Article Nine of Japan’s Constitution: From Renunciation of Armed Force “Forever” to the Third Largest Defense Budget in the World

Each year approximately 2,000 new detailed development plans are accepted in Sweden. When an area is covered by a new detailed development plan, it is often necessary that land has to be acquired to adjust the property units to the new plan. The owner conditions of the property units can usually be adjusted through negotiations between the seller and the buyer. But in some situations, when no agreements can be reached, it is possible to use coercive measures to purchase the land. Compulsory purchases are only permitted when certain legal criteria’s are met. The legal ability of compulsory purchases also affects voluntary negotiations since they function as "game rules". The compensations that are given in compulsory purchases then functions as a sort of minimum level of the compensations given in voluntary negotiations. The purpose of this thesis is to study the compensation that should be given in different situations when land is being compulsory purchased. Furthermore, the purpose is also to study the motives behind the legislation regarding compulsory purchases. In order to find an answer to the purpose of this thesis, a study has been made with a representative property unit. In the study, land was taken with coercive measures in four different situations from the property unit when a new detailed development plan covered the property unit. The four different situations were chosen to illustrate the differences between the given compensations. In the four different situations two different legal systems were applied. First, the existing legal system in Sweden was applied and then an alternative system based on principles that earlier could be found in the, now no longer existing, Act regarding development cooperation units (SFS 1987:11, lag om exploateringssamverkan) was applied. The result of the study shows that the compensation given depends upon the allowed land use in the new detailed development plan and upon which legal system that is applied. In the current Swedish legal system, the allowed land use for the specific property unit in the detailed development plan had the largest impact on the compensation given. In the alternative system, the total allowed land use in the detailed development plan was of importance for the given compensation together with what the property owner had contributed to the development area.Varje år antas cirka 2000 detaljplaner i Sverige. När ett område detaljplaneläggs behöver mark vanligtvis förvärvas för att anpassa fastigheterna till de nya förhållandena. Ägarförhållandena kan vanligtvis anpassas via förhandlingar mellan köpare och säljare. Men i vissa situationer, om ingen överenskommelse kan nås, är det tillåtet att använda tvångsregler för att förvärva marken. Tvångsreglerna får bara användas när kriterier uppställda i lagen är uppfyllda. Även vid frivilliga förhandlingar fyller tvångsreglerna en funktion eftersom de då fungerar som spelregler. Lagstiftningens ersättningsbestämmelser utgör en slags miniminivå för ersättningens storlek. Syftet med denna uppsats är dels att studera vilken ersättning som betalas i olika situationer när mark tvångsförvärvas inom detaljplanelagt område och dels att studera de motiv som ligger till grund för lagstiftningens utformning. För att besvara syftet har en typfallsstudie genomförts där mark frångick en typfastighet för fyra olika markåtkomstsituationer när en ny detaljplan blev gällande över området. Situationerna valdes för att tydliggöra att ersättningen som utgår vid olika markåtkomstsituationer kan variera. I studien tillämpades både dagens ersättningssystem samt ett konstruerat ersättningssystem som baserades på den upphävda lagen om exploateringssamverkan (ESL). Framkomna resultat visar att ersättningen kan variera dels beroende av vad marken ska användas till och dels beroende av vilket ersättningssystem som tillämpas. I det nu gällande ersättningssystemet är den största påverkan på ersättningen vad marken får användas till enligt detaljplanen. I det alternativa ersättningssystemet är det detaljplanens totala utformning som styr ersättningsbeloppet tillsammans med vad respektive fastighetsägare bidragit med till planområdet

The roles of MS2 RNA in MS2 capsid assembly

Single strand (ss) RNA viruses are amongst the most prevalent viral pathogens in nature. A key event in the life cycle of many of these viruses is the packaging of their ssRNA genome into a capsid of defined size and shape. The mechanism by which genome packaging and capsid assembly proceeds is however poorly understood. Increased knowledge of this event is beneficial for novel anti-viral drug design, as well as contributing to our understanding of macromolecular assembly events. This project has explored the role(s) of the RNA genome in the capsid assembly process of the model ssRNA virus, bacteriophage MS2. In vitro capsid reassembly reactions have been carried out using recombinant coat protein and ssRNA transcripts corresponding to different regions of the MS2 genome. These reactions have been assayed by size distribution analysis using native gel shift assays and sedimentation velocity analysis. This has allowed the effects of RNA size, sequence and structure on capsid assembly to be investigated. All the genomic RNAs transcripts, independent of sequence and size, promoted capsid assembly. The efficiency in which they each promote assembly was, however, different. This was shown to be due to the mechanism by which genomic RNA is packaged. It appears that coat proteins bind to RNA causing conformational changes that reduce its volume to that of the capsid interior. This was evident from the observed RNA length dependence on capsid assembly efficiency. Estimates of the hydrodynamic radii of assembly components and the inhibitory effect that ethidium bromide, a compound which stiffens RNA structure, has on capsid formation also supported this hypothesis. The RNA structural transition was investigated using an RNA structure probing assay. The solution structures of the RNA transcripts were compared to the MS2 genome structure within the virion. Lead acetate was used to cause structure-specific cleavages within these RNAs which were then detected by reverse transcription using labelled primers. The results show that the RNA structure is partly conserved in solution and within the virion, implying that the conformational changes during encapsidation involve primarily tertiary structure rearrangement. The data suggest that the MS2 virion RNA has a defined structure within the virion. These results are consistent with cryo-electron microscopy of virions and capsids carried out by other members of the laboratory. One implication of this work is that compounds capable of inhibiting the conformational rearrangements required for virus assembly could serve as potent anti-viral therapeutics. The work presented in this thesis has contributed to our understanding of how ssRNA is packaged into ssRNA virus capsids and, in particular, the roles it plays in capsid assembly

