| 1. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 5. |
- Brax, Christoffer, et al.
(författare)
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Evaluating Precise and Imprecise State-Based Anomaly Detectors for Maritime Surveillance
- 2010
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Ingår i: Proceedings of the 13th International Conference on Information Fusion. - : IEEE. - 9780982443811 ; , s. Article number 5711997-
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Konferensbidrag (refereegranskat)abstract
- We extend the State-Based Anomaly Detection approach by introducing precise and imprecise anomaly detectors using the Bayesian and credal combination operators, where evidences over time are combined into a joint evidence. We use imprecision in order to represent the sensitivity of the classification regarding an object being normal or anomalous. We evaluate the detectors on a real-world maritime dataset containing recorded AIS data and show that the anomaly detectors outperform previously proposed detectors based on Gaussian mixture models and kernel density estimators. We also show that our introduced anomaly detectors perform slightly better than the State-Based Anomaly Detection approach with a sliding window.
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| 6. |
- Garpebring, Anders, et al.
(författare)
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Uncertainty estimation in dynamic contrast-enhanced MRI
- 2013
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Ingår i: Magnetic Resonance in Medicine. - : Wiley-Blackwell. - 0740-3194 .- 1522-2594. ; 69:4, s. 992-1002
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Tidskriftsartikel (refereegranskat)abstract
- Using dynamic contrast-enhanced MRI (DCE-MRI), it is possible to estimate pharmacokinetic (PK) parameters that convey information about physiological properties, e.g., in tumors. In DCE-MRI, errors propagate in a nontrivial way to the PK parameters. We propose a method based on multivariate linear error propagation to calculate uncertainty maps for the PK parameters. Uncertainties in the PK parameters were investigated for the modified Kety model. The method was evaluated with Monte Carlo simulations and exemplified with in vivo brain tumor data. PK parameter uncertainties due to noise in dynamic data were accurately estimated. Noise with standard deviation up to 15% in the baseline signal and the baseline T1 map gave estimated uncertainties in good agreement with the Monte Carlo simulations. Good agreement was also found for up to 15% errors in the arterial input function amplitude. The method was less accurate for errors in the bolus arrival time with disagreements of 23%, 32%, and 29% for Ktrans, ve, and vp, respectively, when the standard deviation of the bolus arrival time error was 5.3 s. In conclusion, the proposed method provides efficient means for calculation of uncertainty maps, and it was applicable to a wide range of sources of uncertainty.
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| 12. |
- Jansson, Ronnie, et al.
(författare)
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Recombinant Spider Silk Genetically Functionalized with Affinity Domains
- 2014
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 15:5, s. 1696-1706
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Tidskriftsartikel (refereegranskat)abstract
- Functionalization of biocompatible materials for presentation of active protein domains is an area of growing interest. Herein, we describe a strategy for functionalization of recombinant spider silk via gene fusion to affinity domains of broad biotechnological use. Four affinity domains of different origin and structure; the IgG-binding domains Z and C2, the albumin-binding domain ABD, and the biotin-binding domain M4, were all successfully produced as soluble silk fusion proteins under nondenaturing purification conditions. Silk films and fibers produced from the fusion proteins were demonstrated to be chemically and thermally stable. Still, the bioactive domains are concluded to be folded and accessible, since their respective targets could be selectively captured from complex samples, including rabbit serum and human plasma. Interestingly, materials produced from mixtures of two different silk fusion proteins displayed combined binding properties, suggesting that tailor-made materials with desired stoichiometry and surface distributions of several binding domains can be produced. Further, use of the IgG binding ability as a general mean for presentation of desired biomolecules could be demonstrated for a human vascular endothelial growth factor (hVEGF) model system, via a first capture of anti-VEGF IgG to silk containing the Z-domain, followed by incubation with hVEGF. Taken together, this study demonstrates the potential of recombinant silk, genetically functionalized with affinity domains, for construction of biomaterials capable of presentation of almost any desired biomolecule.
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| 13. |
- Johansson, Ronnie, et al.
