| 1. |
- Aalto-Setälä, Katriina, et al.
(författare)
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Genetic risk factors and ischemic cerebrovascular disease : role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme
- 1998
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Ingår i: Annals of Medicine. - 0785-3890 .- 1365-2060. ; 30:2, s. 224-33
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Tidskriftsartikel (refereegranskat)abstract
- DNA polymorphisms in genes encoding apolipoproteins (apo) A-I, C-III, B and E and angiotensin-converting enzyme (ACE) have been proposed to be associated with the risk of coronary artery disease (CAD). We studied whether the same genetic markers would also be associated with the occurrence and extent of atherosclerosis in cervical arteries. DNA samples from 234 survivors of stroke or a transient ischaemic attack aged 60 years or less were examined. The presence of atherosclerosis was assessed using aortic arch angiograms. The SstI polymorphism of apoA-I/C-III gene locus, the XbaI polymorphism of apoB gene, common apoE phenotypes and the insertion/deletion polymorphism of the ACE gene were analysed. The allele frequencies of the apoA-I/C-III, apoB, apoE or ACE gene did not differ between the groups with (n = 148) or without (n = 85) cervical atherosclerosis. However, when patients with at least one apoE4 allele and one X2 allele of apoB were combined and compared with those without either of them (E2E3 or E3E3 and X1X1), a significant association with the presence of cervical atherosclerosis was found (P = 0.03). The patients having the E2E3 phenotype had a significantly elevated serum triglyceride level compared with those with the E3E3 phenotype (P = 0.03). Serum high-density lipoprotein (HDL) cholesterol was lower in the patients with the E2E3 phenotype than in those with the E3E3 and E3E4 (P = 0.01 and P = 0.06, respectively). The apoB or ACE genotypes were not significantly associated with serum lipid or lipoprotein levels. There was no association between the ACE gene polymorphism and the occurrence of hypertension. In conclusion, the interaction of common apoB and apoE alleles may increase the risk of atherosclerosis in cervical arteries.
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| 2. |
- Aittokoski, Timo, et al.
(författare)
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Clustering aided approach for decision making in computationally expensive multiobjective optimization
- 2009
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Ingår i: Optimization Methods and Software. - : Informa UK Limited. - 1055-6788 .- 1029-4937. ; 24:2, s. 157-174
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Tidskriftsartikel (refereegranskat)abstract
- Typically, industrial optimization problems need to be solved in an efficient, multiobjective and global manner, because they are often computationally expensive (as function values are typically based on simulations), they may contain multiple conflicting objectives, and they may have several local optima. Solving such problems may be challenging and time consuming when the aim is to find the most preferred Pareto optimal solution. In this study, we propose a method where we use an advanced clustering technique to reveal essential characteristics of the approximation of the Pareto optimal set, which has been generated beforehand. Thus, the decision maker (DM) is involved only after the most time consuming computation is finished. After the initiation phase, a moderate number of cluster prototypes projected to the Pareto optimal set is presented to the DM to be studied. This allows him/her to rapidly gain an overall understanding of the main characteristics of the problem without placing too much cognitive load on the DM. Furthermore, we also suggest some ways of applying our approach to different types of problems and demonstrate it with an example related to internal combustion engine design.
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| 3. |
- Aittokoski, Timo, et al.
(författare)
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Cost Effective Simulation-Based Multiobjective Optimization in Performance of Internal Combustion Engine
- 2008
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Ingår i: Engineering optimization (Print). - : Informa UK Limited. - 0305-215X .- 1029-0273. ; 40:7, s. 593-612
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Tidskriftsartikel (refereegranskat)abstract
- Solving real-life engineering problems requires often multiobjective, global, and efficient (in terms of objective function evaluations) treatment. In this study, we consider problems of this type by discussing some drawbacks of the current methods and then introduce a new population-based multiobjective optimization algorithm UPS-EMOA which produces a dense (not limited to the population size) approximation of the Pareto-optimal set in a computationally effective manner.
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| 4. |
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| 5. |
- Aittokoski, Timo, et al.
(författare)
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Efficient Evolutionary Method to Approximate the Pareto Optimal Set in Multiobjective Optimization
- 2008
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Ingår i: Proceedings of the International Conference on Engineering Optimization EngOpt 2008.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Solving real-life engineering problems requires often multiobjective, global and efficient (in terms of ob-jective function evaluations) treatment. In this study, we consider problems of this type by discussingsome drawbacks of the current methods and then introduce a new population based multiobjective op-timization algorithm which produces a dense (not limited to the population size) approximation of thePareto optimal set in a computationally effective manner.
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| 6. |
- Ibrahim, Hazem, et al.
(författare)
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RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function
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Ingår i: Diabetologia. - 0012-186X.
