| 1. |
- Andersson, Anders G., et al.
(författare)
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Simulation of free surface flow in a spillway with the rigid lid and volume of fluid methods and validation in a scale model
- 2010
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Ingår i: Proceedings, Fifth European Conference on Computational Fluid Dynamics. - 9789899677814
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Konferensbidrag (refereegranskat)abstract
- Simulations on the spilling from a dam were performed and compared to experimental results from a physical scale model. Both mechanical and acoustic methods to measure the velocity were used. The model has three gates leading into the spillway that can be maneuvered separately. At first two of the gates were closed and the inlet flow was high enough to get a fully wetted outlet at the third gate. This case was simulated with a rigid lid approximation since the water surface was considered to be plane. The water surface level was taken from the scale model. In the second case, all three gates were open resulting in a free water surface through all the gates to the spillway. This case was simulated with the Volume of Fluids method were both water and air phase were considered. Water levels, velocities and the shape of the water surface were compared between simulations and experiments. The simulations capture both qualitative features such as a vortex near the outlet and show good quantitative agreement with the experiments.
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| 2. |
- Bergström, Ulf, et al.
(författare)
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Long-term effects of no-take zones in Swedish waters
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Marine protected areas (MPAs) are increasingly established worldwide to protect and restore degraded ecosystems. However, the level of protection varies among MPAs and has been found to affect the outcome of the closure. In no-take zones (NTZs), no fishing or extraction of marine organisms is allowed. The EU Commission recently committed to protect 30% of European waters by 2030 through the updated Biodiversity Strategy. Importantly, one third of these 30% should be of strict protection. Exactly what is meant by strict protection is not entirely clear, but fishing would likely have to be fully or largely prohibited in these areas. This new target for strictly protected areas highlights the need to evaluate the ecological effects of NTZs, particularly in regions like northern Europe where such evaluations are scarce. The Swedish NTZs made up approximately two thirds of the total areal extent of NTZs in Europe a decade ago. Given that these areas have been closed for at least 10 years and can provide insights into long-term effects of NTZs on fish and ecosystems, they are of broad interest in light of the new 10% strict protection by 2030 commitment by EU member states.In total, eight NTZs in Swedish coastal and offshore waters were evaluated in the current report, with respect to primarily the responses of focal species for the conservation measure, but in some of the areas also ecosystem responses. Five of the NTZs were established in 2009-2011, as part of a government commission, while the other three had been established earlier. The results of the evaluations are presented in a synthesis and also in separate, more detailed chapters for each of the eight NTZs. Overall, the results suggest that NTZs can increase abundances and biomasses of fish and decapod crustaceans, given that the closed areas are strategically placed and of an appropriate size in relation to the life cycle of the focal species. A meta-regression of the effects on focal species of the NTZs showed that CPUE was on average 2.6 times higher after three years of protection, and 3.8 times higher than in the fished reference areas after six years of protection. The proportion of old and large individuals increased in most NTZs, and thereby also the reproductive potential of populations. The increase in abundance of large predatory fish also likely contributed to restoring ecosystem functions, such as top-down control. These effects appeared after a 5-year period and in many cases remained and continued to increase in the longer term (>10 years). In the two areas where cod was the focal species of the NTZs, positive responses were weak, likely as an effect of long-term past, and in the Kattegat still present, recruitment overfishing. In the Baltic Sea, predation by grey seal and cormorant was in some cases so high that it likely counteracted the positive effects of removing fisheries and led to stock declines in the NTZs. In most cases, the introduction of the NTZs has likely decreased the total fishing effort rather than displacing it to adjacent areas. In the Kattegat NTZ, however, the purpose was explicitly to displace an unselective coastal mixed bottom-trawl fishery targeting Norway lobster and flatfish to areas where the bycatches of mature cod were smaller. In two areas that were reopened to fishing after 5 years, the positive