(författare)
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Information Acquisition Strategies for Bayesian Network-based Decision Support
- 2010
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Ingår i: FUSION 2010. - : IEEE conference proceedings. - 9780982443811 ; , s. 1-8
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Konferensbidrag (refereegranskat)abstract
- Determining how to utilize information acquisition resources optimally is a difficult task in the intelligence domain. Nevertheless, an intelligence analyst can expect little or no support for this from software tools today. In this paper, we describe a proof of concept implementation of a resource allocation mechanism for an intelligence analysis support system. The system uses a Bayesian network to structure intelligence requests, and the goal is to minimize the uncertainty of a variable of interest. A number of allocation strategies are discussed and evaluated through simulations.
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| 15. |
- Karlsson, Alexander, et al.
(författare)
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An Empirical Comparison of Bayesian and Credal Combination Operators
- 2010
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Ingår i: FUSION 2010. - : IEEE conference proceedings. - 9780982443811 ; , s. Article number 5711907-
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Konferensbidrag (refereegranskat)abstract
- We are interested in whether or not representing and maintaining imprecision is beneficial when combining evidences from multiple sources. We perform two experiments that contain different levels of risk and where we measure the performance of the Bayesian and credal combination operators by using a simple score function that measures the informativeness of a reported decision set. We show that the Bayesian combination operator performed on centroids of operand credal sets outperforms the credal combination operator when no risk is involved in the decision problem. We also show that if a risk component is present in the decision problem, a simple cautious decision policy for the Bayesian combination operator can be constructed that outperforms the corresponding credal decision policy.
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| 16. |
- Karlsson, Alexander, et al.
(författare)
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An Empirical Comparison of Bayesian and Credal Set Theory for Discrete State Estimation
- 2010
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Ingår i: Information Processing and Management of Uncertainty in Knowledge-Based Systems. Theory and Methods. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642140549 - 9783642140556 - 3642140548 ; , s. 80-89
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Konferensbidrag (refereegranskat)abstract
- We are interested in whether or not there exist any advantages of utilizing credal set theory for the discrete state estimation problem. We present an experiment where we compare in total six different methods, three based on Bayesian theory and three on credal set theory. The results show that Bayesian updating performed on centroids of operand credal sets significantly outperforms the other methods. We analyze the result based on degree of imprecision, position of extreme points, and second-order distributions.
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| 17. |
- Karlsson, Alexander, et al.
(författare)
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Characterization and Empirical Evaluation of Bayesian and Credal Combination Operators
- 2011
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Ingår i: Journal of Advances in Information Fusion. - : ISIF, International Society of Information Fusion. - 1557-6418. ; 6:2, s. 150-166
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Tidskriftsartikel (refereegranskat)abstract
- We address the problem of combining independent evidences from multiple sources by utilizing the Bayesian and credal combination operators. We present measures for degree of conflict and imprecision, which we use in order to characterize the behavior of the operators through a number of examples. We introduce discounting operators that can be used whenever information about the reliability of sources is available. The credal discounting operator discounts a credal set with respect to an interval of reliability weights, hence, we allow for expressing reliability of sources imprecisely. We prove that the credal discounting operator can be computed by using the extreme points of its operands. We also perform two experiments containing different levels of risk where we compare the performance of the Bayesian and credal combination operators by using a simple score function that measures the informativeness of a reported decision set. We show that the Bayesian combination operator performed on centroids of operand credal sets outperforms the credal combination operator when no risk is involved in the decision problem. We also show that if a risk component is present in the decision problem, a simple cautious decision policy for the Bayesian combination operator can be constructed that outperforms the corresponding credal decision policy.