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Regulatory factor X 6 (RFX6) is crucial for pancreatic endocrine development and differentiation. The RFX6 variant p.His293LeufsTer7 is significantly enriched in the Finnish population, with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 and gestational diabetes. However, the precise mechanism of this predisposition remains unknown. Methods: To understand the role of this variant in beta cell development and function, we used CRISPR technology to generate allelic series of pluripotent stem cells. We created two isogenic stem cell models: a human embryonic stem cell model; and a patient-derived stem cell model. Both were differentiated into pancreatic islet lineages (stem-cell-derived islets, SC-islets), followed by implantation in immunocompromised NOD-SCID-Gamma mice. Results: Stem cell models of the homozygous variant RFX6−/− predictably failed to generate insulin-secreting pancreatic beta cells, mirroring the phenotype observed in Mitchell–Riley syndrome. Notably, at the pancreatic endocrine stage, there was an upregulation of precursor markers NEUROG3 and SOX9, accompanied by increased apoptosis. Intriguingly, heterozygous RFX6+/− SC-islets exhibited RFX6 haploinsufficiency (54.2% reduction in protein expression), associated with reduced beta cell maturation markers, altered calcium signalling and impaired insulin secretion (62% and 54% reduction in basal and high glucose conditions, respectively). However, RFX6 haploinsufficiency did not have an impact on beta cell number or insulin content. The reduced insulin secretion persisted after in vivo implantation in mice, aligning with the increased risk of variant carriers to develop diabetes. Conclusions/interpretation: Our allelic series isogenic SC-islet models represent a powerful tool to elucidate specific aetiologies of diabetes in humans, enabling the sensitive detection of aberrations in both beta cell development and function. We highlight the critical role of RFX6 in augmenting and maintaining the pancreatic progenitor pool, with an endocrine roadblock and increased cell death upon its loss. We demonstrate that RFX6 haploinsufficiency does not affect beta cell number or insulin content but does impair function, predisposing heterozygous carriers of loss-of-function variants to diabetes. Data availability: Ultra-deep bulk RNA-seq data for pancreatic differentiation stages 3, 5 and 7 of H1 RFX6 genotypes are deposited in the Gene Expression Omnibus database with accession code GSE234289. Original western blot images are deposited at Mendeley (https://data.mendeley.com/datasets/g75drr3mgw/2). Graphical Abstract: (Figure presented.).
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| 7. |
- Laukkanen, Timo, et al.
(författare)
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Bilevel heat exchanger network synthesis with an interactive multi-objective optimization method
- 2012
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Ingår i: Applied Thermal Engineering. - : Elsevier BV. - 1359-4311 .- 1873-5606. ; 48, s. 301-316
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Tidskriftsartikel (refereegranskat)abstract
- Heat exchanger network synthesis (HENS) has been an active research area for more than 40 years because well-designed heat exchanger networks enable heat recovery in process industries in an energy-and cost-efficient manner. Due to ever increasing global competition and need to decrease the harmful effects done on the environment, there still is a continuous need to improve the heat exchanger networks and their synthesizing methods. In this work we present a HENS method that combines an interactive multi-objective optimization method with a simultaneous bilevel HENS method, where the bilevel part of the method is based on grouping of process streams and building aggregate streams from the grouped streams. This is done in order to solve medium-sized industrial HENS problems efficiently with good final solutions. The combined method provides an opportunity to solve HENS problems efficiently also regarding computing effort and at the same time optimizing all the objectives of HENS simultaneously and in a genuine multi-objective manner without using weighting factors. This enables the designer or decision maker to be in charge of the design procedure and guide the search into areas that the decision maker is most interested in. Two examples are solved with the proposed method. The purpose of the first example is to help in illustrating the steps in the overall method. The second example is obtained from the literature.
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| 8. |
- Marabita, Francesco, et al.
(författare)
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Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health
- 2022
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Ingår i: Cell Systems. - : Cell Press. - 2405-4712 .- 2405-4720. ; 13:3, s. 241-255.e7
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Tidskriftsartikel (refereegranskat)abstract
- We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects. For example, ethinyl estradiol, a common oral contraceptive, produced characteristic molecular and physiological effects, including increased levels of inflammation and impact on thyroid, cortisol levels, and pulse, that were distinct from other sources of variability observed in our study. In total, this work illustrates the value of combining deep molecular and digital monitoring of human health. A record of this paper's transparent peer review process is included in the supplemental information.
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| 9. |
- Miettinen, Kaisa, 1965-, et al.
(författare)
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Efficient Evolutionary Approach to Approximate the Pareto Optimal Set in Multiobjective Optimization, UPS-EMOA
- 2010
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Ingår i: Optimization Methods and Software. - : Taylor & Francis. - 1055-6788 .- 1029-4937. ; 25:6, s. 841-858
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Tidskriftsartikel (refereegranskat)abstract
- Solving real-life engineering problems requires often multiobjective, global, and efficient (in terms of objective function evaluations) treatment. In this study, we consider problems of this type by discussing some drawbacks of the current methods and then introduce a new population-based multiobjective optimization algorithm UPS-EMOA which produces a dense (not limited to the population size) approximation of the Pareto-optimal set in a computationally effective manner.
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| 10. |
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