For the performance assessment of a deep storage of spent nuclear fuel, the validity of results from laboratory studies often need to be demonstrated by experiments performed under conditions as close as possible to "the real case", preferably in situ. Two kinds of in situ experiment series were carried out: Apart from the experiment cell which is separately designed for each type of experiment, CHEMLAB contains pumps, tracer reservoirs, a number of multi-channel valves and fraction collectors.
For each type of migration experiment, different cells are used. The main objective of LOT is to examine changes in clay properties under deep repository conditions, but several other experiments are contained in LOT, such as copper corrosion and bacteria tests.
Radioactive isotopes were added in one block to examine the diffusion of cations under the conditions LOT offers. KBS-3 Since this work is closely related to the Swedish storage of spent nuclear fuel, I will start with a brief summary of the suggested Swedish model for long term storage of spent fuel.
The principle is to encapsulate the spent fuel in canisters made of stainless steel and copper. The canisters will be emplaced approximately five hundred metres below ground, embedded in compacted bentonite clay. The gallery will be filled with a mixture of sand and bentonite clay.
There are four main barriers for the radioactive elements to pass through before they enter the biosphere, see Figure 1. Figure 1: The four barriers in KBS-3; The fuel, the copper canister, the bentonite clay and the bedrock. Most of the other radionuclides radioactive isotopes in the nuclear waste are incorporated in the UO2-matrix and the rate of dissolution of the UO2-matrix dissertation writing for payment block determine the release of radionuclides.
The stainless steel will serve as mechanical support, while copper is the chemical barrier. Pure copper is a very stable element under the prevailing conditions. A recent review of copper corrosion under deep storage conditions estimates that the life-time of the copper canister exceeds years1. Bentonite clay expands when it takes up water. Since there will be a limited space to expand into, the bentonite will instead become very compact, almost like concrete.
Any transport to or from the canister will thereby occur by diffusion. Bentonite also has good pH buffering capacity and will keep the pH of the storage constant around When radionuclides escape the three first engineered barriers, they will travel by hydraulic flow in fractures in the bedrock and by matrix diffusion through the bedrock.
Many of the radionuclides in the spent fuel are readily sorbed to mineral surfaces and their transport will thereby be strongly retarded. Radionuclides Spent nuclear fuel contains a wide range of radionuclides; activation products originating from neutron capture by metals in the fuel, fission products from the cleaved nuclei and actinides originating from neutron capture by uranium. In a nuclear waste repository there are a number of important parametres to consider when evaluating the relative hazards of the different radionuclides to man.
The quantities, half-lives and mobilities of the radionuclides are very important factors, as well as radiation type, uptake and physiological behaviour in the human body. Table radiology residency personal statement displays in this respect the most important radionuclides in irradiated nuclear fuel.
As can be seen, the fission products best cv writing services qld and Cs, the plutonium isotopes Pu, Pu, Pu and Am all have high specific activities and are therefore of great interest.
Iodine is less abundant but the anion I- is weakly interacting, i. When exploring the diffusion behaviour of sorbing cations, the mechanism by which the cations bind to mineral surfaces is a key feature. The two former are of obvious interest since their specific activities are relatively high in the spent fuel elements.
Strontium and caesium sorb predominantly to mineral surfaces by cation exchange. The strength of the bond to the mineral surface is very much related to the degree of hydration of the ions2.
Cobalt is interesting since it sorbs to mineral surfaces by surface complexation. At high pH, cobalt sorbs more readily to mineral surfaces than at lower pH. Bentonite Clay Bentonite clay is a volcanic ash but DO MY HOMEWORK SERVICES usually treated to obtain desirable properties. American Colloid Co. The montmorillonite sheets are connected to each other by layers of exchangeable cations, see Figure 2.
Iron, copper and potassium appear as exchangeable cations to a small extent. The chemical formula for montmorillonite is Na0. Water molecules are readily adsorbed between the sheets, causing the clay to swell. The main diffusion path through montmorillonite is between the sheets of the clay. The sheets are connected to each other by layers of exchangeable cations.
