| 1. |
- Berghauser Pont, Meta, 1972, et al.
(författare)
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PST
- 2019
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Annan publikation (mjukvara/multimedium) (övrigt vetenskapligt/konstnärligt)abstract
- PST is a tool for performing space syntax and regular accessibility analyses. It currently consists of two main parts - a C++ and Python library called Pstalgo and a plugin for the desktop application QGIS.PST is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version. The GNU General Public License is intended to guarantee your freedom to share and change all versions of a program--to make sure it remains free software for all its users.For latest download visit either the Chalmers publication page, or find "Releases" on the Github page.
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| 2. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 3. |
- Gasch, Tobias
(författare)
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Concrete as a multi-physical material with applications to hydro power facilities
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During its lifetime, a concrete structure is subjected to many different actions, ranging from mechanical loads to environmental actions. To accurately predict its integrity from casting and throughout its service life, a modelling strategy is required that considers mechanical loading but also implicitly accounts for physical effects such as temperature and moisture variations. This is especially true for large concrete structures found in many infrastructure applications such as bridges, nuclear power plants and dams. Modelling concrete as a multi-physical material is becoming an increasingly used approach for which large research efforts are being made, including the development of more refined mathematical and numerical methods as well as considering more physical and chemical variables in the coupled model.The research project, of which this licentiate thesis is the first phase, aims at investigating aging concrete structures at hydro power facilities, with focus on the internal structures of the power plants. This thesis presents a review of advanced mathematical methods and concepts for modelling aging concrete found in the literature which can later be applied to study such structures. The focus is on models that describe the deformational behaviour of concrete where aspects such as aging, cracking, creep and shrinkage are investigated. However, in order to accurately describe such phenomena, a multi-physical approach is adopted where moisture and temperature variations in the concrete are studied. Also, models that describe the chemical behaviour related to hydration and thus in extension aging, are also reviewed and introduced in the multi-physical framework. The use of such models are discussed in the context of the finite element method (FEM), in which coupled models are implemented, verified and applied in the appended papers using two different FE codes.Several verification examples are presented covering different aspects of the implemented models, both in isolation and coupled in a multi-physical setting. By comparing the numerical results with experimental data from the literature it can be shown that it is possible to predict most aspects of aging concrete that have been of interest here. While these examples are all on a laboratory scale, numerical examples and case studies are also provided that exemplify how the models can be applied on a structural scale. By using the developed analysis tools, valuable information and insights can be gained on aging concrete structures and these tools will in the next phase of the research project be applied to large concrete structures at hydro power facilities.
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| 4. |
- Gasch, Tobias
(författare)
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Multiphysical analysis methods to predict the ageing and durability of concrete
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With the societal demand for sustainability and the increasing age of infrastructure, a crucial task for the civil engineering community is to improve the durability of concrete structures. This thesis aims to contribute to such development through theoretical studies using mathematical modelling and numerical simulations. During its service life, a concrete structure is subjected to many different actions, ranging from mechanical loads to chemical and physical processes. Hence, a sound modelling strategy requires multiphysics and the inclusion of coupled chemical and physical fields (e.g. temperature, moisture and cement hydration) in addition to methods that describe mechanical integrity of the material. Conditions and phenomena critical for concrete structures at hydropower facilities have been of particular interest to study.The thesis presents several mathematical models of various complexity to describe the multiphysical behaviour of concrete using a material point description. A significant focus is on models that describe the mechanical behaviour of concrete where aspects such as ageing, cracking, creep and shrinkage are investigated. For the creep behaviour, a state-of-the-art model based on the Microprestress–Solidification (MPS) theory is reviewed and further developed. The appended papers (III to IV) presents a mathematical framework for the modelling of durability aspects of concrete based on multiphase porous media theory. The governing equations are derived with the Thermodynamically Constrained Averaging Theory (TCAT) as a starting point. It is demonstrated how this framework can be applied to a broad variety of phenomena related to durability; from the casting and hardening of concrete to the long-term absorption of water into air-entrained concrete. The Finite Element Methods (FEM) is used to solve the proposed mathematical models, and their capabilities are verified using experimental data from the literature.The main research contribution is the development and evaluation of theoretical models that advance the understanding and improve knowledge of the ageing and durability of concrete and concrete structures. More precisely, it is shown how multiphysical models and the developed multiphase framework can be used to gain insights on the material behaviour of concrete at smaller scales while they are also applicable to structural-scale simulations. During all model development, the efficient solution of structural problems has been fundamental. Through case studies and several examples from the literature, it is exemplified how these models can be used to enhance the performance and thereby increase the durability of concrete structures.
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| 5. |
- Gasch, Tobias, et al.
(författare)
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Non-linear analyses of cracks in aging concrete hydro power structures
- 2016
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Ingår i: Dam Engineering. - : International Water Power & Dam Construction. - 0958-9341.
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Annan publikation (populärvet., debatt m.m.)abstract
- The concrete structures at Swedish hydro power facilities were built during the early to mid-20th century and many of them are starting to exhibit age related wear and deterioration. It isimportant to ensure the integrity of these concrete structures from a dam safety perspectiveand also to secure a safe operation of the power facility in the future. With the latter in mind,this paper aims to study the concrete structures that house the power generating machinery ofthe facility, especially the parts close to the generator where the loads from the power unit aresupported. Cracks observed in these structures will reduce its stiffness, which affects theoperation of the rotating machinery. This paper presents and discusses some generalconsiderations and loads that are of importance for this type of structures and highlights sometypical cracks that have been observed in Swedish hydro power facilities. To complement thisdiscussion, a case study is presented of a hydro power facility where cracks have been foundin the concrete support structure of the power unit, especially at the interconnections betweenthe unit and the concrete. The most likely cause of these cracks are investigated through nonlinearfinite element analysis considering mechanical loads as well as physical loads such asdrying shrinkage and temperature variations. It is concluded that the long-term physicalloading is the most probable cause of the observed cracks. However, the operation of thepower unit and changes in its operational pattern can cause further propagation of thesecracks. Finally, suggestions on possible enhancement of the analysis methods used in the casestudy are proposed and discussed for further studies of this type of concrete structures.
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| 6. |
- 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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| 7. |
- 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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