| 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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| 2. |
- Papadopoulos, Yiannis, et al.
(författare)
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Automatic allocation of safety integrity levels
- 2010
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Ingår i: Proceedings of the 1st Workshop on Critical Automotive applications. - New York : Association for Computing Machinery (ACM). - 9781605589152 ; , s. 7-10
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Konferensbidrag (refereegranskat)abstract
- In this paper, we describe a concept for the automatic allocationof general Safety Integrity Levels (SILs) to subsystems andcomponents of complex hierarchical networked architectures thatdeliver sets of safety critical functions. The concept is generic andcan be adapted to facilitate the safety engineering approachdefined in several standards that employ the concept of integrityor assurance levels including ISO 26262, the emergingautomotive safety standard. SIL allocation is facilitated by HiPHOPS,an automated safety analysis tool, and can be performed inthe context of development using EAST-ADL2, an automotivearchitecture description language. The process rationalizescomplex risk allocation and leads to optimal/economic allocationof SILs.
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| 3. |
- Arop, Martin Deosborns, et al.
(författare)
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Optimal Actuator Placement for Control of Vibrations Induced by Pedestrian-Bridge Interactions
- 2023
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Ingår i: MATHEMATICS IN APPLIED SCIENCES AND ENGINEERING. - : WESTERN LIBRARIES. - 2563-1926. ; 4:3, s. 172-195
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, an optimal actuator placement problem with a linear wave equation as the constraint is considered. In particular, this work presents the frameworks for finding the best location of actuators depending upon the given initial conditions, and where the dependence on the initial conditions is averaged out. The problem is motivated by the need to control vibrations induced by pedestrian-bridge interactions. An approach based on shape optimization techniques is used to solve the problem. Specifically, the shape sensitivities involving a cost functional are determined using the averaged adjoint approach. A numerical algorithm based on these sensitivities is used as a solution strategy. Numerical results are consistent with the theoretical results, in the two examples considered.
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| 4. |
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| 5. |
- Berntsson, Fredrik, 1971-, et al.
(författare)
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More on Estimation of Banded and Banded Toeplitz Covariance Matrices
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this paper we consider two different linear covariance structures, e.g., banded and bended Toeplitz, and how to estimate them using different methods, e.g., by minimizing different norms.One way to estimate the parameters in a linear covariance structure is to use tapering, which has been shown to be the solution to a universal least squares problem. We know that tapering not always guarantee the positive definite constraints on the estimated covariance matrix and may not be a suitable method. We propose some new methods which preserves the positive definiteness and still give the correct structure.More specific we consider the problem of estimating parameters of a multivariate normal p–dimensional random vector for (i) a banded covariance structure reflecting m–dependence, and (ii) a banded Toeplitz covariance structure.
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| 6. |
- Berntsson, John, et al.
(författare)
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Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke
- 2019
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:7, s. 553-558
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular endothelial growth factor D (VEGF-D) has important functions in lymphangiogenesis and angiogenesis. High plasma levels of VEGF-D have been associated with incidence of heart failure. The association of VEGF-D with atrial fibrillation (AF) and stroke is unclear and we hypothesised that VEGF-D could also be associated with incidence of AF and ischaemic stroke. Methods: VEGF-D was measured in fasting blood samples of 4689 subjects (40% men) without a history of AF from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Median age was 58 years (range 46-68). Cox regression analyses, adjusted for multiple risk factors, was used to assess AF and ischaemic stroke risk in relation to VEGF-D levels. Results: During a median follow-up time of 20.6 years, there were 637 cases of incident AF and 322 cases of first ischaemic stroke. After adjustment, VEGF-D was significantly associated with AF (HR 1.13(95% CI 1.04 to 1.23) per 1 SD increase) and ischaemic stroke (HR 1.14(95% CI 1.02 to 1.28) per 1 SD). The association with ischaemic stroke was explained by an increased incidence of AF-related stroke. HRs per 1 SD were 1.34 (95% CI 1.04 to 1.71) for AF-related ischaemic stroke and 1.04 (95% CI 0.90 to 1.19) for ischaemic stroke without AF. Conclusions: Increased VEGF-D concentrations were associated with AF and ischaemic stroke. The relationship with ischaemic stroke was more pronounced in subjects with a diagnosis of AF.