The intralayer cations thus hold the sheets together by electrostatic forces. When exposed to water, dry montmorillonite adsorbs water in the intralayer region and thereby disjoins the clay particles. The degree of expansion depends on the cations located in the intralayer region. Depending on the expansion between two montmorillonite sheets, two types of swelling mechanisms may be distinguished; crystalline and osmotic swelling.
Crystalline swelling is a result of the hydration of call to action persuasive essay surface. This is called osmotic swelling. The name comes from a repulsive osmotic force due to the interaction of the layers, limited only to some extent by Van der Waals forces. It has been constructed mainly by SKB "with the intention to enable the knowledge of all processes involved in a deep repository to be collated and developed".
The total length of the tunnel is about 3. The CHEMLAB experiments were carried out at two sites, one at a depth of metres and the other at a depth of metres, while the LOT experiments were performed at a depth of metres. Diffusion Diffusion is the mechanism by which components of a mixture are transported around the mixture by means of random molecular Brownian motion. If there is a chemical potential gradient in a system, diffusion will take place to balance the gradient.
The change in chemical potential with distance can be expressed: Balancing the two forces gives for each diffusing element ion, atom or molecule: Bentonite swells on taking up water and since there is a limited volume into which the clay can expand in a deep repository, it will instead become very compact with water filled pores.
In porous media, solutes move by diffusion in the pore water. Da describes the macroscopic diffusion, i. The relationship between De and Da is thus: To explain these observations it has been suggested that diffusion of sorbed species takes place in the Stern layer close to the surface of the clay as well.
Assuming the diffusion of sorbed species to be Fickian, the apparent diffusivity would be: When experimentally determining diffusivities, different techniques are used, and the data must be treated in accordance with the experimental technique. In laboratory diffusion experiments with strongly sorbing cations, the time required to reach steady-state is quite long.
However, service to others essay time dependence of the dissertation abstracts in break-through curve and the concentration profile in the diffusion cell can be analyzed, which reduces the time needed to carry out an experiment.
Numerical methods are then usually used to evaluate the results, see further Section 3. A common experimental set-up for through diffusion experiments is illustrated in Figure 5. C0 CL 0 x L Figure 5: Typical experimental set-up for through diffusion experiment. By integrating with respect to t, we obtain the cumulative amount of diffusant Qt that has passed 11 in time t.
If the initial concentration in the cell is zero and the concentration at the outlet side is kept constant zero then: Introduction Diffusion of ions in bentonite clay has been studied extensively However, there are still processes that are not fully understood. One is the diffusion of cations, which has repeatedly been reported to be faster than predicted from a pore diffusion model based on the assumption of diffusion in the pore water and immobilization hard work pays off essay sorption.
The explanation offered is an additional diffusion process taking place in the layer close to the surface of the bentonite, often referred to as surface or surface related diffusion. To investigate the sorption mechanisms for strontium, caesium and cobalt, batch sorption experiments were carried out at different pH and at different ionic strengths.
Anion diffusion in bentonite clay is another matter that is not fully understood. Often in anion diffusion experiments, only the break-through curve is considered. At steady state, a plot of the accumulated amount diffused through a bentonite barrier versus time becomes a straight line.
However, when the concentration in the cell is plotted versus distance from inlet, the profile obtained is not a straight line, clearly indicating that the diffusive transport through the bentonite is not at steady state. To provide a better insight into anion diffusion, a series of through diffusion experiments were performed at different levels of salinity and compaction of the bentonite.
Experiment Performance To obtain sorption coefficients Kd -values and diffusivities, two different types of experiments were performed; chicago style citation dissertation footnote sorption and through diffusion experiments.
Different simulated groundwaters, NaCl and NaClO4 solutions of different concentrations, were used to vary the ionic strength. The experimental set-up in the through diffusion tests can be seen in Figure 6.
Bentonite clay was compacted to a dry density of 1. The two sides of the bentonite cell were connected to an inlet and an outlet vessel, respectively, via pumps.
