| 1. |
- Munthe, Christian, 1962
(författare)
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Pure Selection. The Ethics of Preimplantation Genetic Diagnosis and Choosing Children without Abortion
- 1999
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Preimplantation ge¬netic diagnosis (PGD) is taken to mark the starting-point of a new phase in human reproduction, where the possibility of choosing children on genetic grounds without having to resort to ethi¬cally controversial procedures (such as abortion) will grad¬ually increase. Ethical and political issues actu¬alised by this develop¬ment are addressed. The discussion touches upon issues regarding the moral status of em¬bryos and gametes, the moral import of respecting individual auton¬omy and its implications for the requirement of informed consent in health-care, the connec¬tion between sickness, dis¬ability and the value of life, the moral status of possible future people, and the connection between choosing children and eugenic policies of the past. Practical policy issues are adressed on the basis of this, as well as an empirical case-study of the intro¬duction of PGD in Sweden. The book ends up in a set of recommendations regarding the management of re¬search on, introduction and routine use of procedures for pure se¬lection, both within health care and from the point of view of society as a whole. It is argued that research on such procedures should be allowed and supported by society. However, tight restrictions regarding the clinical introduction of new procedures in this area is highly desirable. A rough model for implementing such re¬strictions is also pre¬sented. It is further asserted that, although reasons of economy and safety should limit the access to pure se¬lection, society should not apply any explicit restrictions based on ideasregarding how different traits affect a person’s quality of life. It is stressed that, in order to to avoid a re¬sur¬rection of eugenic policies of the past, the development in this field un¬der¬lines the need for continued and strengthen public support to the sick, dis¬abled and mentally retarded.
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| 2. |
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| 3. |
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| 4. |
- Wik, Torsten, 1968
(författare)
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An investigation of the fast dynamics in a nitrifying trickling filter
- 1996
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The fast dynamics of a large pilot scale nitrifying trickling filter (NTF) using effluent waste water from Rya Waste Water Treatment Plant in Göteborg, Sweden, has been investigated experimentally and by simulations. The plant is 7.2 m high, have a diameter of 2.7 m, and was filled with a cross-flow media with a specific surface area of 226 m^2/m^3. Continuous ammonium meters connected to the NTF measured influent and effluent ammonium concentrations.Two different phenomena may affect the fast dynamics in this type of biofilm reactors: The mixing in the bulk flow and the dynamics within the biofilm, i.e. the mixing in the biofilm and the response time for the bacteria to changes in substrate concentrations.Pulse response experiments conducted at two different flows (7.3 l/s and 14.5 l/s), where dissolved LiCl was used as trace substance, showed that the flow through the NTF could not be characterized as laminar, but significant mixing occurs inside the plant. The residence time distributions are well approximated by four identical continuously stirred tanks in series, and from the mean residence time the liquid film thickness was estimated to be 0.5 mm.Two experiments, where the influent ammonium concentration was rapidly increased while the flow was held constant at 14 l/s, were also conducted as well as an experiment where the flow was stochastically varied around 12 l/s. Comparisons are made between the measured effluent concentrations in these experiments and simulations of a model of the plant, where the NTF is divided into a series of continuously stirred tank reactors (CSTRs) having the total volume estimated from the pulse response experiments. The nitrification rate in each CSTR is modelled as a first order dynamic system driven by a physically derived expression of the stationary nitrification rate. Simulations for different values of the time constant of this dynamic system, and comparisons with the experimental data, shows that the dynamics within the biofilm are much faster than the dynamics of the mixing in the bulk. Implicitly, this means that the response times for the nitrifying bacteria to changes in ammonium bulk concentration were less than a few minutes. Hence, the fast dynamics in the biofilm can in many cases be neglected, which greatly facilitates simulations of many nitrifying biofilm reactors when more complex biofilm models are used.
