| 1. |
- Gusev, A, et al.
(författare)
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
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Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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| 2. |
- Edner, H, et al.
(författare)
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Atmospheric Mercury Mapping In A Cinnabar Mining Area
- 1993
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Ingår i: Science of the Total Environment. - 1879-1026. ; 133:1-2, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- A mobile differential absorption lidar system was used in conjunction with point monitors to study the spatial and temporal distribution of atomic mercury in the atmosphere around an abandoned mercury mine at Abbadia S. Salvatore, Italy. The use of the remote sensing technique allows a fast coverage of large areas both horizontally and vertically with a good temporal resolution. Concentrations exceeding 1000 ng/m3 were measured close to the distillation plant and considerably elevated values also were evident above deposits of roasted cinnabar. Vertical gradients of the mercury concentration in air were established. These showed a very pronounced decrease a few centimeters above the ground.
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| 3. |
- Edner, H, et al.
(författare)
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Differential Absorption Lidar Mapping of Atmospheric Atomic Mercury In Italian Geothermal Fields
- 1992
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Ingår i: Journal of Geophysical Research. - 2156-2202. ; 97:D4, s. 3779-3786
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Tidskriftsartikel (refereegranskat)abstract
- Results from extensive lidar measurements on atmospheric atomic mercury in Italian geothermal fields are reported. A mobile differential absorption lidar system operating on the 254-nm mercury resonance line with a measuring range of about 1 km was used in mineralized as well as nonmineralized areas. Measurements were performed at geothermal power stations and in an unexploited field with natural surface geothermic manifestations. Atomic mercury concentrations ranging from 2 to 1000 ng/m3 were mapped. The high Italian geothermal mercury concentrations are in strong contrast to the recent lidar finding of the absence of atomic mercury in Icelandic geothermal fields.
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| 4. |
- Ferrara, R, et al.
(författare)
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Atmospheric Mercury Emission At Solfatara Volcano (Pozzuoli, Phlegraean Fields, Italy)
- 1994
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Ingår i: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 29:7, s. 1421-1428
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Tidskriftsartikel (refereegranskat)abstract
- Mercury concentrations in air and in condensed steam coming from fumarolic activity at the Solfatara crater (Phlegraean Fields - Italy) were determined. In the condensed steam, mercury was found mainly associated as Hg-S complexes and showed a flux in the range from 0.9 to 4.5 g day(-1). Using the point monitor technique, high values (up to 690 ng m(-3)) of atmospheric mercury levels were observed only close to the main exhaling areas, while background levels (2 ng m(-3)) were measured over the crater area using the lidar technique. An upper limit (<2.4 g day(-1)) for the flux of elemental mercury in air was estimated with the lidar. This remote sensing technique also allowed to assess an upper limit for the SO2 flux (<24 kg day (-1)).
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| 5. |
- Ferrara, R, et al.
(författare)
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Mercury Emissions Into the Atmosphere From A Chlor-alkali Complex Measured With the Lidar Technique
- 1992
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Ingår i: Atmospheric Environment Part A-general Topics. - 0004-6981. ; 26:7, s. 1253-1258
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Tidskriftsartikel (refereegranskat)abstract
- Data are reported on atmospheric mercury flux measured by a lidar system at a chlor-alkali plant located in central Italy. Two mercury sources were identified over the electrolytic cell rooms. A flux value of 36 g h-1 was determined during the daytime while at night the value increase to 56 g h-1. The mercury emitted into the atmosphere was found to be 4 g per 1000 kg of chlorine produced. Atmospheric mercury concentrations were supplemented with some determinations made with the point monitor technique.
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| 6. |
- Ferrara, R, et al.
