| 1. |
- Mälarstig, Anders, et al.
(författare)
-
Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.
|
|
| 2. |
- Bonagas, Nadilly, et al.
(författare)
-
Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
-
Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
-
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.
|
|
| 3. |
- Candel, Melissa, 1994-
(författare)
-
Co-Developing Sustainability Requirements : Exploring client and municipal perspectives in housing development
- 2020
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Construction has major environmental, social and economic impacts. Improving sustainability both during and after the construction process is widely discussed among a slew of practitioners, governments and researchers. Construction clients, such as housing developers, are considered key actors for change and innovation because of their position to set requirements when procuring construction projects. The process of developing project requirements has therefore mainly been studied during the construction clients’ procurement process. At the same time, municipalities use their position as land owners to drive sustainable development. Land allocation agreements allow municipalities to set project-specific sustainability requirements for construction projects on municipal land. The purpose of this thesis is to explore how municipal sustainability requirements affect housing developers when planning and designing their projects.The research is based on a single empirical case study of an urban development programme comprising multiple parallel and sequential housing construction projects. In this study, the municipality’s and housing developers’ perspectives are explored. The results demonstrate that the housing developers perceive several barriers to implementing municipal sustainability requirements. The three main barriers that were identified are reduced flexibility coupled with uncertainty, conflicting interests coupled with reduced autonomy and interdependencies, and a lack of trust and transparency coupled with interdependencies. The municipal sustainability requirements are initially developed by the municipality for the land allocation agreement. They are then co-developed further by the municipality and the housing developers together through negotiations before being finalised in conjunction with the developers’ procurement process.The study is focused on the period following the housing developers’ signing of land allocation agreements with the municipality and before starting their procurement process. During this period, the housing developers attempt to negotiate municipal sustainability requirements that they anticipate will increase costs, risk and uncertainty and decrease the value of their final product. Negotiations between the housing developers and the municipality can be viewed as value co-creation processes stimulated by functional conflict. These findings build on three papers that are included in the thesis.Contributions are made to literature on the role of construction clients and their perceived barriers to implementing and developing sustainable construction solutions and practices and barriers to change in general. Theoretical contributions are also made to literature on value co-creation in construction by illustrating how clients engage in the co-creation of value with municipalities and other clients. Finally, the theoretical link between value co-creation and functional conflict is studied and developed.
|
|
| 4. |
- Candel, Melissa, 1994-, et al.
(författare)
-
Front-end value co-creation in housing development projects
- 2021
-
Ingår i: Construction Management and Economics. - : Informa UK Limited. - 0144-6193 .- 1466-433X. ; 39:3, s. 245-260
-
Tidskriftsartikel (refereegranskat)abstract
- As a result of local governance, municipalities and housing developers work together to define housing development projects and to co-create value propositions. The purpose of this study is to explore how value propositions are co-created during the front-end of housing development projects and how this affects housing developers’ ability to drive change and innovation. The value co-creation process is explored through interviews, documents and observations in a case study of an urban development programme in Sweden. The findings illustrate how emerging conflicts and the process of resolving them are central drivers for value co-creation between these actors. However, conflicts that are not managed and resolved constructively can lead to the co-destruction of value. In this study we illustrate how value co-creation processes that precede procurement limit the flexibility of housing developers and determine the scope for value that can be realised.
|
|
| 5. |
- Domeij, Rickard, 1958-, et al.