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| 18. |
- Karlsson, Alexander
(författare)
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Evaluating credal set theory as a belief framework in high-level information fusion for automated decision-making
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High-level information fusion is a research field in which methods for achieving an overall understanding of the current situation in an environment of interest are studied. The ultimate goal of these methods is to provide effective decision-support for human or automated decision-making. One of the main proposed ways of achieving this is to reduce the uncertainty, coupled with the decision, by utilizing multiple sources of information. Handling uncertainty in high-level information fusion is performed through a belief framework, and one of the most commonly used such frameworks is based on Bayesian theory. However, Bayesian theory has often been criticized for utilizing a representation of belief and evidence that does not sufficiently express some types of uncertainty. For this reason, a generalization of Bayesian theory has been proposed, denoted as credal set theory, which allows one to represent belief and evidence imprecisely. In this thesis, we explore whether credal set theory yields measurable advantages, compared to Bayesian theory, when used as a belief framework in high-level information fusion for automated decision-making, i.e., when decisions are made by some pre-determined algorithm. We characterize the Bayesian and credal operators for belief updating and evidence combination and perform three experiments where the Bayesian and credal frameworks are evaluated with respect to automated decision-making. The decision performance of the frameworks are measured by enforcing a single decision, and allowing a set of decisions, based on the frameworks’ belief and evidence structures. We construct anomaly detectors based on the frameworks and evaluate these detectors with respect to maritime surveillance. The main conclusion of the thesis is that although the credal framework uses considerably more expressive structures to represent belief and evidence, compared to the Bayesian framework, the performance of the credal framework can be significantly worse, on average, than that of the Bayesian framework, irrespective of the amount of imprecision.
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| 19. |
- Lätt, Jimmy, et al.
(författare)
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Regional values of diffusional kurtosis estimates in the healthy brain.
- 2013
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1522-2586 .- 1053-1807. ; 37:3, s. 610-618
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To provide estimates of the diffusional kurtosis in the healthy brain in anatomically defined areas and list these along previously reported values in pathologies. MATERIALS AND METHODS: Thirty-six volunteers (mean age = 33.1 years; range, 19-64 years) underwent diffusional kurtosis imaging. Mean kurtosis (MK), radial kurtosis (RK), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA) were determined in 26 anatomical structures. Parameter estimates were assessed regarding age dependence. RESULTS: MK varied from 1.38 in the splenium of the corpus callosum to 0.66 in the caudate head, MD varied from 0.68 to 0.62 μm(2) /ms and FA from 0.87 to 0.29. MK, and FA showed a strong positive correlation, RK and RD a strong negative correlation. Parameter estimates showed age correlation in some regions; also the average MK and RK for all WM and all GM areas, respectively, were negatively correlated with age. CONCLUSION: DKI parameter estimates MK and RK varied depending on the anatomical region and varied with age in pooled WM and GM data. MK estimates in the internal capsule, corpus callosum, and thalamus were consistent with previous studies. The range of values of MK and RK in healthy brain overlapped with that in pathologies. J. Magn. Reson. Imaging 2012. © 2012 Wiley Periodicals, Inc.
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| 21. |
- Müller, Christian, et al.
(författare)
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Functionalisation of recombinant spider silk with conjugated polyelectrolytes
- 2011
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Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry. - 0959-9428 .- 1364-5501. ; 21:9, s. 2909-2915
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Tidskriftsartikel (refereegranskat)abstract
- Conjugated polyelectrolytes are demonstrated to permit facile staining of recombinant spider silk fibres. We find that the polyelectrolyte concentration and pH of the staining solution as well as the incubation temperature strongly influence the efficiency of this self-assembly process, which appears to be principally mediated through favourable electrostatic interactions. Thus, depending on the choice of staining conditions as well as the polyelectrolyte, electrically conductive or photoluminescent recombinant silk fibres could be produced. In addition, staining of natural Bombyx mori silk is established, which emphasises the versatility of the here advanced approach to functionalise silk-based materials.
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| 22. |
- Riveiro, Maria, 1978-, et al.
(författare)
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Modeling and analysis of energy data : state-of-the-art and practical results from an application scenario
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper presents a comprehensive summary of the state-of-the-art of energy efficiency research. The literature review carried out focuses on the application of data mining and data analysis techniques to energy consumption data, as well as descriptions of tools, applications and research prototypes to manage the consumption of energy. Moreover, preliminary results of the application of a clustering technique to energy consumption data illustrate the review.
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