The bentonite was saturated with the solution used, after which small volumes of the radionuclide s to be studied were added to the inlet reservoir. While pumping, the concentration at the inlet remains constant within a few percent and the 13 concentration at the outlet is very low.
Small samples were taken at intervals from both vessels to ensure that the concentration remained constant at the inlet side and to obtain the breakthrough curve at the outlet side. At the end of the experiment, the bentonite was sliced into thin sections. These sections were then weighed and analyzed for activity to obtain the concentration profile in the clay. Schematic drawing of the experimental set-up for the through diffusion experiments. Sorption was also measured in batch experiments.
Bentonite was suspended in solutions spiked with the radionuclide to be studied. The system was left to equilibrate, after which samples from the solution were analyzed with respect to activity.
Data Evaluation The cells used in the experiments are equipped with filter plates to avoid expansion of the bentonite clay. Schematic representation of the diffusion cell. The bentonite clay is sandwiched between two filter plates. At the boundary between the inlet filter and the compacted bentonite the following conditions reign: The corresponding transport equation and boundary conditions for the outlet filter are given by: This quantity Q t is given by equation Cations 3.
Results Figure 8a displays a typical concentration profile in a bentonite cell after an experiment. Figure 8b: Cation Concentration Dependence Through diffusion experiments were carried out as described in Section 3.
Data from ionic strength dependence studies by Eriksen and Jacobson12, Muurinen17 and Oscarsson et. As can be seen, there is a strong dependence of the ionic strength on the Kd -values.
This implies that the main sorption mechanism for these two ions is sorption by ion exchange. The dependence is simply due to competition between the ions studied and the ions in the solution.
Surface Related Diffusion Figure 10 displays the dependence of the apparent diffusivity on Kd-values for different cations. Included in the plot are works by Eriksen and Jacobsson12 and Muurinen17 note that the values from Eriksen and Jacobsson12 originate from two different experimental techniques.
With increasing Kd the diffusion is faster than expected for the case of pore water diffusion and complete immobilization of the sorbed species.
The apparent diffusivity in a system encompassing pore water and surface related diffusion is, as described above, given by equation Apparent diffusivities plotted versus Kd. As can be seen, the curves fit well with the experimental data, although one should keep in mind that another variable has been added and the curves should therefore fit better.
Anions 3. Results and Discussion A number of through diffusion experiments on I- and Cl- were carried out as described in Section 3. Again, the data obtained were a break-through curve at the outlet of the experiment cell and an activity profile within the cell. Typical high clay density data are shown as accumulated activity at the outlet of the diffusion cell versus time Figure 11a and specific activity versus distance from inlet of the compacted bentonite Figure 11b.
A typical breakthrough curve of iodide, carrier concentration is M, dry density is 1. To reveal the sensitivity of the curve fitting, three different simulations are displayed. Diffusion of iodide I in bentonite compacted to 1. Since yeast does not contain peptidoglycan, this protein was instead named bovine oligosaccharide-binding protein, bOBP.
A camel PGRP has been isolated from milk and was suggested to function as an antibacterial factor Kappeler et al. Sleep-depravation can also be induced by peptidoglycan fragments Johannsen et al.
A functional role for the rat PGRP as a modulator of peptidoglycan-induced sleep deprivation was suggested Rehman et al. They all have a similar fold as phage T7 lysozyme Cheng et al. They all share a similar peptidoglycan-binding groove with the beta-sheet as a floor and with walls flanked by one of the helices and five of the loop-regions. The enzymatic PGRP-LB has, just like phage T7 lysozyme, a zinc ion bound to one cysteine and two histidine residues in the catalytic centre.
The 35 metal co-factor is not included in the other PGRP structures. Common to all PGRP structures, but not present in T7 lysozyme, is an extra loop-region located on the back of the protein relative to the binding cleft. Adapted from Kim et al. Nature Immunology 4, Figure 9.