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| 5. |
- Wik, Torsten, 1968
(författare)
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Experiment utförda på en nitrifierande biobädd 1995
- 1996
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- A number of experiments was conducted on a pilot scale nitrifying trickling filter during 1995. The experiments aimed for better knowledge of the flow-dependent fast dynamics, and the slow bacterial dynamics.The residence time distribution was investigated by a number of impulse response experiments where dissolved LiCl was added to the influent. The experiments showed that the amount of water in the trickling filter is almost independent of the flow through the plant, and corresponds to a liquid film thickness of approximately 0.5 mm. The residence time distribution can be approximated by a model with four or five identical and ideally continuously stirred tanks.Based on the results of the impulse response experiments the plant is modelled by four continuously stirred tank reactors in series, where the nitrification in each tank is described by a physically derived nonlinear expression.Data from a few step response experiments, where the ammonium concentration in the influent was raised from a low constant level to a high constant level at a constant flow through the plant, was compared to model simulations. The comparisons showed that the fast dynamics in the biofilm can be neglected in comparison to the dynamics caused by the mixing in the bulk and the residence time distribution. Implicitly, this means that the response time for the active nitrifying bacteria to changes in ammonium concentration is less than a few minutes, also when the ammonium load has been very low for a long time.An experiment, where the flow was stochastically varied around an operating point during one day, showed that the simple model derived sufficiently well describe the fast dynamics of nitrifying trickling filter also when the flow changes. When the ammonium concentration in the effluent is low, a model where the nitrification rate is assumed constant is not sufficient.The slow dynamics that depend on the growth and decay of the active nitrifying bacteria was investigated by a three months long step response experiment, where the ammonium concentration in the influent first was held at a high level (not full nitrification) for approximately one month and then at a low level (approximately 50% of the nitrifying capacity) for one month, and finally at the same high level as before for one more month. In spite of several practical problems, the experiment indicated that it takes one to two weeks for the concentration of active bacteria in the biofilm to increase to a new higher concentration after the raise in influent ammonium concentration. The corresponding increase in nitrification rate is approximately 20%.The two periods of the same high influent ammonium concentration was during periods with different water temperature. Comparisons of the nitrification rate between the two periods indicated a stronger dependency on the temperature than has earlier been observed. The standard temperature dependency of the maximum growth rate for nitrifying bacteria that are used for laboratory scale experiments may well apply also for this large scale process.During periods of the experiment the ammonium sensors were not working. Therefore the possibility to determine the influent ammonium concentration based on the flow into the plant was investigated. Both black box models and a physically based model was fitted to data. The investigation showed that with a good model of the influent flow to the plant it may be possible to predict the ammonium concentration with quite good accuracy.The trickling filter was flooded weekly for a couple of hours for predator control. An investigation of the nitrification rate before and after the floodings showed no short term effects of the flooding.When the pilot plant was taken out of operation at the end of the year the uppermost meter of the plant was investigated. It was observed that the biofilm thickness was approximately 0.5mm and no bare surfaces without biofilm could be observed.
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| 6. |
- Wik, Torsten, 1968
(författare)
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Nitrifikation i biobädd - Puls och stegsvarsexperiment utförda på Sjölundaverket i maj 1997
- 1997
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In May 1997 a number of experiments were carried out on a pilot scale nitrifying trickling filter: one pulse response at a low flow, one pulse response at a high flow, a step increase in influent ammonium concentration at the higher flow, and a step increase in flow from the lower flow to the higher one. Samples were taken with short intervals from both the influent and the effluent. The pulse responses show that the mean residence time does not increase inversely proportional to the flow, which can be explained by an increase in the volume of bulk water with flow. Comparisons between data and simulations of model that has been derived to simulate the fast dynamics of nitrifying trickling filter indicate that the flow is not laminar. The step response experiments gave smooth responses in the measured effluent concentrations. The transients were similar for both step experiments. However, the effluent ammonium concentration increased faster in the experiment where the flow was increased. No overshoot in effluent nitrite concentration could be observed, something that could be expected if the increase in nitrite oxidation was slower than the increase in nitrification. Simulations, using the developed model, and data from corresponding experiments carried out on a very similar plant at Ryaverket in Göteborg closely agree. So does the pulse responses from Sjölunda, but the observed step response in effluent ammonium concentration was significantly slower than the model predicts. Further, even though the influent concentration of total dissolved nitrogen remained the same during the experiments the effluent concentration dropped after the step was introduced and reached the initial value again after approximately 30 minutes. This indicates an accumulation of nitrogen in the filter. A possible explanation is adsorption of ammonium on/in the biofilm. This phenomena was not observed in the experiments at Ryaverket. Reasons for this may be found in differences in water quality. The water at Sjölunda is much harder, has a higher alkalinity and a higher pH.