(författare)
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Vertical Profiles of Atmospheric Mercury Concentration
- 1992
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Ingår i: Environmental Technology. - : Informa UK Limited. - 1479-487X .- 0959-3330. ; 13:11, s. 1061-1068
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Tidskriftsartikel (refereegranskat)abstract
- Vertical profiles of atmospheric mercury concentration determined with a lidar and point monitor systems in the mineralized region of Mt. Amiata (Italy) are reported. Measurements were performed over a large flat area, without arboreal and herbaceous vegetation, constituting a roasted cinnabar deposit which still contains about two parts per thousand of mercury. The determinations carried out with the two techniques yielded comparable results for the working conditions used. Data demonstrate the presence of a vertical gradient of atmospheric mercury concentration, which is particularly large in the layers of air nearest the soil. The highest values (45-1000 ng m-3) were measured a few centimeters from the soil, while background values (2-3 ng m-3) were reached at heights of 10-20 m. The vertical gradient proved to be strongly dependent on ambient temperature.
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| 7. |
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| 8. |
- Bertling, Sofia, 1970-
(författare)
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Corrosion-included metal runoff from external constructions and its environmental interaction : a combined field and laboratory investigation of Zn, Cu, Cr and Ni for risk assessment
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The 1990s has seen an increased awareness of possible environmental effects of corrosion-induced metal release from outdoor constructions. Considerable efforts have been initiated to perform critical assessments of possible risks of selected metals. Gaps of knowledge have been identified and research investigations started. This doctoral thesis is the result of an interdisciplinary research effort in which scientific insight into corrosion, soil chemistry and ecotoxicology has been integrated. The work comprises atmospheric exposure of pure metals and commercial materials for outdoor use. The focus is on release of four metals, copper, zinc, chromium and nickel. Their chemical speciation and bioavailable fraction in metal runoff were determined, both at the release moment and after environmental interaction with, e.g., soil and limestone. Total metal concentrations in runoff are influenced both by material properties (e.g., corrosion product solubility, and specific surface area) and by exposure parameters (e.g., rain volume, intensity, contact time and pollutants). Long-term runoff rates of copper, zinc, chromium and nickel were based on exposures (4-8 years) at standardized conditions (45o inclination facing south) in Stockholm, Sweden. Runoff rates for pure copper range from 1.2 to 1.5 g m-2 yr-1, depending on year. At the copper release moment the potential environmental effect was evaluated using 72 hours growth inhibition test with the green algae Raphidocelis subcapitata. This resulted in a mean value of 15 μg L-1 causing a 50% growth reduction (EC50). Long-term runoff rates for pure zinc range from 1.9 to 2.5 g m-2 yr-1. A considerable variation in average annual runoff rates (0.07-2.5 mg zinc m2yr-1) was observed between different investigated commercial zinc-based materials. An average 72 hour (EC50) value of 69 μg L-1 towards Raphidocelis subcapitata was found for runoff water from zinc-based materials. Long-term runoff rates from stainless steel of grade 304 and 316 range from 0.23 to 0.30 chromium and 0.28 to 0.52 nickel mg m-2 yr-1, with corresponding concentrations in the runoff at the release moment far below reported ecotoxic concentrations for chromium and nickel. Two predictive runoff rate models were successfully developed for transforming copper runoff rate data from Stockholm to other exposure sites. One model is based on rain pH, yearly precipitation and building geometry, and the other on average annual SO2 concentration, yearly precipitation and building geometry. In addition to total metal concentration, adequate effect assessments also require information on chemical speciation of the released metal and its bioavailability. Metal chemical speciation in runoff was determined experimentally through an ion selective electrode (for copper), and also modelled with the Windermere Humic Aquatic model (WHAM (V)). Bioavailability assessments were generated through bioassay tests. At the moment of metal release, all methods show that the majority (60-99%) of the metal in runoff exists in its most bioavailable form, the hydrated metal ion. During subsequent environmental entry the metal undergoes major reductions in concentration and bioavailability. This was evidenced by model column studies of the capacity of soil to retain and immobilize the metal in runoff water, and by model and field column studies of the capacity of limestone to retain copper. The retention by soil of all metals investigated is very high (96-99.8%) until each materials retention capacity is reached. Limestone also exhibits a substantial capacity (5- 47%) to retain copper. The capacity is significantly increased by increased amount and decreased fraction of limestone particles. Any outer or inner surface with significant retention ability and with low possibility of subsequent mobilization is an excellent candidate for neutralizing metal release and its potential ecotoxic effects. This was demonstrated through computer modelling (WHAM(V)) and biosensor tests (Biomet™), which showed the most bioavailable and ecotoxic metal species to be reduced during passage through soil and limestone. Predictions based on the computer model HYDRUS-1D suggest a time-period of between 4 and 8000 years, depending on runoff water and soil characteristics, before saturation in soil retention capacity of copper and zinc is reached. A significant fraction of the retained metal is extractable towards the strong complexing agent EDTA, indicating possible future mobilisation. It is also available for plant uptake, as shown by DGT- (Diffuse Gradients in Thin films-) analysis of copper and zinc in soil. The data generated, presented and discussed are all believed to be important for risk assessment work related to corrosion-induced metal release from outdoor constructions. As evidenced from this doctoral thesis, such work requires a complete set of data on annual runoff rates, concentrations, chemical speciation and bioavailability and its changes during environmental entry, together with knowledge on, e.g., type of material, service life of coating, building geometry, and dewatering system.