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| 7. |
- Berntsson, Lars-Olof, et al.
(författare)
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EAST-ADL 2.0 Specification
- 2008
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Rapport (refereegranskat)abstract
- This specification of the EAST ADL 2.0 is based on the EAST-ADL developed in the EAST EEA projectand has been further refined and harmonized with on-going modelling appraches in the automotiveindustry. It presents the modeling infrastructure, i.e. how the modeling elements should be represented inthe language and the UML representation. For each package a usage example is provided.The EAST-ADL 2.0 is harmonized with AUTOSAR.The metamodel and UML profile of EAST ADL 2.0 is defined in two steps: A domain (automotive)metamodel is defined, capturing only the domain specific needs of the language, without adding the UML2details. The basic concepts of UML are used for this purpose, such as classes, compositions andassociations. Based on the domain metamodel, a UML2 profile for the domain metamodel is defined,specifying stereotypes with properties and constraints.Comments on the content of this document are welcomed, and should be directed to .Please download the latest available specification and the XMI file ready for use in UML2 tools from the website.
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| 8. |
- Berntsson, Ronnie P. -A., et al.
(författare)
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Structural insight into DNA binding and oligomerization of the multifunctional Cox protein of bacteriophage P2
- 2014
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 42:4, s. 2725-2735
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Tidskriftsartikel (refereegranskat)abstract
- The Cox protein from bacteriophage P2 is a small multifunctional DNA-binding protein. It is involved in site-specific recombination leading to P2 prophage excision and functions as a transcriptional repressor of the P2 Pc promoter. Furthermore, it transcriptionally activates the unrelated, defective prophage P4 that depends on phage P2 late gene products for lytic growth. In this article, we have investigated the structural determinants to understand how P2 Cox performs these different functions. We have solved the structure of P2 Cox to 2.4 angstrom resolution. Interestingly, P2 Cox crystallized in a continuous oligomeric spiral with its DNA-binding helix and wing positioned outwards. The extended C-terminal part of P2 Cox is largely responsible for the oligomerization in the structure. The spacing between the repeating DNA-binding elements along the helical P2 Cox filament is consistent with DNA binding along the filament. Functional analyses of alanine mutants in P2 Cox argue for the importance of key residues for protein function. We here present the first structure from the Cox protein family and, together with previous biochemical observations, propose that P2 Cox achieves its various functions by specific binding of DNA while wrapping the DNA around its helical oligomer.
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| 9. |
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| 10. |
- Berntsson, Thore, 1947, et al.
(författare)
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Research activities on heat transformers at Chalmers University of Technology
- 1988
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Ingår i: Commission of the European Communities, Absorption heat pumps, Proceedings of a workshop held in London 12 - 14 April 1988.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Ongoing and planned research work in the absorption field at Chalmers University of Technology can be divided into four areas:- System studies and optimization;A computer program has been developed with which a heat transformer can be simulated and its parts can be technically and/or economically optimized. Technical optimizations include optimal area distribution between the five heat exchangers to achieve a certain COP or a certain temperature lift and minimum total area needed for a certain heat output. Economic optimizations include optimal size of the heat transformer and its components at various conditions.- Desorption heat transfer; An experimental plant for studies of heat transfer coefficients of LiBr-H20 in a falling-film type desorber has been constructed. No results are yet available. -An activity-coefficient model for electrolyte systems; An activity-coefficient has been proposed to represent the properties over a wide electrolyte concentration range, i.e. high dilution to the solubility limit. It is well suited both for single-electrolyte and multi-electrolyte solutions.-Transport properties for electrolyte systems;The aim with this project is to develop methods and equations for correlation and prediction of transport properties, mainly viscosity, for single- and multicomponent electrolyte systems. An equation for correlation of viscosity data has been proposed and an equation for prediction of the viscosity based on activity coefficients is under development.
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