effects of the NTZs on fish stocks eroded quickly to pre-closure levels despite that the areas remained closed during the spawning period, highlighting that permanent closures may be necessary to maintain positive effects.We conclude from the Swedish case studies that NTZs may well function as a complement to other fisheries management measures, such as catch, effort and gear regulations. The experiences from the current evaluation show that NTZs can be an important tool for fisheries management especially for local coastal fish populations and areas with mixed fisheries, as well as in cases where there is a need to counteract adverse ecosystem effects of fishing. NTZs are also needed as reference for marine environmental management, and for understanding the effects of fishing on fish populations and other ecosystem components in relation to other pressures. MPAs where the protection of both fish and their habitats is combined may be an important instrument for ecosystembased management, where the recovery of large predatory fish may lead to a restoration of important ecosystem functions and contribute to improving decayed habitats.With the new Biodiversity Strategy, EUs level of ambition for marine conservation increases significantly, with the goal of 30% of coastal and marine waters protected by 2030, and, importantly, one third of these areas being strictly protected. From a conservation perspective, rare, sensitive and/or charismatic species or habitats are often in focus when designating MPAs, and displacement of fisheries is then considered an unwanted side effect. However, if the establishment of strictly protected areas also aims to rebuild fish stocks, these MPAs should be placed in heavily fished areas and designed to protect depleted populations by accounting for their home ranges to generate positive outcomes. Thus, extensive displacement of fisheries is required to reach benefits for depleted populations, and need to be accounted for e.g. by specific regulations outside the strictly protected areas. These new extensive EU goals for MPA establishment pose a challenge for management, but at the same time offer an opportunity to bridge the current gap between conservation and fisheries management.
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| 3. |
- Lind, Hans, 1950-, et al.
(författare)
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Bostadsmarknad och ekonomisk tillväxt
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Snabbväxande regioner riskerar att hämmas i sin utveckling på grund av en bostadsmarknad som fungerar dåligt. I samhällsdebatten framhålls ofta att problemen står att finna i ett för lågt bostadsbyggande. I den här rapporten framtonar ett något annorlunda och mycket intressant perspektiv. Författarnas slutsats är att bostadsbristen inte enbart går att bygga bort. Istället är det ett ökat utbud av bostäder i det befintliga beståndet som är den stora utmaningen.
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| 4. |
- Lundström, Yasmin, et al.
(författare)
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Detection of Changes in Immunohistochemical Stains Caused by Postmortem Delay and Fixation Time
- 2019
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Ingår i: Applied immunohistochemistry & molecular morphology (Print). - 1541-2016 .- 1533-4058. ; 27:3, s. 238-245
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we have systematically assessed the influence of postmortem delay (PMD) and fixation time (FT) on the immunohistochemical (IHC) staining outcome. The IHC method is frequently applied on surgical and postmortem samples in diagnostics and research. To replicate the routine situation, brain tissues from pigs were exposed to either storage in a refrigerator (+8°C), that is, PMD (1 to 168 h), or fixed in 10% buffered formalin, that is, FT (18 to 94 d). Subsequently, the tissue was routinely processed into paraffin blocks to enable construction of tissue microarrays (TMA). Sections cut from the TMA blocks were stained applying 13 different antibodies directed against neuronal and glial antigens. Immunoreactivity applying 5 antibodies was influenced by prolonged PMD and applying 2 antibodies by prolonged FT. None of the staining outcomes related to the PMD or FT were predictable. Loss of TMA cores during processing was primarily influenced by pretreatment and by tissue characteristics (gray/white matter). The test model described here confirmed that these 2 variables, PMD and FT, indeed influence the IHC outcome. The PMD and FT are particularly of importance while assessing tissue samples obtained at autopsy. The result above is also of importance while comparing the IHC outcomes seen in the postmortem setting (various PMD/FT) with surgical samples or with IHC outcome seen in experimental animal setting (controlled PMD/FT). Thus, we suggest that the test model described here is considered when assessing the reliability of the IHC outcome when analyzing tissues with various characteristics.
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| 5. |
- Ahlner, Alexandra, 1984-, et al.
