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- Bjørnerud, Atle, 1962-
(författare)
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Proton Relaxation Properties of a Particulate Iron Oxide MR Contrast Agent in Different Tissue Systems : Implications for Imaging
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge of the relationship between in vivo contrast agent concentration and magnetic resonance (MR) signal response is an important requirement in contrast enhanced MR imaging in general and in MR based perfusion imaging in particular. This relationship is a complex function of the properties of the contrast agent as well as the structure of the target tissue. The aim of the present work was to quantify the effects of the iron oxide nanoparticle based intravascular contrast agent, NC100150 Injection, on proton relaxation rates in different tissue systems in vivo in a pig model and ex vivo in phantoms containing whole blood. Methods that enabled accurate relaxation rate measurements in these organs were developed, and validated. From these measurements, trans-compartmental water exchange rates and blood volume could be estimated and the MR signal response could be predicted as a function of contrast agent concentration under relevant imaging conditions. Using a 1.5 Tesla clinical MR system, the longitudinal (R1=1/T1) proton relaxation rates in blood, renal cortex, paraspinal muscle and myocardium were measured in vivo as a function of plasma concentration (Cp) of NC100150 Injection. The transverse (R2* = 1/T2*) relaxation rates were measured in vivo in blood, renal cortex and muscle as a function of Cp and ex vivo in blood as a function of Cp and blood oxygenation tension. The proton nuclear MR (NMR) linewidth and lineshape were analysed as a function of Cp and blood oxygen tension ex vivo at 7.05 T. In muscle and renal cortex, there was a linear correlation between R2* and Cp whereas R2* increased as a quadratic function of Cp in blood. The NMR linewidth increased linearly with Cp in fully oxygenated blood whereas in deoxygenated blood the linewidth initially decreased with increasing Cp, reaching a minimum and then increasing again with further increase in Cp. R1 increased linearly with Cp in blood and from the slope of R1 vs. Cp the T1-relaxivity (r1) of NC100150 Injection in blood at 1.5 T was estimated to be (mean ± SD) 13.9 ± 0.9 s-1mM-1. In tissue, the maximum increase in R1 was limited by the rate of water exchange between the intravascular and interstitial tissue compartments. Using a two-compartment exchange-limited relaxation model, the permeability surface area (PS) product was estimated to be 61.9 ± 2.9 mL/min/g in renal cortex and 10.1 ± 1.5 mL/min/g in muscle and the total myocardial water exchange rate, kt, was 13.5 ± 6.4 s-1. The estimated blood volumes obtained from the same model were 19.1 ± 1.4 mL/100 g, 2.4 ± 1.4 mL/100 g and 11.2 ± 2.1 mL/100 g, respectively in renal cortex, muscle and myocardium.Current T2* based first-pass MR perfusion methods assume a linear correlation between R2* and Cp both in blood and tissue and our results therefore suggest that quantitative perfusion values can not easily be obtained with existing tracer kinetic models. The correlation between MR signal response and Cp is further complicated in the kidney by a significant first-pass increase in R1 which may lead to an underestimation of Cp. In T1-based perfusion methods, low concentrations of NC100150 Injection must be used in order to maintain a linear dose-response relationship between R1 and Cp. The effect of blood oxygenation on the NMR linewidth in the presence of NC100150 Injection enabled accurate estimation of magnetic susceptibility of deoxyhemoglobin and the effect can potentially be used to determine blood oxygenation status.In conclusion, NC100150 Injection is well suited as a T2* perfusion agent due to the large magnetisation and intravascular biodistribution of this agent. T1-based perfusion imaging with this agent is limited by water exchange effects and large T2* effects at higher contrast agent concentrations. Quantitative perfusion assessment is unlikely to be feasible with any of these approaches due to the non-linear dose response.
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| 2. |
- Cheung, Ocean, 1986-
(författare)
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Narrow-pore zeolites and zeolite-like adsorbents for CO2 separation
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A range of porous solid adsorbents were synthesised and their ability to separate and capture carbon dioxide (CO2) from gas mixtures was examined. CO2 separation from flue gas – a type of exhaust gas from fossil fuel combustion that consists of CO2 mixed with mainly nitrogen and biogas (consists of CO2 mixed with mainly methane) were explicitly considered. The selected adsorbents were chosen partly due to their narrow pore sizes. Narrow pores can differentiate gas molecules of different sizes via a kinetic separation mechanism: a large gas molecule should find it more difficult to enter a narrow pore. CO2 has the smallest kinetic diameter in zeolites when compared with the other two gases in this study. Narrow pore adsorbents can therefore, show enhanced kinetic selectivity to adsorb CO2 from a gas mixture.The adsorbents tested in this study included mixed cation zeolite A, zeolite ZK-4, a range of aluminophosphates and silicoaluminophosphates, as well as two types of titanium silicates (ETS-4, CTS-1). These adsorbents were compared with one another from different aspects such as CO2 capacity, CO2 selectivity, cyclic performance, working capacity, cost of synthesis, etc. Each of the tested adsorbents has its advantages and disadvantages. Serval phosphates were identified as potentially good CO2 adsorbents, but the high cost of their synthesis must be addressed in order to develop these adsorbents for applications.
