| 1. |
- Hill, Tobias, et al.
(författare)
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SPRIT : Identifying horizontal gene transfer in rooted phylogenetic trees
- 2010
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 10:1, s. 42-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phylogenetic trees based on sequences from a set of taxa can be incongruent due to horizontal gene transfer (HGT). By identifying the HGT events, we can reconcile the gene trees and derive a taxon tree that adequately represents the species' evolutionary history. One HGT can be represented by a rooted Subtree Prune and Regraft (RSPR) operation and the number of RSPRs separating two trees corresponds to the minimum number of HGT events. Identifying the minimum number of RSPRs separating two trees is NP-hard, but the problem can be reduced to fixed parameter tractable. A number of heuristic and two exact approaches to identifying the minimum number of RSPRs have been proposed. This is the first implementation delivering an exact solution as well as the intermediate trees connecting the input trees. RESULTS: We present the SPR Identification Tool (SPRIT), a novel algorithm that solves the fixed parameter tractable minimum RSPR problem and its GPL licensed Java implementation. The algorithm can be used in two ways, exhaustive search that guarantees the minimum RSPR distance and a heuristic approach that guarantees finding a solution, but not necessarily the minimum one. We benchmarked SPRIT against other software in two different settings, small to medium sized trees i.e. five to one hundred taxa and large trees i.e. thousands of taxa. In the small to medium tree size setting with random artificial incongruence, SPRIT's heuristic mode outperforms the other software by always delivering a solution with a low overestimation of the RSPR distance. In the large tree setting SPRIT compares well to the alternatives when benchmarked on finding a minimum solution within a reasonable time. SPRIT presents both the minimum RSPR distance and the intermediate trees. CONCLUSIONS: When used in exhaustive search mode, SPRIT identifies the minimum number of RSPRs needed to reconcile two incongruent rooted trees. SPRIT also performs quick approximations of the minimum RSPR distance, which are comparable to, and often better than, purely heuristic solutions. Put together, SPRIT is an excellent tool for identification of HGT events and pinpointing which taxa have been involved in HGT.
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| 2. |
- Malm, Richard, et al.
(författare)
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Cracking in the concrete foundation for hydropower generators : Analyses of non-linear drying diffusion, thermal effects and mechanical loads
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- An extensive program for improvement of the hydropower plants in Sweden is currently on-going. The aims are to secure future production and to maintain and further develop an already high dam safety.During inspection, cracks were discovered in the concrete foundation, near the stator and rotor spider supports, at some hydropower stations in Sweden. The cracks were believed to be related to the function of the stator supports and to new patterns of generator operation. In earlier times, the generators ran continuously, while nowadays there are many stops and starts, sometimes even several times during one day. The objective of this study is to understand the complex interaction between the power generating system (stator, rotor, turbine, etc.) and the supporting concrete structure. It is important from a dam safety perspective to determine the causes of the structural cracks that have been found in-situ.A three dimensional non-linear finite element model has been developed in order to analyse formation and propagation of the cracks. Several different load effects have been studied in this project in addition to the mechanical loads during operation. The new pattern of generator operation with several starts and stops lead for instance to variations in temperature which have been studied. Besides this, the uneven drying shrinkage of concrete has also been studied in this project. Thereby, the structural behaviour of a concrete foundation for the power generating system has been analysed taking into account the transient thermal and moisture gradients in combination with dead loads and some of the operational loads imposed to the foundation.The analyses shows that reinforced concrete structure that constitute a support to the generator is subjected to cracking due to the loads considered in this study, where the cracks near the supports are caused by a combination of mechanical loads, long-term drying shrinkage and temperature variations. The analyses showed that even after 20 years, the moisture content in the centre of the thicker part in the concrete foundation still had a high relative humidity. At the same time the concrete close to the free surfaces and the slender parts of the concrete foundation had reached the same relative humidity as the environment. Thereby, a large difference in drying shrinkage is obtained between different parts of the concrete foundation and thereby large forces due to restrain. The analyses showed that the drying shrinkage induced cracking inside the concrete foundation and especially close to the supports of the stator and the rotor spider which coincides with location of the cracks found in-situ.The results show that the cracks found in-situ can be simulated and explained with advanced numerical methods. The results also indicate that the dynamic effect from the loads caused by the power generating system have to be studied further, since a reduced structural stiffness due to cracking may result in larger loads imposed on the structure from the magnetic eccentricity and turbine imperfections or alternatively lead to a fatigue failure of for instance the reinforcement.
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| 3. |
- Marcus, Lars, 1962-, et al.
