| 1. |
- Lindström, Anton, 1976-, et al.
(författare)
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Postprocessing of docked protein-ligand complexes using implicit solvation models
- 2011
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Ingår i: Journal of chemical information and modeling. - : American Chemical Society (ACS). - 1549-960X .- 1549-9596. ; 51:2, s. 267-282
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Tidskriftsartikel (refereegranskat)abstract
- Molecular docking plays an important role in drug discovery as a tool for the structure-based design of small organic ligands for macromolecules. Possible applications of docking are identification of the bioactive conformation of a protein−ligand complex and the ranking of different ligands with respect to their strength of binding to a particular target. We have investigated the effect of implicit water on the postprocessing of binding poses generated by molecular docking using MM-PB/GB-SA (molecular mechanics Poisson−Boltzmann and generalized Born surface area) methodology. The investigation was divided into three parts: geometry optimization, pose selection, and estimation of the relative binding energies of docked protein−ligand complexes. Appropriate geometry optimization afforded more accurate binding poses for 20% of the complexes investigated. The time required for this step was greatly reduced by minimizing the energy of the binding site using GB solvation models rather than minimizing the entire complex using the PB model. By optimizing the geometries of docking poses using the GBHCT+SA model then calculating their free energies of binding using the PB implicit solvent model, binding poses similar to those observed in crystal structures were obtained. Rescoring of these poses according to their calculated binding energies resulted in improved correlations with experimental binding data. These correlations could be further improved by applying the postprocessing to several of the most highly ranked poses rather than focusing exclusively on the top-scored pose. The postprocessing protocol was successfully applied to the analysis of a set of Factor Xa inhibitors and a set of glycopeptide ligands for the class II major histocompatibility complex (MHC) Aq protein. These results indicate that the protocol for the postprocessing of docked protein−ligand complexes developed in this paper may be generally useful for structure-based design in drug discovery.
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| 3. |
- Tingstedt, Bobby, et al.
(författare)
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Pancreatic Cancer, Healthcare Cost, and Loss of Productivity: A Register-based Approach.
- 2011
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 35, s. 2298-2305
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the fact that pancreatic cancer is the fourth leading cause of cancer-related death, there is little empirical evidence on its direct healthcare costs and, especially, its indirect costs due to loss of production. METHODS: The present study is a retrospective analysis of all patients with pancreatic cancer (excluding endocrine cancer) in the primary catchment area of Lund University Hospital, Sweden, during the period 2005-2007. Detailed information on all diagnostic and therapeutic investigations, interventions, and postoperative course and long-term follow-up was collected, as well as absenteeism from work due to the health problem, from which direct costs were calculated. The indirect costs for loss of production due to sickness and premature death were calculated by the human capital method. A total of 83 patients were included, for an incidence rate of 9.9 patients/100,000 inhabitants. RESULTS: Direct treatment cost per pancreatic-cancer patient was estimated at EUR 16,066 for each patient's remaining lifetime. Hospitalization accounted for the major expenditure-60% of the lifetime treatment cost. Patients with resectable tumor had a mean cost of EUR 19,809; locally advanced disease, EUR 14,899; and metastatic disease, 16,179. Younger patients and men had a higher than average lifetime treatment cost. The loss of productivity was estimated at EUR 287,420 per patient younger than 65 years of age, of which premature mortality accounted for 79%. CONCLUSIONS: Adding the cost of palliative care estimated in a previous Swedish study, health-care costs and productivity losses for pancreatic cancer would add up to a substantial economic burden for Sweden at large in 2009 (population 9.1 million), between EUR 86 million and EUR 93 million.
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| 4. |
- Ali, Alaa M. G., et al.
(författare)
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Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases
- 2014
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:6, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre-or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer-specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. (C) 2014 AACR.
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| 5. |
- Andersson, Alina, et al.
(författare)
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Analytic Parameterization of Stabilizing Controllers for the Surge Subsystem of the Moore-Greitzer Compressor Model
- 2013
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Ingår i: Proc. 2013 American Control Conference (ACC2013). - 0743-1619. - 9781479901777 ; , s. 5257-5262
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Konferensbidrag (refereegranskat)abstract
- This paper is based on a new procedure for dynamic output feedback design for systems with nonlinearities satisfying quadratic constraints. The new procedure is motivated by the challenges of output feedback control design for the 3-state Moore-Greitzer compressor model. First, we use conditions for stability of a transformed system and the associated matching conditions to find the data of the stabilizing controllers for the surge subsystem. Second, using the set of stabilizing controllers satisfying the given constraints for the closed-loop system with the dynamic output feedback controller we made optimization over the parameter set. We present the data of the stabilizing controllers and the new constraints for the corresponding parameters. The contributions in this paper are simplified conditions for the synthesis and optimization over the control parameter set.
