| 1. |
- Alijagic, Andi, 1992-, et al.
(författare)
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Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
- 2022
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
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| 2. |
- Andersson, Annica, 1983, et al.
(författare)
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Roles of activating functions 1 and 2 of estrogen receptor α in lymphopoiesis.
- 2018
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Ingår i: The Journal of endocrinology. - 1479-6805. ; 236:2
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Tidskriftsartikel (refereegranskat)abstract
- Apart from the role of sex steroids in reproduction, sex steroids are also important regulators of the immune system. 17β-estradiol (E2) represses T and B cell development, but augments B cell function, possibly explaining the different nature of immune responses in men and women. Both E2 and selective estrogen receptors modulators (SERM) act via estrogen receptors (ER). Activating functions (AF)-1 and 2 of the ER bind to coregulators and thus influence target gene transcription and subsequent cellular response to ER activation. The importance of ERαAF-1 and AF-2 in the immunomodulatory effects of E2/SERM has previously not been reported. Thus, detailed studies of T and B lymphopoiesis were performed in ovariectomized E2-, lasofoxifene- or raloxifene-treated mice lacking either AF-1 or AF-2 domains of ERα, and their wild-type littermate controls. Immune cell phenotypes were analyzed with flow cytometry. All E2 and SERM-mediated inhibitory effects on thymus cellularity and thymic T cell development were clearly dependent on both ERαAFs. Interestingly, divergent roles of ERαAF-1 and ERαAF-2 in E2 and SERM-mediated modulation of bone marrow B lymphopoiesis were found. In contrast to E2, effects of lasofoxifene on early B cells did not require functional ERαAF-2, while ERαAF-1 was indispensable. Raloxifene reduced early B cells partly independent of both ERαAF-1 and ERαAF-2. Results from this study increase the understanding of the impact of ER modulation on the immune system, which can be useful in the clarification of the molecular actions of SERMs and in the development of new SERM.
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| 3. |
- Andersson, Helen, 1965
(författare)
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Chemical Rock Grouting. An Experimental Study on Polyurethane Foams
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Grouting is used to change the physical characteristics of concrete, soil and rock. The changes are usually related to permeability and/or strength. Although the most widely used grout for sealing of rock masses is cement suspension, there are certain conditions where polyurethane grout is used as a complement. The most favourable property in this respect is that such grouts react with water and expand due to exertion of carbon dioxide gas (CO2). Other important features of these grouts are the time dependency, the flow behaviour of unreacted as well as reacting polyurethane, and the physical influence of the carbon dioxide. The scope of this research was to study the typical behaviour of polyurethane grouts in order to explain why the grouting result has been unsatisfactory at times, while mostly successful where other grouts have failed. A comprehensive laboratory test programme was performed, including simple expansion tests, where the general characteristics of polyurethane grouts were studied, as well as a series of pipe flow tests. The latter tests comprised grouting of polyurethane against static groundwater pressure and into flowing water. The performance of polyurethane grouting in a field situation was also investigated with a test at the Röda Sten Rock Laboratory in Göteborg. The study resulted in conclusions and recommendations for the application of polyurethane for rock grouting. The main conclusion regarding the practical use of such grouts is that a volume criterion, in combination with an awareness of the time dependency of the gelling of the material, is useful for achieving an optimal sealing result. When grouting into flowing groundwater, a sufficiently high grouting pressure should be used in order to cut off the water flow and facilitate grout penetration upstream. The CO2 gas generated in the reaction between polyurethane and water, contributes to the grout penetration in two ways: (i) by causing a volume expansion, and (ii) by increasing the pressure behind the front of the reacting polyurethane grout.