Höga krav och stress i vardagen - Gymnasieungdomars upplevelse av utbildning, aktivitetsbalans och hälsa

Bakgrund: Ökningen av ungas psykiska ohälsa är ett växande folkhälsoproblem och skolrelaterad stress är vanligt förekommande bland ungdomar på gymnasiet. Ur hälsosynpunkt har skolan det yttersta ansvaret för ungas utveckling och deras huvuduppgift är att hjälpa eleverna att nå kunskapsmålen. I dagsläget är forskning kring ungas aktivitetsbalans samt effektiviteten av arbetsterapeutiska interventioner bland gymnasieungdomar i Sverige begränsad. Syfte: Syftet var att beskriva gymnasieungdomars självskattade upplevelser av utbildning samt av aktivitetsbalans och hälsa i vardagen. Metod: Webbaserad enkät användes som kvantitativ datainsamlingsmetod och analyserades genom deskriptiv statistik. Resultat: Resultatet visade att gymnasieungdomarna upplever obalans mellan vardagens aktiviteter samt stress i skolan respektive i vardagen. Resultatet visade även att gymnasieungdomarna upplevde svårigheter i både tidigare och nuvarande skolgång, i kombination med höga krav, och att det finns ett behov av ökat stöd i skolan. Slutsats: Arbetsterapi, som en stödjande resurs, kan med sitt specifika tänk kring samspelet mellan person, miljö och aktivitet arbeta hälsofrämjande med elever och lärare i den svenska skolvärlden

Elucidating dynamic metabolic physiology through network integration of quantitative time-course metabolomics.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.The increasing availability of metabolomics data necessitates novel methods for deeper data analysis and interpretation. We present a flux balance analysis method that allows for the computation of dynamic intracellular metabolic changes at the cellular scale through integration of time-course absolute quantitative metabolomics. This approach, termed "unsteady-state flux balance analysis" (uFBA), is applied to four cellular systems: three dynamic and one steady-state as a negative control. uFBA and FBA predictions are contrasted, and uFBA is found to be more accurate in predicting dynamic metabolic flux states for red blood cells, platelets, and Saccharomyces cerevisiae. Notably, only uFBA predicts that stored red blood cells metabolize TCA intermediates to regenerate important cofactors, such as ATP, NADH, and NADPH. These pathway usage predictions were subsequently validated through (13)C isotopic labeling and metabolic flux analysis in stored red blood cells. Utilizing time-course metabolomics data, uFBA provides an accurate method to predict metabolic physiology at the cellular scale for dynamic systems.National Heart Lung and Blood Institute European Research Council U.S. Department of Energ

Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesEndothelial dysfunction contributes to sepsis outcome. Metabolic phenotypes associated with endothelial dysfunction are not well characterised in part due to difficulties in assessing endothelial metabolism in situ. Here, we describe the construction of iEC2812, a genome scale metabolic reconstruction of endothelial cells and its application to describe metabolic changes that occur following endothelial dysfunction. Metabolic gene expression analysis of three endothelial subtypes using iEC2812 suggested their similar metabolism in culture. To mimic endothelial dysfunction, an in vitro sepsis endothelial cell culture model was established and the metabotypes associated with increased endothelial permeability and glycocalyx loss after inflammatory stimuli were quantitatively defined through metabolomics. These data and transcriptomic data were then used to parametrize iEC2812 and investigate the metabotypes of endothelial dysfunction. Glycan production and increased fatty acid metabolism accompany increased glycocalyx shedding and endothelial permeability after inflammatory stimulation. iEC2812 was then used to analyse sepsis patient plasma metabolome profiles and predict changes to endothelial derived biomarkers. These analyses revealed increased changes in glycan metabolism in sepsis non-survivors corresponding to metabolism of endothelial dysfunction in culture. The results show concordance between endothelial health and sepsis survival in particular between endothelial cell metabolism and the plasma metabolome in patients with sepsis.RANNIS Landspitali Reykjavik Rigshospitalet Copenhage

EMT-derived alterations in glutamine metabolism sensitize mesenchymal breast cells to mTOR inhibition

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by American Association for Cancer Research in Molecular Cancer Research on 04/06/2021.Available online: https://mcr.aacrjournals.org/content/19/9/1546acceptedVersio

Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesEpithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination.Icelandic Research Counci