This feature speaks against the proposed cytoplasmatic localization of some PGRPs lacking an N-terminal signal-peptide, because the reducing cytosolic environment will most likely disrupt disulphide bonds. PGRP H. PGRP C. PGRP B. PGRP M. Extracellular factor of the Toll pathway, putative receptor.
Function unknown, putative membrane protein. Main receptor of Imd-pathway. Function unknown, membrane bound. Function unknown. Receptor of Imd-pathway and possibly involved in PPO activation. Function unclear, negatively affects Imd-pathway signaling, membrane bound, protein contains two PGRP-domains. Yoshida et al. Expressed in neutrophil granula Liu et al. Expressed in neutrophil granula Cho et al. Expressed in esophagus Liu et al. Mainly expressed in liver.
Present in Wang et al. Table 1. Overview of the functional properties of PGRPs. Drosophila melanogaster Fruit flyB. Bombyx mori Silk mothH. Holotrichia diomphalia Korean Large beetleC. Camelus dromedaries CamelB. Bos Taurus CowR. Rattus norvegicus RatM. Mus musculus MouseH. Homo sapiens Human. In particular, the involvement of peptidoglycan recognition proteins, PGRPs, as immune receptors was the subject of the investigation.
However, the goal was extended during the course of the study to include the characterization of enzymatic PGRPs. At this time, many of the intracellular components of the Toll and Imd pathways were well-characterized but a receptor triggering the pathways had yet not been found.
The Toll receptor itself was clearly not a bacterial receptor in striking contrast to the mammalian Tolllike receptors TLRswhich had been shown to bind a repertoire of different microbial ligands. We imagined that the soluble Drosophila PGRPs could either function as opsonins that bind to bacteria and stimulate phagocytosis, or else that they could function as co-receptors to a membrane receptor, e.
One of our strategies was to assay immune gene induction in the Drosophila S2 cell line after challenge with bacterial products and to assay the expression of antibacterial peptide genes after addition of PGRP to the cell culture medium.
Initial studies by Gang Liu had shown that pretreatment with PGRP-SA had an inhibitory effect on cecropin expression instead of the elevated expression that was expected if the protein had been a receptor the result is fully explainable in light of later findings.
It was surprising that a knock-out of a soluble PGRP displayed such a clear phenotype because the Drosophila genome comprises six very similar 38 short putatively exported PGRP proteins.
This finding was also the starting point of a new track of PGRP research. Enzyme characterization Paper I Insoluble peptidoglycan isolated from bacteria is a complex polymeric macromolecule of undefined size. Using peptidoglycan as an enzyme substrate limits the possibilities to define enzyme kinetic constants that typically require a defined substrate that is converted to a defined product possible to measure.
To obtain a rough estimate of the enzymatic properties of PGRP-SC1B we analyzed the rate by which a turbid solution of peptidoglycan turns clear. The highest activity was recorded against S. A mutational analysis pointed out two additional residues as being required for the amidase activity.
Interesting to note was that none of the receptor PGRPs has all the five residues retained. A critical cysteine residue, being one of the zinc ligands, is replaced by a serine residue in the peptidoglycan binding receptor-PGRPs i. We decided to examine what role this cysteine had for SC1B activity. By mutagenesis I did exchange it with a serine or an alanine residue. As expected, the cysteine was absolutely required for the enzymatic activity but the mutants had not lost their peptidoglycan binding capabilities.
The mass spectrum shows a number of peaks but all correlate to products produced by the action of an N-acetylmuramoyl L-alanine amidase cleavage and it was firmly established that PGRP-SC1B has the same activity as T7 lysozyme.
We experimentally demonstrate dissertation autism it is an enzyme with N-acetylmuramoyl Lalanine amidase activity and that it has a preference for DAP-type peptidoglycan. To examine if PGRP-SC1B is bacteriolytic we extensively assayed antibacterial activity against a range of different bacteria but with negative results.