(författare)
-
Exploring the archives for textual entry points to speech - Experiences of interdisciplinary collaboration in making cultural heritage accessible for research
- 2020
-
Ingår i: CEUR Workshop Proceedings. - Riga : CEUR-WS. ; , s. 45-55, s. 45-55
-
Konferensbidrag (refereegranskat)abstract
- Tilltal (Tillgängligt kulturarv för forskning i tal, 'Accessible cultural heritage for speech research') is a multidisciplinary and methodological project undertaken by the Institute of Language and Folklore, KTH Royal Institute of Technology, and The Swedish National Archives in cooperation with the National Language Bank and SWE-CLARIN [1]. It aims to provide researchers better access to archival audio recordings using methods from language technology. The project comprises three case studies and one activity and usage study. In the case studies, actual research agendas from three different fields (ethnology, sociolinguistics and interaction analysis) serve as a basis for identifying procedures that may be simplified with the aid of digital tools. In the activity and usage study, we are applying an activity-theoretical approach with the aim of involving researchers and investigating how they use - and would like to be able to use - the archival resources at ISOF. Involving researchers in participatory design ensures that digital solutions are suggested and evaluated in relation to the requirements expressed by researchers engaged in specific research tasks [2]. In this paper we focus on one of the case studies, which investigates the process by which personal experience narratives are transformed into cultural heritage [3], and account for our results in exploring how different types of text material from the archives can be used to find relevant sections of the audio recordings. Finally, we discuss what lessons can be learned, and what conclusions can be drawn, from our experiences of interdisciplinary collaboration in the project.
|
|
| 6. |
- Ekeskär, Andreas, 1984-, et al.
(författare)
-
Construction logistics in a multi-project context: coopetition among main contractors and the role of third-party logistics providers
- 2022
-
Ingår i: Construction Management and Economics. - : Taylor & Francis. - 0144-6193 .- 1466-433X. ; 40:1, s. 25-40
-
Tidskriftsartikel (refereegranskat)abstract
- As a part of supply chain management (SCM) initiatives to improve performance and productivity in construction projects, the use of construction logistics setups (CLSs) operated by third-party logistics (TPL) providers have increased. CLSs are often used in complex multi-project contexts, such as urban development districts, where extensive coordination of actors, resources, and activities is needed. The purpose of this paper is twofold: to investigate how main contractors engage in horizontal relationships with each other when coordinating activities and resources within and across projects in a multi-project context, and to investigate what role a TPL provider assumes when engaging in relationships with main contractors in a multi-project context. The findings are based on a case study of an urban development district with a mandatory TPL-operated CLS, and we apply the industrial network approach. In this multi-project context, the main contractors engage in coopetitive relationships, coordinating activities and resources within and across projects. The TPL provider coordinates actors, resources, and activities, facilitating smoother production by managing logistics and mediating coopetitive relationships. This can be understood as a multi-project coordination role and extends the role SCM can play in construction. In that role, a TPL provider can minimise tensions between coopetitive actors across a multitude of horizontal relationships and projects.
|
|
| 7. |
- Eriksson, Helen, et al.
(författare)
-
Requirements, Development, and Evaluation of A National Building Standard-A Swedish Case Study
- 2020
-
Ingår i: ISPRS International Journal of Geo-Information. - : MDPI. - 2220-9964. ; 9:2
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to present a proposal for a national building standard in Sweden. We define requirements for the proposed standard, e.g., it should support development of 3D city models, connect to building information models (BIM) and national registers and be based on a national classification system for the urban environment. Based on these requirements we develop an Application Domain Extension (ADE) of the building model in the proposed CityGML 3.0 standard denoted CityGML Sve-Test. CityGML 3.0 includes several new features of interest, e.g., the space concept, enhanced possibilities to convert data, and to link to other standards. In our study we create test data according to CityGML Sve-Test and evaluate it against the requirements. It is shown that BIM models (in Industry Foundation Classes, IFC, format) can be converted to CityGML Sve-Test and that a classification system facilitates this conversion. The CityGML Sve-Test dataset can be used to increase the automation level in building permissions checking and a related study shows that CityGML 3.0 has capabilities to link to legal information and be a base for 3D cadastral index maps. Based on our experience, we suggest that the national building standard should conform to international standards and, if possible, include a classification system. The exchange format (GML, JSON etc.) might change, but to be based on a standardized data model ensures harmonized structures and concepts.
|
|
| 8. |
- Eriksson, Mimmi, et al.