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| 4. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 5. |
- Grundström, Christina, 1965-
(författare)
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Gaining influence in standard-setting processes : a discussion of underlying mechanisms in 3G mobile telephony technology development
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The environment in which companies operate is such that standards become increasingly important due to the built-in rigidities resulting from previous technology investments and network externalities. The research question is: How can a market-leading company gain influence on the formation of standards perceived as vital for the company-s continued business? The purpose of the dissertation is to explore, describe, and characterise how such influence may be gained; it thus aims to reveal some of the mechanisms underlying a technology standard-setting process. Market-leading here is interpreted as the company wanting to lead the development of the market by influencing the standards that will prevail in it, thereby aiming to secure market leadership (in measurable terms).The dominant design concept, including technical, commercial, and procedural dimensions, serves as the basis for the theoretical discussion. From the review of literature it is concluded that the dominant design concept marginally addresses the emergence of a dominant design. Therefore the present study takes on a company "inside-out" perspective to examine how underlying mechanisms may be revealed.The empirical data address the third generation (3G) mobile telephony core and access networks or the 3G infrastructure, which can be treated as the core technologies for the new 3G system. The data stem mainly from interviews with individuals involved in the process at Ericsson, the mobile telephony systems developer. One outcome of the research is a case that describes the story of 3G infrastructure standard setting from Ericsson's view.On the basis of empirical data and theoretical framework, four foci are developed and used for analysis of the data. The foci developed are people and their relations, organizations and their relations, technology perception, and influencing others.The point of departure is that the technology dimension is of utmost importance in this type of standard-setting process where a system of core technologies is chosen. After exploring and describing the process from the inside-out perspective, however, the overall finding from the research is that human behaviour plays the central role as individuals constitute the process by advocating and negotiating technology, form the organizations, embody the relations (including various types of network), and influence others in the market. Since people are at the core of standard-setting processes, a truly managerial issue is how to use the right people for the right tasks with proper timing during the process.The findings from the 3G study are also related to the findings made in earlier research in a broader contextual analysis.Critical to managing the standard-setting process is an understanding of where to fit a given standard into the technical hierarchy and the standards hierarchy. The maturity of the industry also needs to be analysed and addressed. It is concluded that each standard-setting process is a mix of de jure and de facto standard-setting mechanisms with "in-between arenas" and that there are a number of sub-processes.A model characterising the roles of people with various functions over time and in a standard-setting process constitutes the main outcome of the research. This model constitutes three different functions (technical, tactical, strategic) and three process stages (research, formal standardisation, informal standardisation) thereby characterising nine different roles.
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| 6. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified.
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 111:3, s. 1180-1185
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Tidskriftsartikel (refereegranskat)abstract
- The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-2(0)) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-2(0) mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-2(0) mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist.
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| 7. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Phosphorylation site S122 in estrogen receptor α has a tissue-dependent role in female mice
- 2020
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Ingår i: FASEB Journal. - 0892-6638 .- 1530-6860. ; 34, s. 15991-16002
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen treatment increases bone mass and reduces fat mass but is associated with adverse effects in postmenopausal women. Knowledge regarding tissue-specific estrogen signaling is important to aid the development of new tissue-specific treatments. We hypothesized that the posttranslational modification phosphorylation in estrogen receptor alpha (ERα) may modulate ERα activity in a tissue-dependent manner. Phosphorylation of site S122 in ERα has been shown in vitro to affect ERα activity, but the tissue-specific role in vivo is unknown. We herein developed and phenotyped a novel mouse model with a point mutation at the phosphorylation site 122 in ERα (S122A). Female S122A mice had increased fat mass and serum insulin levels but unchanged serum sex steroid levels, uterus weight, bone mass, thymus weight, and lymphocyte maturation compared to WT mice. In conclusion, phosphorylation site S122 in ERα has a tissue-dependent role with an impact specifically on fat mass in female mice. This study is the first to demonstrate in vivo that a phosphorylation site in a transactivation domain in a nuclear steroid receptor modulates the receptor activity in a tissue-dependent manner.
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| 8. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Probiotics protect mice from ovariectomy-induced cortical bone loss.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.
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| 9. |
- Thorgeirsdottir, Lilja, et al.
(författare)
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Study protocol: establishment of a multicentre pre-eclampsia database and biobank in Sweden: GO PROVE and UP MOST, a prospective cohort study
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women’s and their partners’ experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care.Methods and analysis This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women’s and partner’s experiences are distributed at follow-up.Ethics and dissemination By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women’s personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).
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