| 1. |
- Lizon, Jean Louis, et al.
(author)
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Opto-mechanical design of a new Cross Dispersion Unit for the CRIRES plus high resolution spectrograph for the VLT
- 2014
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
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Conference paper (peer-reviewed)abstract
- CRIRES is one of the few IR (0.92-5.2 mu m) high-resolution spectrographs in operation at the VLT since 2006. Despite good performance it suffers a limitation that significantly hampers its ability: a small spectral coverage per exposure. The CRIRES upgrade (CRIRES+) proposes to transform CRIRES into a cross-dispersed spectrograph while maintaining the high resolution (100000) and increasing the wavelength coverage by a factor 10 compared to the current capabilities. A major part of the upgrade is the exchange of the actual cryogenic pre-disperser module by a new cross disperser unit. In addition to a completely new optical design, a number of important changes are required on key components and functions like the slit unit and detectors units. We will outline the design of these new units fitting inside a predefined and restricted space. The mechanical design of the new functions including a description and analysis will be presented. Finally we will present the strategy for the implementation of the changes.
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| 2. |
- Lizunkova, Polina, et al.
(author)
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Additivity provides a good approximation for the effect of a complex, human-relevant chemical mixture on metabolic outcomes
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Other publication (other academic/artistic)abstract
- Humans and the environment are exposed to complex mixtures of numerous synthetic chemicals. This study investigated whether the additivity model could predict effects of a human-relevant complex chemical mixture. The additivity model analysis was conducted on toxicological data from two experimental models exposed to the mixture and its individual compounds. The chemical mixture was previously identified in an epidemiological study to be associated with lower birth weight. This mixture consisted of 14 fourteen chemicals from different classes. Gompertz nonlinear function was used for individual compound and mixture analysis. We showed that the additivity model provided an adequate and larger estimate for mixture effects for both experimental assays in comparison to the measured effects, despite for one of the assays the test for additivity was rejected. Our results underscore dose addition model applicability for regulatory risk assessment of complex human-relevant chemical mixtures.
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| 3. |
- Nilsson, Erik, 1983-, et al.
(author)
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Convective boundary-layer structure in the presence of wind-following swell
- 2012
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In: Quarterly Journal of the Royal Meteorological Society. - : Wiley. - 0035-9009 .- 1477-870X. ; 138:667, s. 1476-1489
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Journal article (peer-reviewed)abstract
- The marine boundary layer is known to be influenced by fast long ocean swell waves travelling away from their generation area, where they were initiated by momentum transferred to the ocean wave field during storms. The atmospheric boundary layer during wind-following swell and various stability states has been investigated using large-eddy simulation (LES) data. The dominant energy-containing motions in the near-neutral atmospheric boundary layer over flat terrain are known to be dominated by near-ground shear-induced regions of high- and low-speed flow. Windfields and momentum fluxes from LES for swell-dominated situations have been used to interpret field measurements suggesting that these motions are disrupted by effects related to the underlying wave field in the presence of swell waves. Statistical analysis and visualization are used to further describe the effects of stratification during swell for convective boundary-layer winds and fluxes. A mechanism for transport of momentum to the upper levels of the boundary layer is suggested from interpretation of LES data. Coherent detached eddies from the directly wave-induced motions near the surface are found to maintain an upward momentum transfer. This mechanism is found to strengthen during stronger swell conditions and also during slightly convective conditions. In this way, it is argued that processes related to both the wave field and surface convection can have a significant influence on the global structure of neutral and convective boundary layers during swell. This has implication for the turbulence length-scales during wind-following swell.
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| 4. |
- Nilsson, Emeli
(author)
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Fibroblast growth factor-8 regulation of breast cancer cell growth
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Expression of fibroblast growth factor-8 (FGF-8) is increased in a large number of breast cancers. In in vitro and in vivo breast cancer models FGF-8 promotes growth, invasion and angiogenesis. In the present work we have studied the mechanisms by which FGF-8b and its receptors (FGFR1-3) promote breast cancer cell growth using S115 murine and human MCF-7 breast cancer cell lines in in vitro and in vivo models. We have also examined FGF-8 protein level together with FGFR2, and the androgen receptor by means of immunohistochemical staining of tumour tissues from 144 women diagnosed with invasive breast cancer. We found that FGF-8b induces cell cycle progression and proliferation by upregulating cyclin D1 via the MAPK/ERK, PI3K/Akt and p38/MAPK pathways in breast cancer cells. Moreover, we found that FGF-8b promotes growth and survival of breast cancer cells by protecting against cell death. FGF-8b-regulated breast cancer cell growth was further characterised by gene expression profiling of breast cancer cells treated with FGF-8b, from 1 to 24 hours. The most up- or downregulated genes in response to FGF-8b treatment mainly belonged to the functional categories and pathways related to mitosis, cell cycle regulation, cancer, and cell death. A number of key regulatory genes of cell cycle and mitosis including Btg2, Plk1 and aurora A were identified as novel targets for FGF-8b. The role of FGF receptors 1-3 in breast cancer cell growth was studied in three different cell lines silenced for expression of FGFR1, 2 and 3, respectively. Studies on growth and signalling of the FGFR1-3 silenced cell lines in vitro as well as in nude mouse tumours revealed differential roles of FGFR1 and FGFR2 in this breast cancer cell model. While FGFR1 strongly promoted growth, FGFR2 seemed to have tumour suppressing functions. In human breast cancer specimens FGF-8 and FGFR2 protein expression was shown to correlate negatively with each other. We also found downregulation of FGFR2 protein expression by FGF-8b in vitro in breast cancer cells. In accordance with these results, FGFR2 expression correlated negatively with tumour size. These results further suggest a tumour suppressor function for FGFR2. In conclusion, FGF-8 and its receptors primarily regulate breast cancer cell proliferation and survival. The novel targets and mechanisms identified may be of importance in developing therapies against breast cancer.
