samarbeidet. Diskusjonen av rammebetingelsene bidrar til å underbygge viktigheten av fleksibilitet og annerkjennelse av miljøterapi i samarbeidet. I tilegg kommer det frem hvilke begrensinger «ny offentlig styring» setter for dette

Exposure to Particulate Matter and Respirable Crystalline Silica in Tunnel Construction Workers Using Tunnel Boring Machines

Objectives This study aimed to assess the exposure to a selection of aerosols and gases in the work environment for workers performing tunnel construction using tunnel boring machines (TBMs), to identify determinants of exposure based on the information available and to calculate robust estimates of exposure using a statistical model. The focus was particulate matter (PM) and respirable crystalline silica (RCS). In addition, concentrations of nitrogen dioxide (NO2), elemental carbon (EC), and oil mist were assessed. Methods Personal sampling was conducted from February 2017 to February 2019. PM in the thoracic and the respirable aerosol fractions was collected, and RCS was determined in the respirable aerosol fraction. Context information was collected on questionnaires. Because the workers could participate in the sampling more than once and multiple measurements were performed on the same date a mixed model was used in the analysis. Concentrations of PM and RCS are presented as estimated and measured geometric means (GMest and GMmea) and estimated arithmetic mean (AMest) in addition to the median. Measured concentrations of NO2, EC, and oil mist are presented as geometric means. Results A total of 290 and 289 personal samples of PM in the thoracic and respirable aerosol fractions were available for analysis, respectively. Work title/work location, type of work (production, maintenance, or a combination of the two), and date of sampling were identified as determinants of exposure. Workers in the front of the TBMs had the highest exposure to PM and RCS. The GMest of RCS exposure varied from 35 to 413 μg m–3 depending on the work title. The geometric standard deviations for measured RCS concentrations by work title ranged from 1.6 to 3.5. A total of 16 samples of NO2 and EC and 12 samples of oil mist were collected. Maximum values of NO2 and EC were 54 µg m–3 and 23 µg m–3, respectively. The maximum measured value of oil mist was 0.08 mg m–3. Conclusions All TBM workers were exposed to PM and RCS. Exposure to RCS may be substantial, and workers in front of the TBM were exposed to the highest concentrations of both PM and RCS. A day-to-day variation was found, probably caused by differences in drilling activities. Preventive measures are warranted to keep the exposure to PM and consequently the exposure to RCS as low as possible to protect the health of workers in tunnel construction.Exposure to Particulate Matter and Respirable Crystalline Silica in Tunnel Construction Workers Using Tunnel Boring MachinespublishedVersio

Interplay between estrogen receptor and AKT in estradiol-induced alternative splicing.

BACKGROUND: Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. METHODS: MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. RESULTS: We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERα cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERα binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERα and splicing factors, influenced ERα:E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ERα-dependent overexpression of FGFR2, whereas resistance to fulvestrant was associated with ERα-dependent isoform switching, which correlated with altered response to KGF. CONCLUSION: E2 may partly alter cellular proteome through alternative splicing uncoupled to its effects on transcription initiation and aberration in E2-induced alternative splicing events may influence response to anti-estrogens.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Myocardial oxidative stress is increased in early reperfusion, but systemic antioxidative therapy does not prevent ischemia-reperfusion arrhythmias in pigs

BackgroundArrhythmias in the early phase of reperfusion after myocardial infarction (MI) are common, and can lead to hemodynamic instability or even cardiac arrest. Reactive oxygen species (ROS) are thought to play a key role in the underlying mechanisms, but evidence from large animal models is scarce, and effects of systemic antioxidative treatment remain contentious.MethodsMI was induced in 7 male and 7 female pigs (Norwegian landrace, 35–40 kg) by clamping of the left anterior descending artery (LAD) during open thorax surgery. Ischemia was maintained for 90 min, before observation for 1 h after reperfusion. Pigs were randomized 1:1 in an operator-blinded fashion to receive either i.v. N-acetylcysteine (NAC) from 70 min of ischemia and onwards, or 0.9% NaCl as a control. Blood samples and tissue biopsies were collected at baseline, 60 min of ischemia, and 5 and 60 min of reperfusion. ECG and invasive blood pressure were monitored throughout.ResultsThe protocol was completed in 11 pigs. Oxidative stress, as indicated by immunoblotting for Malondialdehyde in myocardial biopsies, was increased at 5 min of reperfusion compared to baseline, but not at 60 min of reperfusion, and not reduced with NAC. We found no significant differences in circulating biomarkers of myocardial necrosis, nor in the incidence of idioventricular rhythm (IVR), non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT) or ventricular fibrillation (VF) between NAC-treated and control pigs during reperfusion.ConclusionMyocardial oxidation was increased early after reperfusion in a porcine model of MI, but systemic antioxidative treatment did not protect against reperfusion arrhythmias