(författare)
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Developing the spatial capital at the Stockholm Central Station
- 2012
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Ingår i: The Future of Cities and Regions. - : Springer Science+Business Media B.V.. - 9789400725188 ; , s. 297-322
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Bokkapitel (refereegranskat)abstract
- This project concerns the most centrally located and spatially complex area in central Stockholm. It is located directly to the west of the internationally well-known Stockholm City area developed in the 1950s and 1960s. Presently significant reconstruction of the central station and its track areas is under way which will also open up a large new development area in one of the most attractive locations in Stockholm. For this project Spacescape, an architectural office specializing in analysis of urban space and urban development projects in relation to urban life qualities such as, attractiveness, public safety and retail support formed an integrated consultancy group together with architects and landscape architects, delivering evaluation and design support to the project. This concerned both an analysis of the current status of the area, including the spatially complex interior of the central station, as well as support and evaluation of the different stages in the proposal. The themes analysed included spatial capital (accessibility to the rest of the city, especially for people working and living in the city), pedestrian flows, wayfinding, recreational qualities and public safety. Through continuous analyses during the design process Spacescape were able to support the project in a direction providing greater benefits in these areas and telling images show how the new proposal could create a much better outcome than the current one.
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| 4. |
- Nordström, Tobias
(författare)
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Predicting prostate cancer : on the use of biomarkers in prostate cancer diagnostics
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims: The aims of this thesis work were to answer the following questions. Paper I: How prevalent is testing and retesting with prostate-specific antigen (PSA)?; Paper II: Is a genetic score based on single-nucleotide polymorphisms (SNPs) informative regarding the risk of prostate cancer (PCa) in men with low PSA?; Paper III: Are the commercially available tests Prostate Health Index (PHI) and the four-kallikrein panel comparable in aiding biopsy decisions?; Paper IV: Do commonly used medications affect PSA and the risk of PCa? Methods: In Paper I and Paper IV, the population-based PSA cohort STHLM0 was used together with registry-based data. Paper I described limited-duration point prevalence of testing and survival analysis describing retesting with PSA. Paper IV determined differences in PCa risk and PSA level among men using aspirin, statin, metformin or no medication. Paper II included 172 men with PSA at 1‒3ng/ml. Participants were invited according to their genetic score and underwent prostate biopsy. Risk of prostate cancer was assessed using logistic regression. Paper III included 531 men who had undergone a first prostate biopsy. Predictive models were compared using receiver-operating characteristics (ROC/AUC) and calculation of biopsies that could be avoided. Results: Paper I. During a 9-year study period, 46%, 68%, and 77% of men without previous PCa and aged 50–59 years, 60–69 years, and 70–79 years, respectively, had a PSA test. The probability of retesting with PSA was PSA- and age-dependent, with a 26-month cumulative incidence of 0.34 if the first PSA value was < 1 ng/ml. Paper II. PCa was diagnosed in 47 of 172 men with PSA levels of 1‒3ng/ml (27%), with Gleason sum of ≥ 7 in 10 of them (5.8%). There was an increase in the odds ratio of 1.60 with increasing genetic risk score. The absolute difference in risk of positive biopsy was 19 percentage points, comparing the high and low genetic risk groups (37% vs. 18%). Paper III. The four-kallikrein panel showed AUCs of 69.0 when predicting PCa of any grade and 71.8 when predicting high-grade cancer (Gleason score ≥ 7). Similar values were found for PHI (70.4 and 71.1, respectively). Both models had higher AUCs than a base model with PSA value and age. Using a 10% predicted risk of high-grade PCa by the four-kallikrein panel or PHI = 39 as cutoff for biopsy saved 29% of the biopsies performed, at a cost of delayed diagnosis for 10% of the men with highgrade cancer. Paper IV. There were no significant associations between aspirin or any antidiabetic medication and the risk of PCa. Men using any statin had an increased risk of both high-grade PCa and PCa overall (OR = 1.25; OR = 1.16). Compared to men without the medication, the level of the first PSA was lower in men using aspirin, statin, metformin, or insulin. Conclusions: Although screening for PCa is not recommended in Sweden, PSA testing in Stockholm County was high in men aged over 50 years. A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA levels of 1–3 ng/ml. Furthermore, we found that two blood tests, the PHI and the four-kallikrein panel, performed similarly in predicting prostate biopsy outcome. Introduction of such risk stratification tools could increase the proportion of men being classified in line with their true risk of PCa. We found no protective effect of aspirin, statins, or antidiabetics in terms of overall risk of prostate cancer or high-grade cancer.
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