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| 5. |
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| 6. |
- Svingstedt, Anette, et al.
(author)
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When lock-ins impede value co-creation in service
- 2018
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In: International Journal of Quality and Service Sciences. - 1756-669X. ; 10:1, s. 2-15
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Journal article (peer-reviewed)abstract
- Purpose: This paper aims to demonstrate the relevance of identifying lock-ins that characterise a service, showing how lock-ins or impediments reinforce the status quo and prevent change. It provides an understanding of the factors hindering the development of value co-creation in this service. Design/methodology/approach: The study is based on 19 semi-structured interviews with representatives of the Swedish waste management industry. It focusses on the difficulties that waste management companies encounter when they try to collaborate with their industrial customers to develop waste prevention services. Findings: Four lock-ins that impede collaborative ways of working are identified: a business model based on short-term transactions rather than long-term relationships, a low level of self-confidence among waste managers regarding their competence to offer waste prevention services, non-supportive legal and economic institutional factors and existing waste processing infrastructures. Research limitations/implications: Based on a case of waste services and to provide a better understanding of the rationale of value co-creation, this paper points to the generic relevance of investigating situations in which value co-creation encounters difficulties. Practical implications: The authors identify the fact that lock-ins impeding value co-creation can act as a roadmap for the development of new services. Originality/value: By focusing on a case of unsuccessful value co-creation, the paper offers a counterpoint to cases of successful value co-creation.
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| 7. |
- Svoboda, Peter, 1963-
(author)
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Mechanisms of formation and protection against oxidative DNA damage in vitro and in vivo
- 2001
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Doctoral thesis (other academic/artistic)abstract
- Oxidative DNA damage has been linked to cancer and aging as well as other diseases. The aim of this thesis was to study the mechanisms for DNA damage generated in cells or in vitro systems by ionizing radiation or transition metals like iron ions. The damage primarily studied, was 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG), formed by the attack of hydroxyl radical on DNA. Due to its incorrect base pairing with deoxyadenosine during cell replication, 8-oxo-dG is potentially mutagenic. This base damage was analysed with the method of high performance liquid chromatography and electrochemical detection. Also other endpoints of DNA damage were measured, such as the formation of DNA strand breaks with the alkali unwinding assay.Oxidation of iron ions was shown to be dependent on chelation to phosphate ions in solution as well as phosphate bound to DNA. Increasing the ratio of phosphate to ferrous iron (Fe2+) was correlated with the increased formation of 8-oxo-dG. Quin2, a metal chelator, was shown to redox cycle normally unreactive ferric iron (Fe3+) to its reduced form, Fe2+ in the presence of hydrogen peroxide, thereby producing hydroxyl radicals and damage such as 8-oxo-dG. Compounds with these properties would thus be considered as potentially mutagenic.In vitro, it was seen that the yield of 8-oxo-dG was severalfold higher upon irradiation of DNA as compared to irradiation of deoxyguanosine in solution, due to properties of the DNA structure itself. Adding scavengers to DNA, highest protection against damage could be seen using thiols with positive net charge, due to the formation of a counterion condensation complex with the negatively charged DNA, thus protecting more efficiantly against oxygen radical damage. The novel finding was that scavengers with reducing properties, like thiols or ascorbate, added to the nucleoside deoxyguanosine in solution, increased the radiation induced formation of 8-oxo-dG severalfold.Further, the protective effect of chromatin conformation was studied. The yield of radiation induced DNA damage increased when removing low molecular weight nuclear components upon permeabilisation of cells, demonstrating a larger role of hydroxyl radicals for the formation of 8-oxo-dG relative to DNA strand breaks. The removal of histones produced the highest levels of DNA damage, in the form of DNA strand breaks and 8-oxo-dG. In histone free DNA, thiol with positive net charge provided the best protection against formation of 8-oxo-dG.In vivo formation of 8-oxo-dG was studied in rats fed diets supplemented with iron and/or alcohol. In response to iron overload there was only a minor, insignificant, increase of 8-oxo-dG in rat liver cells, and a synergistic effect of iron and alcohol on cytotoxicity but with no genotoxicity.The excretion of 8-oxo-dG in urine was followed in response to radiotherapy of patients treated for breast cancer. The levels of 8-oxo-dG in the urine, before and in response to radiotherapy, correlated with the patients radiosensitivity. Thus, patients with higher radiosensitivity were considered to have a lower repair capacity for this damage.
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