(författare)
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Conformational Dynamics and Multimerization of Active Forms of the EphrinB Receptor 2 Kinase Domain
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Active and autoinhibited forms of the ephrinB receptor 2 (EphB2) kinase domain have been studied using NMR spectroscopy. The project was initiated because of the finding that the crystal structures of active forms of the kinase domain and previous NMR studies suggested that a change in inter-lobe flexibility and the sampling of catalytically competent excited states conformations are responsible for activity. Using Carr-Purcell-Meiboom-Gill relaxation dispersion experiments, we have measured millisecond dynamics to identify such states. We have also performed concentration dependent relaxation experiments and analytical ultracentrifugation experiments that report on the effective protein size to look for possible differences in self-association for active and autoinhibited forms of the EphB2 kinase domain. We show that the active but not autoinhibited forms exchange between a ground state and an excited state at a rate of 1900 s-1. Similar results were found for the S677/680A mutant of the protein. The nature and importance of the excited state is still unknown. Our most important finding is that active forms of the kinase domain self-associate in a concentration dependent manner and form tetramers and possibly larger oligomers. Multimerization of the kinase domain may enable the assembly of complexes of downstream proteins and could be important for Eph signaling.
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| 6. |
- Ahlner, Alexandra, 1984-, et al.
(författare)
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Fractional enrichment of proteins using [2-13C]-glycerol as the carbon source facilitates measurement of excited state 13Cα chemical shifts with improved sensitivity
- 2015
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Ingår i: Journal of Biomolecular NMR. - : Springer Netherlands. - 0925-2738 .- 1573-5001. ; 62:3, s. 341-351
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Tidskriftsartikel (refereegranskat)abstract
- A selective isotope labeling scheme based on the utilization of [2-13C]-glycerol as the carbon source during protein overexpression has been evaluated for the measurement of excited state 13Cα chemical shifts using Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion (RD) experiments. As expected, the fractional incorporation of label at the Cα positions is increased two-fold relative to labeling schemes based on [2-13C]-glucose, effectively doubling the sensitivity of NMR experiments. Applications to a binding reaction involving an SH3 domain from the protein Abp1p and a peptide from the protein Ark1p establish that accurate excited state 13Cα chemical shifts can be obtained from RD experiments, with errors on the order of 0.06 ppm for exchange rates ranging from 100 to 1000 s−1, despite the small fraction of 13Cα–13Cβ spin-pairs that are present for many residue types. The labeling approach described here should thus be attractive for studies of exchanging systems using 13Cα spin probes.
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| 7. |
- Ahlner, Alexandra, 1984-
(författare)
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Improved Methods for Characterization of Protein Dynamics by NMR spectroscopy and Studies of the EphB2 Kinase Domain
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteins are essential for all known forms of life and in many lethal diseases protein failure is the cause of the disease. To understand proteins and the processes they are involved in, it is valuable to know their structures as well as their dynamics and interactions. The structures may not be directly inspected because proteins are too small to be visible in a light microscope, which is why indirect methods such as nuclear magnetic resonance (NMR) spectroscopy have to be utilized. This method provides atomic information about the protein and, in contrast to other methods with similar resolution, the measurements are performed in solution resulting in more physiological conditions, enabling analysis of dynamics. Important dynamical processes are the ones on the millisecond timeframe, which may contribute to interactions of proteins and their catalysis of chemical reactions, both of significant value for the function of the proteins.To better understand proteins, not only do we need to study them, but also develop the methods we are using. This thesis presents four papers about improved NMR techniques as well as a fifth where the kinase domain of ephrinB receptor 2 (EphB2) has been studied regarding the importance of millisecond dynamics and interactions for the activation process. The first paper presents the software COMPASS, which combines statistics and the calculation power of a computer with the flexibility and experience of the user to facilitate and speed up the process of assigning NMR signals to the atoms in the protein. The computer program PINT has been developed for easier and faster evaluation of NMR experiments, such as those that evaluate protein dynamics. It is especially helpful for NMR signals that are difficult to distinguish, so called overlapped peaks, and the soft- ware also converts the detected signals to the indirectly measured physical quantities, such as relaxation rate constants, principal for dynamics. Next are two new versions of the Carr-Purcell-Maiboom-Gill (CPMG) dispersion pulse sequences, designed to measure millisecond dynamics in a way so that the signals are more separated than in standard experiments, to reduce problems with overlaps. To speed up the collection time of the data set, a subset is collected and the entire data set is then reconstructed, by multi-dimensional decomposition co-processing. Described in the thesis is also a way to produce suitably labeled proteins, to detect millisecond dynamics at Cα positions in proteins, using the CPMG dispersion relaxation experiment at lower protein concentrations. Lastly, the kinase domain of EphB2 is shown to be more dynamic on the millisecond time scale as well as more prone to interact with itself in the active form than in the inactive one. This is important for the receptor function of the protein, when and how it mediates signals.To conclude, this work has extended the possibilities to study protein dynamics by NMR spectroscopy and contributed to increased understanding of the activation process of EphB2 and its signaling mechanism.