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| 6. |
- Andersson, Alina, et al.
(författare)
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Robustness of the Moore-Greitzer Compressor Model's Surge Subsystem with New Dynamic Output Feedback Controllers
- 2014. - 3
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Ingår i: 19th IFAC World Congress. - : Elsevier. - 2405-8963. - 9783902823625 ; 47, s. 3690-3695
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Konferensbidrag (refereegranskat)abstract
- This work presents an extension of a design procedure for dynamic output feedback design for systems with nonlinearities satisfying quadratic constraints. In this work we used an axial gas compressor model described by the 3-state Moore-Greitzer compressor model (MG) that has some challenges for output feedback control design (Planovsky and Nikolaev 1990), (Rubanova 2013). The more general constraints for the investigation of the robustness with respect to parametric uncertainties and measurement noise are shown.
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| 7. |
- Andersson, Claes, 1973, et al.
(författare)
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An evolutionary developmental approach to cultural evolution
- 2014
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Ingår i: Current Anthropology. - : University of Chicago Press. - 0011-3204 .- 1537-5382. ; 55:2, s. 154-174
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Tidskriftsartikel (refereegranskat)abstract
- Evolutionary developmental theories in biology see the processes and organization of organisms as crucial for understanding the dynamic behavior of organic evolution. Darwinian forces are seen as necessary but not sufficient for explaining observed evolutionary patterns. We here propose that the same arguments apply with even greater force to culture vis-à-vis cultural evolution. In order not to argue entirely in the abstract, we demonstrate the proposed approach by combining a set of different models into a provisional synthetic theory, and by applying this theory to a number of short case studies. What emerges is a set of concepts and models that allow us to consider entirely new types of explanations for the evolution of cultures. For example we see how feedback relations - both within societies and between societies and their ecological environment - have the power to shape evolutionary history in profound ways. The ambition here is not to produce a definite statement on what such a theory should look like but rather to propose a starting point along with an argumentation and demonstration of its potential.
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| 8. |
- Andersson, Claes, 1973, et al.
(författare)
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Developing of the future: scaffolded Darwinism in societal evolution
- 2014
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Ingår i: Behavioral and Brain Sciences. - 0140-525X .- 1469-1825. ; 37:4, s. 417-418
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Tidskriftsartikel (refereegranskat)abstract
- We sympathize with the project of a synthetic approach for devising a "theory of intentional change" and agree that Darwinism should be central in such a theory. But Darwinism is not the only process of evolution that needs to be included. Evolutionary biology itself has taken such a turn recently, with the emergence of developmental evolutionary approaches.
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| 9. |
- Andersson, Claes, 1973, et al.
(författare)
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Societal Systems - Complex or worse?
- 2014
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Ingår i: Futures : The journal of policy, planning and futures studies. - : Elsevier BV. - 0016-3287. ; 63, s. 145-157
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Tidskriftsartikel (refereegranskat)abstract
- The basic observation that we explore in this paper is simple but, we argue, rich in consequences: societal systems combine two qualities that are commonly referred to as complexity and complicatedness. We address the problem that societal systems remain recalcitrant despite the development of powerful approaches for dealing with both of these qualities. The root of this problem we identify to be that the combination between complexity and complicatedness is emergent; i.e. fundamentally and irreducibly different from either quality in isolation. This means that neither class of such approaches can be expected to work well on their own. But it also means that the obvious strategy of combining theory for complexity and complicatedness may be much more challenging than envisioned. In short, systems where complexity and complicatedness is mixed ought to be treated as a distinct class of systems. Noting a connection to what has long been called "wicked problems" we hereby outline such a class of systems that we call "wicked systems". We introduce a simple model and heuristic and discuss some implications for theorizing and modeling.
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| 10. |
- Andersson, Fredrik, et al.
(författare)
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Extended structure tensors for multiple directionality estimation
- 2013
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Ingår i: Geophysical Prospecting. - : Wiley. - 1365-2478 .- 0016-8025. ; 61:6, s. 1135-1149
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Tidskriftsartikel (refereegranskat)abstract
- Standard structure tensors provide a robust way of directionality estimation of waves (or edges) but only for the case when they do not intersect. In this work, a structure tensor extension using a one-way wave equation is proposed as a tool for estimating directionality in seismic data and images in the presence of conflicting dips. Detection of two intersecting waves is possible in a two-dimensional case. In three dimensions both two and three intersecting waves can be detected. Moreover, a method for directionality filtering using the estimated directions is proposed. This method makes use of the ideas of a one-way wave equation but can be applied to generic images not related to wave propagation.
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