Current Status and Future Prospects of Genome-Scale Metabolic Modeling to Optimize the Use of Mesenchymal Stem Cells in Regenerative Medicine.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMesenchymal stem cells are a promising source for externally grown tissue replacements and patient-specific immunomodulatory treatments. This promise has not yet been fulfilled in part due to production scaling issues and the need to maintain the correct phenotype after re-implantation. One aspect of extracorporeal growth that may be manipulated to optimize cell growth and differentiation is metabolism. The metabolism of MSCs changes during and in response to differentiation and immunomodulatory changes. MSC metabolism may be linked to functional differences but how this occurs and influences MSC function remains unclear. Understanding how MSC metabolism relates to cell function is however important as metabolite availability and environmental circumstances in the body may affect the success of implantation. Genome-scale constraint based metabolic modeling can be used as a tool to fill gaps in knowledge of MSC metabolism, acting as a framework to integrate and understand various data types (e.g., genomic, transcriptomic and metabolomic). These approaches have long been used to optimize the growth and productivity of bacterial production systems and are being increasingly used to provide insights into human health research. Production of tissue for implantation using MSCs requires both optimized production of cell mass and the understanding of the patient and phenotype specific metabolic situation. This review considers the current knowledge of MSC metabolism and how it may be optimized along with the current and future uses of genome scale constraint based metabolic modeling to further this aim.Icelandic Research Fund Institute for Systems Biology's Translational Research Fellows Progra

Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2) Is Upregulated in Breast Epithelial-Mesenchymal Transition and Responds to Oxidative Stress

Funding Information: com. This work was funded by Icelandic Center for Research (RANNÍS, 163254-052) and Göngum Saman 2018. Funding Information: We are grateful for the contributions from Douglas Lamont and Amy Tavendale at the "Finger- Prints" Proteomics Facility, College of Life Sciences, MSI/ WTB/JBC Complex, University of Dundee, for their help with the proteomic and phosphoproteomic data collection and analysis. The graphical abstract was created with BioRender.com. This work was funded by Icelandic Center for Research (RANNIS, 163254-052) and Göngum Saman 2018. Publisher Copyright: © 2021 THE AUTHORS.Breast cancer cells that have undergone partial epithelial- mesenchymal transition (EMT) are believed to be more invasive than cells that have completed EMT. To study metabolic reprogramming in different mesenchymal states, we analyzed protein expression following EMT in the breast epithelial cell model D492 with single-shot LFQ supported by a SILAC proteomics approach. The D492 EMT cell model contains three cell lines: the epithelial D492 cells, the mesenchymal D492M cells, and a partial mesenchymal, tumorigenic variant of D492 that overexpresses the oncogene HER2. The analysis classified the D492 and D492M cells as basal-like and D492HER2 as claudin-low. Comparative analysis of D492 and D492M to tumorigenic D492HER2 differentiated metabolic markers of migration from those of invasion. Glutamine-fructose-6- phosphate transaminase 2 (GFPT2) was one of the top dysregulated enzymes in D492HER2. Gene expression analysis of the cancer genome atlas showed that GFPT2 expression was a characteristic of claudin-low breast cancer. siRNA-mediated knockdown of GFPT2 influenced the EMT marker vimentin and both cell growth and invasion in vitro and was accompanied by lowered metabolic flux through the hexosamine biosynthesis pathway (HBP). Knockdown of GFPT2 decreased cystathionine and sulfide: quinone oxidoreductase (SQOR) in the transsulfuration pathway that regulates H2S production and mitochondrial homeostasis. Moreover, GFPT2 was within the regulation network of insulin and EGF, and its expression was regulated by reduced glutathione (GSH) and suppressed by the oxidative stress regulator GSK3-β. Our results demonstrate that GFPT2 controls growth and invasion in the D492 EMT model, is a marker for oxidative stress, and associated with poor prognosis in claudin-low breast cancer.Peer reviewe

Analyzing Metabolic States of Adipogenic and Osteogenic Differentiation in Human Mesenchymal Stem Cells via Genome Scale Metabolic Model Reconstruction.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadSince their initial discovery in 1976, mesenchymal stem cells (MSCs) have been gathering interest as a possible tool to further the development and enhancement of various therapeutics within regenerative medicine. However, our current understanding of both metabolic function and existing differences within the varying cell lineages (e.g., cells in either osteogenesis or adipogenesis) is severely lacking making it more difficult to fully realize the therapeutic potential of MSCs. Here, we reconstruct the MSC metabolic network to understand the activity of various metabolic pathways and compare their usage under different conditions and use these models to perform experimental design. We present three new genome-scale metabolic models (GEMs) each representing a different MSC lineage (proliferation, osteogenesis, and adipogenesis) that are biologically feasible and have distinctive cell lineage characteristics that can be used to explore metabolic function and increase our understanding of these phenotypes. We present the most distinctive differences between these lineages when it comes to enriched metabolic subsystems and propose a possible osteogenic enhancer. Taken together, we hope these mechanistic models will aid in the understanding and therapeutic potential of MSCs. Keywords: GEM; MSCs; adipogenesis; metabolic differences; metabolic reconstruction; osteogenesis.Icelandic Research Fun