(författare)
-
Effects of Gas Layer Thickness on Capillary Interactions at Superhydrophobic Surfaces
- 2024
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 40:9, s. 4801-4810
-
Tidskriftsartikel (refereegranskat)abstract
- Strongly attractive forces act between superhydrophobic surfaces across water due to the formation of a bridging gas capillary. Upon separation, the attraction can range up to tens of micrometers as the gas capillary grows, while gas molecules accumulate in the capillary. We argue that most of these molecules come from the pre-existing gaseous layer found at and within the superhydrophobic coating. In this study, we investigate how the capillary size and the resulting capillary forces are affected by the thickness of the gaseous layer. To this end, we prepared superhydrophobic coatings with different thicknesses by utilizing different numbers of coating cycles of a liquid flame spraying technique. Laser scanning confocal microscopy confirmed an increase in gas layer thickness with an increasing number of coating cycles. Force measurements between such coatings and a hydrophobic colloidal probe revealed attractive forces caused by bridging gas capillaries, and both the capillary size and the range of attraction increased with increasing thickness of the pre-existing gas layer. Hence, our data suggest that the amount of available gas at and in the superhydrophobic coating determines the force range and capillary growth.
|
|
| 9. |
- Eriksson, Mimmi, et al.
(författare)
-
Effects of liquid surface tension on gas capillaries and capillary forces at superamphiphobic surfaces
- 2023
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- The formation of a bridging gas capillary between superhydrophobic surfaces in water gives rise to strongly attractive interactions ranging up to several micrometers on separation. However, most liquids used in materials research are oil-based or contain surfactants. Superamphiphobic surfaces repel both water and low-surface-tension liquids. To control the interactions between a superamphiphobic surface and a particle, it needs to be resolved whether and how gas capillaries form in non-polar and low-surface-tension liquids. Such insight will aid advanced functional materials development. Here, we combine laser scanning confocal imaging and colloidal probe atomic force microscopy to elucidate the interaction between a superamphiphobic surface and a hydrophobic microparticle in three liquids with different surface tensions: water (73 mN m−1), ethylene glycol (48 mN m−1) and hexadecane (27 mN m−1). We show that bridging gas capillaries are formed in all three liquids. Force-distance curves between the superamphiphobic surface and the particle reveal strong attractive interactions, where the range and magnitude decrease with liquid surface tension. Comparison of free energy calculations based on the capillary menisci shapes and the force measurements suggest that under our dynamic measurements the gas pressure in the capillary is slightly below ambient.
|
|
| 10. |
- Eriksson, Mimmi, 1986-
(författare)
-
Super liquid-repellent surfaces - interactions and gas capillaries
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Super liquid-repellent surfaces have attracted a lot of interest in recent years. In addition to the large scientific interest there are many potential technological applications ranging from self-cleaning materials to microfluidic devices. In this thesis, interactions between liquid-repellent surfaces in liquids were studied, with the aim to investigate the detailed mechanisms of super liquid-repellence, such as superhydrophobicity and superamphiphobicity. An atomic force microscope (AFM) was used to measure the interaction forces between super liquid-repellent surfaces and a microsphere in different liquids. Additionally, a setup combining AFM with laser scanning confocal microscopy (LSCM) was used, which enabled simultaneous imaging in order to capture the microscopic events between the sphere and the surface during a force measurement. The confocal images successfully visualized how the strongly attractive forces measured between liquid-repellent surfaces are due to the formation of a gaseous capillary bridge between the two surfaces. Similar long-ranged forces with capillary formation and growth were observed both in water and in lower surface tension liquids. Additionally, the confocal images enabled determination of the capillary shape and volume, and the data showed an increase of the capillary volume during the major part of the process of separating the surfaces. A gaseous layer underneath the liquid at super liquid-repellent surfaces was also visualized with LSCM, and it was concluded that this gaseous layer is responsible for the formation and growth of large gas capillaries. It was found that an increased amount of available gas in the gaseous layer influenced the interactions and allowed the capillary to grow larger during separation. Further, theoretical calculations based on the size and shape of the capillary suggested that a small under pressure in the capillary drives the gas to flow from the gaseous surface layer into the capillary, facilitating growth during separation.
|
|