What could the physiological role of a peptidoglycan degrading enzyme be if it was not antibacterial? As peptidoglycan is a highly immune-stimulatory macromolecule, a possible function could be to modify this property. We speculated that the degradation products could either give a stronger immune response than the intact cell wall because the ligands would more widely spread to cells and tissues, or else that the degradation products papers on nursing be less stimulatory.
To test this we challenged Drosophila cells with the SC1B degradation products and it was clear that the immune induction was much reduced as compared to intact peptidoglycan or lysozyme-degraded peptidoglycan.
This observation led us to suggest a scavenger function for the protein. Peptidoglycan fragments will most likely spread systemically when bacterial lysis is caused by antibacterial peptides or other factors during an infection. A peptidoglycan scavenger function would be beneficial for the host in order to restrict the duration of the immune response and thereby limit the damages caused to own tissues. To bring levels of immune thesis about religion molecules back to zero is likely a prerequisite for the fly to be able to respond to a second infection.
It must be stressed, however, that this is an indicative observation in vitro and a possible PGRP scavenger function still remains to be shown in vivo. However, there is also a weak expression from the fatbody Werner et al.
Possibly, SC1B is exported to good persuasive speeches gut and is taking part in bacterial degradation as a digestive enzyme. This would be in analogy with the six Drosophila lysozymes that are expressed in the gut Daffre et al. However, this is the only bacterial species PGRP-SB1 showed activity against, despite an exhaustive search for antibacterial activity against other bacteria including several Bacillus species.
At present we do not know the feature s of the B. A possible explanation to the PGRP-SB1 bactericidal activity could be that the distribution or composition of teichoic acids being different in B. It was the first bacterial pattern molecule to be linked to a specific receptor TLR4 of the human innate immune system Poltorak et al. Also in studies of the insect immune system, LPS has been extensively used to elicit immune gene expression.
An LPS receptor was therefore expected to be found in control of the Drosophila immunity pathways. Even if peptidoglycan is a constituent of the Gram-negative bacterial cell-wall, it is hidden underneath the LPScontaining outer membrane.
It is not easy to envisage how a receptor would be able to penetrate the lipid-bilayer to get access to the peptidoglycan. However, an alternative explanation could be the presence of peptidoglycan impurities in the LPS preparation.
The purity issue has been central in the study of mammalian Toll41 like receptors and their ligands. The study in Paper IV takes the impurity issue a step further and analyses the LPS preparation after it has been fractionated by gelfiltration. Indeed, the material that induces Drosophila cells from the LPS-solution that had been treated with a peptidoglycan digesting enzyme has a lower molecular weight than un-treated LPS.
They showed instead that the Toll and the Imd-pathway discriminately can be activated by peptidoglycan of Lys-type and DAP-type, respectively. An LPSinjection to the flies gave the same response as an injection of sterile water. However, the response from the sterile control injection was high and could possibly have masked a weak LPS response.
In one of these studies a chromosomal mutation in the non-PGRP domain, thus affecting all three spliceforms, totally blocks the Imd-pathway Gottar et al. A similar phenotype was reported in one of the other studies characterizing a chromosomal mutation affecting the PGRP-LCx domain Choe et al. In a cell culture system, RNAi was directed toward the different spliceforms to knock-down their expression, one at a time.
Different immune elicitors were then added and the effect on immune gene induction was assayed. The results in Paper IV directly show that LCa is required for induction with monomeric peptidoglycan. A more recent paper from our laboratory Gelius et al.
As shown by Stenbak and colleagues Stenbak et al. Taking this into account provides an explanation why similar experimental results were interpreted differently in Paper III and IV.
It was recently suggested that the receptors of the two pathways could discriminate between peptidoglycans having an L-lysine or a meso-DAP residue in the branching position of the tetrapeptide Leulier et al. As no biochemical data were available, we decided to examine the relative binding affinities of the PGRP receptors and to correlate these with the known elicitor specificities of the two pathways.