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| 7. |
- Agerberth, B, et al.
(författare)
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FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis.
- 1995
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 92:1, s. 195-9
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Tidskriftsartikel (refereegranskat)abstract
- PR-39, a proline/arginine-rich peptide antibiotic, has been purified from pig intestine and later shown to originate in the bone marrow. Intending to isolate a clone for a human counterpart to PR-39, we synthesized a PCR probe derived from the PR-39 gene. However, when this probe was used to screen a human bone marrow cDNA library, eight clones were obtained with information for another putative human peptide antibiotic, designated FALL-39 after the first four residues. FALL-39 is a 39-residue peptide lacking cysteine and tryptophan. All human peptide antibiotics previously isolated (or predicted) belong to the defensin family and contain three disulfide bridges. The clone for prepro-FALL-39 encodes a cathelin-like precursor protein with 170 amino acid residues. We have postulated a dibasic processing site for the mature FALL-39 and chemically synthesized the putative peptide. In basal medium E, synthetic FALL-39 was highly active against Escherichia coli and Bacillus megaterium. Residues 13-34 in FALL-39 can be predicted to form a perfect amphiphatic helix, and CD spectra showed that medium E induced 30% helix formation in FALL-39. RNA blot analyses disclosed that the gene for FALL-39 is expressed mainly in human bone marrow and testis.
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| 8. |
- Andersson, Mats
(författare)
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Biocatalysed redox reactions in aqueous and organic media
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals mainly with biocatalysed methods for stereoselective reduction. D-(S)-chlorolactic acid was produced by both microbial and electromicrobial reduction of chloropyruvate using whole cells of Proteus vulgaris and an artificial electron mediator. The electron donor was formate, hydrogen gas or the cathode in an electrochemical cell. Since chloropyruvate was susceptible to mediator dependent non-enzymatic dehalogenation the choice of mediator was of importance for the obtainable yield of chlorolactic acid. The best results were obtained using 1,1'-carbamoylmethyl viologen. For large scale (mmol) synthesis, formate and formate dehydrogenase was the best method to regenerate the mediator and it was beneficial to add the chloropyruvic acid continuously during the reaction so as to avoid side reactions. A productivity of 8300 mmol kg-1 h-1 and a space time yield of 68 g l-1 d-1 was obtained. Hydrogenase driven NADH regeneration using permeabilised whole cells of Alcaligenes eutrophus was shown possible and used for lactate dehydrogenase and horse liver alcohol dehydrogenase (HLADH) catalysed reductions in aqueous media. The immobilisation of the cells in alginate and addition of reducing agents as dithiothreitol improved the stability. The permeabilised whole cell approach was also suitable as NADH regenerating catalyst in aqueous organic two-phase media (i.e. ¾10 % water). The permeabilised cells were co-immobilised together with HLADH and NAD by deposition on Celite. Hydrophobic solvents such as heptane and toluene were found to provide high activity. A turnover of the NAD of 200 and a spacetime yield of 10 g l-1 d-1 was obtained in heptane with 10 % water. Furthermore, the stability of HLADH in dry organic solvents could be well correlated to solvent descriptors by PLS (projection to latent structure) analysis of the data. Finally, Celite immobilised chloroperoxidase from Caldariomyces fumago was shown to be able to catalyse the oxidation of bensyl alcohol using tert-butyl hydroperoxide as oxidant in organic media at water activities above 0.6. Highest enzymatic rate was obtained in water saturated cyclohexane. The apparent Km for bensyl alcohol was 13 mM.