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| 8. |
- Ahlner, Alexandra, 1984-, et al.
(författare)
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Measurement of Protein Backbone 13CO and 15N Relaxation Dispersion at High Resolution
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Three-dimensional pulse sequences for the measurement of Carr-Purcell-Meiboom-Gill relaxation dispersions and new methods for co-processing non-uniformly sampled data are presented. The new methodology was validated for the disordered protein IgA and for an SH3 domain from Abp1p in exchange between its free form and bound to a peptide from the protein Ark1p. We show that the results are similar to ones obtained using traditional experiments and that accurate excited state chemical shifts can be determined. Furthermore, we show that jackknife analysis of down sampled spectra yields robust estimates of peak intensities errors, eliminating the need for recording duplicate data points. The methodology should be useful for characterization of millisecond dynamics in small to medium-sized proteins with poorly dispersed spectra.
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| 9. |
- Ahlner, Alexandra, et al.
(författare)
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PINT: a software for integration of peak volumes and extraction of relaxation rates
- 2013
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Ingår i: Journal of Biomolecular NMR. - : Springer Verlag (Germany). - 0925-2738 .- 1573-5001. ; 56:3, s. 191-202
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Tidskriftsartikel (refereegranskat)abstract
- We present the software Peak INTegration (PINT), designed to perform integration of peaks in NMR spectra. The program is very simple to run, yet powerful enough to handle complicated spectra. Peaks are integrated by fitting predefined line shapes to experimental data and the fitting can be customized to deal with, for instance, heavily overlapped peaks. The results can be inspected visually, which facilitates systematic optimization of the line shape fitting. Finally, integrated peak volumes can be used to extract parameters such as relaxation rates and information about low populated states. The utility of PINT is demonstrated by applications to the 59 residue SH3 domain of the yeast protein Abp1p and the 289 residue kinase domain of murine EphB2.
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| 10. |
- Akke, Mikael, et al.
(författare)
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Protein conformational dynamics by relaxation dispersion
- 2013
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Ingår i: Encyclopedia of biophysics. - Berlin : Elsevier. - 9783642167126 ; , s. 1967-1979
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Protein dynamics is intimately connected to function. Many biochemical reactions are mediated by protein conformational transitions to high-energy states that are often populated at low levels undetectable by traditional methods in structural biology. Nuclear magnetic resonance ( NMR) relaxation dispersion methods ( Relaxation Dispersion) provide a unique means of characterizing this type of protein motion with rate constants ranging from approximately 1–105 s–1 and populations down to approximately 1%. Relaxation dispersion experiments yield a wealth of information about the exchanging system, including the kinetic rate constants, the relative populations of the exchanging states, and the chemical shift differences between these, which depend on the molecular structure. Temperature-dependent experiments enable mapping of the energy landscape in terms of the free energy barrier and the free energy difference between the exchanging states, broken down into enthalpy and entropy. Applications have addressed protein folding-unfolding ( Protein Folding), enzyme catalysis ( Protein Dynamics in Catalysis – Computational Studies), and ligand binding ( Protein–Ligand Dynamics) (Korzhnev and Kay 2008; Baldwin and Kay 2009). This chapter outlines the fundamental principles of relaxation dispersion experiments and their application to protein dynamics. The focus is on heteronuclear experiments performed on isotope-labeled proteins ( Protein NMR – Introduction), where the dynamics is typically probed by 15N or 13C spin relaxation, but experiments have also been developed for 1H.
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