In future experiments, it would be interesting to examine how well these peptidoglycans activate the Toll pathway. PGRP-LCx shows a remarkable high affinity for all types of peptidoglycan, which stands in contrast to the DAP-type peptidoglycan preference that has been reported for the Imd-pathway activation. A possible explanation of the strong activation seen with DAP-type peptidoglycan could be the anhydro-MurNAc present at the reducing ends of the glycan strands in Gram-negative homework help river pollution peptidoglycan.
This idea is supported by in a recent study Stenbak et al. Another recent study also supports this idea that the conformation of the MurNAc is instrumental for Toll and Imd activation Filipe et al.
These investigators show that the Toll pathway, the columbian exchange essay contrast to the Imd pathway, is positively activated by peptidoglycan fragments in which the MurNAc has an unreduced flexible conformation. In the model, presented in Paper V, we postulate that an Imdactivating PGRP-LCx homodimer will form when one of the dimer partners binds to a peptidoglycan motif that includes an 1,6-anhydro MurNAc residue and the other binds to an adjacent common peptidoglycan motif.
As activation data could be explained by receptor dimerization, an assay was set up that would enable testing if the proteins possibly get affinity for each other in the presence of the proper ligand.
In this assay one of the recombinant proteins contains a histidine-tag and the other protein interaction partner lacks such tag. The two protein forms are incubated in the presence or absence of a 44 ligand and the incubation mixture is passed through a solid-phase histidinebinding matrix.
If the proteins have affinity for each other then they are both trapped in the matrix, otherwise only the tagged form stays bound. In a second step, the proteins that are bound to the matrix are eluted. The two proteins will thus constitute an activating dimer-complex with LCa serving as an adaptor or transducer and not as a receptor. Again, I want to stress that this model of Imdpathway activation is based on experiments in vitro using cell lines and recombinant proteins.
The structure shows that LCa has a distorted binding groove. Binding data presented are in full consonance with, but do not add anything to, the findings we had already published in paper V. Concluding remarks The work in this thesis has been focused on the recognition of bacteria by innate immune receptors which initiate the triggering of the pathways controlling immune gene expression.
Most of the experiments have been performed in vitro using biochemical protein interaction approaches and molecular biology techniques to derive and manipulate cell lines. The main goal has been to elucidate the biological role of members of the PGRP gene family. Many questions have been answered and many new questions have been formulated. It is still an open question how Gram-negative bacteria are being recognized as we showed that LPS is not an inducer of the Imd-pathway.
Alternatively, peptidoglycan monomers which are lost to the environment by growing Gram-negative bacteria could possible offer an explanation to how these bacteria are being recognized. The existence of the dedicated splice variant PGRP-LCa indicates that recognition of peptidoglycan subunits is instrumental for bacterial recognition.
However, these dimerization events remain to be shown also in vivo. One can, however, foresee that they play important roles by modulating the property of the major stimulant of the Drosophila immune system, namely peptidoglycan.
Aotf dissertation research grant program appreciate the warm and open atmosphere in your lab, the free hands you gave me, and the immense support I had whenever I needed it.
Your generosity in sharing your knowledge and humor has been invaluable. My comrades at the translation lab: Ernesto, Victor, Qing how could you possibly write your thesis that fast? Peter H for one or two games of chess, badminton and billiard, Oliver take care of Jenny and Leon in Copenhagen, Martin for your anti-optimism, Magnus, Magda and Josefin our parties have been missing you, Ann for all the rules and for all the cakes, Robert S, for exiting sub-cloning discussions.
The staff at the rest of our department, the Geneticists and Toxicologists, especially the athletes attending the Innebandy fights. Reseach collaborators: My sister Gunlis, and family, Olle, Fred and Annika for extensive hospitality and support during one of the toughest periods of my life. My brother Roger, and family, Anna-Karin, Emmie and Lise for care, and for introducing me to ornithology, which was the main reason I started this education in the first place -how did I end up with this fly research?
I still cannot give a proper answer…. Den nya dagen gryr. Immunol Rev Agaisse, H. Dev Cell 5, Alexopoulou, L. Nature Atrih, A.
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