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| 9. |
- Andersson, Maria
(författare)
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Protein stabilization. Some methods and mechanisms
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The effect of different additives on protein stability was studied, and the basis for stabilization was investigated at molecular level. The addition of sorbitol enhanced thermal stability of hen egg white lysozyme in aqueous solution. NMR spectroscopy revealed changes in the relaxation properties of Ala and Thr methyl groups in lysozyme, indicating compression of the enzyme as a consequence of preferential exclusion of the polyol from the enzyme surface together with enhanced water structure. Displacement of water from the enzyme surface was also observed, indicating presence of close contacts between sorbitol and lysozyme besides exclusion. The polycation, poly(ethyleneimine) (PEI), increased the shelf life of number of proteins at temperatures above ambient. Porcine muscle lactate dehydrogenase (LDH) retained its activity completely for one month in the presence of PEI at pH 7.2 while in its absence, more than 50% of the activity was lost already after two weeks. Circular dichroism confirmed substantial preservation of secondary structure during the period of storage, however, PEI did not have any effect on the denaturation temperature of LDH. Sorbitol, on the other hand improved the thermodynamic stability of LDH but not the storage stability. Freeze-drying LDH in the presence of PEI also resulted in significantly improved storage stability of the dried preparation. The interactions between PEI and LDH were studied using dynamic light scattering and intrinsic tryptophan fluorescence. Aggregation of LDH was seen to decrease substantially with the polymer present in solution. Formation of a complex between PEI of different molecular weights and LDH was observed, the interactions being rather weak. The stabilizing effect of sorbitol and PEI and also several other additives against protein oxidation was investigated using LDH as a model. Oxidation of the enzyme was performed using CuSO4 and H2O2, either individually or together. PEI was shown to be the best stabilizing agent, followed by EDTA, against both metal ion and hydrogen peroxide mediated oxidation. The protective effect of PEI is attributed to its chelating properties and the close contacts between the polymer and enzyme. The combination of PEI and sorbitol was shown to protect against both oxidation and thermal denaturation. Immobilization of trypsin to a thermo-responsive reversibly soluble-insoluble polymer, poly-N-isopropylacrylamide, was performed and stability of the enzyme conjugate was studied. The immobilization increased the resistance of trypsin towards autolysis. Stability of the enzyme towards heat and organic solvents was improved. The enzyme conjugate could be recycled several times without activity loss.
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| 10. |
- Barros, Raúl J
(författare)
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Influence of Internal Diffusional Limitations on the Performance of an Immobilized Enzyme in Organic Medium
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The influence of mass-transfer limitations on the performance of immobilized a-chymotrypsin operating in acetonitrile medium has been investigated. The enzyme was immobilized by deposition on various porous carrier materials such as celite, polyamides of different particle sizes, controlled-pore glasses, polypropylene or polyacrylamides. When carrying out kinetically controlled peptide synthesis reactions catalyzed by these preparations, mass-transfer effects have been observed. It has been shown that internal diffusional limitations are the mechanism responsible such mass-transfer effects. A correlation between observed activity towards a given reaction at a given enzyme loading and the morphological characteristics of the support material has been developed, taking into account the effects of internal diffusion. The factors that affect substrate diffusion and enzyme kinetics are discussed, because both processes must happen at the same rate in simultaneous reaction and diffusion. The extent of internal diffusional limitations can be controlled by changing enzyme loading, support material, or the intrinsic velocity of the reaction carried out. The intrinsic kinetics of the studied reactions have been studied in the absence of mass-transfer effects by immobilizing the enzyme on nonporous glass beads. Internal diffusional limitations influence the performance of the immobilized enzyme in many ways: Strong diffusional limitations reduce the specific activity of the enzyme preparations. The initial rate per amount of preparation can even decrease with increased enzyme loadings in the case of very low porosity supports, due to reduced available space for substrate diffusion. Internal diffusional limitations can be relaxed by the presence of insoluble hydrochlorinated nucleophile, presumably by promoting the desorption of part of the enzyme from "overloaded" supports. Internal diffusional limitations also decrease the apparent specificity of the chemical transformations. Acyl donor specificity and enantioselectivity in the conversion of a racemic acyl donor are much more affected than nucleophile specificity. The extent of the effect on nucleophile specificity depends on the size of the used nucleophile. Strong internal diffusional limitations still increase the apparent stability, both storage and operational, of the enzyme preparations. A numeric model has been developed to describe the effects of internal diffusional on initial activity and nucleophile specificity. The model accurately describes experimental observations such as plateau-shaped initial rate profiles, the stronger influence on initial rate than on nucleophile specificity and reduction of initial rate with increased enzyme loading with low porosity supports. Besides showing that internal diffusional limitations influence all aspects of enzyme performance, conceptual and numerical explanations to the observed effects have also been provided.
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