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| 3. |
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| 4. |
- Silverstein, Rebecka A.
(författare)
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Histone deacetylases and their co-regulators in schizosaccharomyces pombe
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The DNA in every eukaryotic cell is wrapped around eight core histones to form the nucleosome. Therefore all events that involve DNA must also involve chromatin and nucleosomes. By regulating chromatin structure the cell can regulate the reactivity of the DNA. One of the most common ways of altering nucleosomes is the acetylation of lysine residues. Two enzymes are required to maintain the correct equilibrium for optimal cell growth: histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs). In general, histone hypoacetylation is correlated with transcriptional inactivation, while hyperacetylation is correlated with active gene transcription. In Schizosaccharomyces pombe, mating type loci are silenced. Deletion of HDAC Hos2 had previously been shown to slightly increase silencing at the mating type locus. To assess whether any other HDAC was necessary for mating type silencing, cells were treated with HDAC poison Trichostatin A (TSA). TSA was found to cause a mild derepression of the mating type locus, indicating that another HDAC was responsible for silencing in this region. The RNA interference nuclease Dcr1 was later identified, and showed to degrade double stranded RNA into small nucleotide fragments. Deletion of dcr1 caused chromosome segregation defects and derepression of centromeric silencing. Rpd3 in S. cerevisiae is recruited to genomic targets by interacting with co-regulator Sin3. S. pombe has three Sin3 homologs. Pst1 interacts with the HDAC Clr6, and like Clr6 is an essential gene, mutants of which display chromosome mis-segregation and derepression of centromeric silencing. Pst1 was required for centromeric cohesion, and localized to centromeres in late S phase. Thus a co-repressor paradigm could be applied to centromere silencing as well. A comparative characterization of HDACs in S. pombe showed that the HDACs had different localizations and histone specificities. The comparison of HDACs was taken further with a genome wide expression analysis and histone density study of mutants. Results indicated that Clr6 was most often involved in promoter initiated gene repression, whereas Hos2 promoted the high expression of growth related genes by deacetylating H4K16ac in their coding regions. A class II HDAC, Clr3, was found to act cooperatively with Sir2 throughout the genome. Using a genomic approach to analyze Pst3, it was established that Clr6 and Pst3 could cooperate to negatively regulate genes by binding to their promoter regions. On the other hand, Pst3 was also involved in the up-regulation of ribosome biosynthesis genes, and could bind to the rDNA.
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| 5. |
- Wright, Sandra A. I.
(författare)
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The genetics of antibiotic production and the role of antibiotics in biological control of Erwinia amylovora by Erwinia herbicola
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Erwinia herbicola is an epiphyte of apple and pear with potential as a biocontrol agent of Erwinia amylovora, which causes fire blight. This research aimed to assess the relative role of antibiotics produced by E. herbicola, Eh318 as a mechanistic basis for biocontrol. A genomic library of Eh318 DNA was constructed in Escherichia coli and two distinct cosmids, pCPP702 and pCPP704, were identified that conferred upon E. coli the ability to produce two antibiotics inhibitory to E. amylovora. The antibiotics were distinct based on their spectra of activity, differential susceptibility to the presence of histidine and arginine and antibiotic production by marker-exchange mutants of Eh318. Transposon mutagenesis and subcloning were used to delineate the Eh318 DNA that enabled E. coli to produce the two antibiotics. The smallest clone that conferred antibacterial activity was pCPP717. Its antibiotic was named pantocin A. The Eh318 insert DNA of pCPP717 revealed three predicted genes, paaA, paaB and paaC, in a 2.7 kb region. The predicted paaA gene product is similar in sequence to a group of biosynthetic enzymes that possess a dinucleotide binding motif. PaaC was judged to encode a membrane protein. The second antibiotic was named pantocin B. Its synthesis is conferred on E. coli by DNA harbored in clone pCPP719. Between 19 kb and 20 kb of Eh318 DNA is needed for the production of pantocin B. Direct Tn5- and marker-exchange mutants of Eh318, deficient in pantocin A and/or pantocin B, were created. The mutant strains were tested for biocontrol ability in immature pear fruit in the laboratory and in apple blossoms in a controlled environment chamber. Results from both assays revealed that the marker-exchange mutant deficient in both antibiotics (Eh440) protected against fire blight less well than Eh318. The single marker-exchange mutants, Eh421 (deficient in pantocin A) and Eh439 (deficient in pantocin B), were not significantly impaired in biocontrol ability, whereas three directly induced Tn5-mutants, Eh454, Eh464 and Eh468, were less effective than Eh318. Thus, pantocins contribute to but are not solely responsible for the biological control of fire blight by E. herbicola Eh318.
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