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| 9. |
- Bertling, Sofia, et al.
(författare)
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Model studies of corrosion induced copper runoff fate in soil
- 2006
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Ingår i: Environmental Toxicology and Chemistry. - 0730-7268 .- 1552-8618. ; 25:3, s. 683-691
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory experiments have been performed with 3-cm soil columns simulating the fate of corrosion-induced copper runoff in contact with soil. The investigation simulates approximately 30 years (assuming an infiltration surplus of 25 cm/year) of continuous percolation of copper containing runoff water of a concentration realistic at the immediate release situation (4.8 mg/L) into four soils representative of urban conditions. Two of the three investigated topsoils reached their breakthrough of copper within the simulated time, while the third topsoil did not show a breakthrough. The subsoil reached a breakthrough after approximately 10 years of simulated exposure. To simulate more realistic outdoor scenarios, the laboratory-obtained breakthrough curves were modeled with Hydrus-1D (R) using a Langmuir-Freundlich model to describe copper sorption, the parameters of which were estimated from soil properties (pH, organic carbon content). The model predicts longer breakthrough times with increasing pH and organic content of the soil and with decreasing concentrations of copper and dissolved organic carbon in the runoff water. The time span for copper in runoff water (at concentrations of 0.01-10 mg/L) to reach a soil depth of 50 cm varied between 170 and more than 8,000 years for the predicted field scenarios.
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| 10. |
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| 11. |
- Edner, H, et al.
(författare)
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Fluorescence Lidar Multicolor Imaging of Vegetation
- 1994
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Ingår i: Optical Society of America. Journal B: Optical Physics. - 0740-3224. ; 33:13, s. 2471-2479
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Tidskriftsartikel (refereegranskat)abstract
- Multicolor imaging of vegetation fluorescence following laser excitation is reported for distances of 50 m. A mobile laser-radar system equipped with a Nd:YAG laser transmitter and a 40-cm-diameter telescope was utilized. The laser light was Raman shifted to 397 nm with pulse energies of approximately 30 mJ. An image-intensified CCD camera with a specially designed split-mirror Cassegrainian telescope was utilized for the simultaneous recording of fluorescence images of leaves and branches in four different spectral bands. Additionally, fluorescence spectra at selected points within the detection area were measured with an image-intensified diode array system. Image processing permits extraction of information related to the physiological status of the vegetation and might prove useful in forest decline research.
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| 12. |
- Edner, Hans, et al.
(författare)
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Industrial Emission Control Using Lidar Techniques
- 1995
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 29:2, s. 330-337
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Tidskriftsartikel (refereegranskat)abstract
- A mobile DIAL (differential absorption lidar) remote sensing system has been employed in the monitoring of industrial pollutant emissions. Measurements of sulfur dioxide and mercury vapor were performed at nine different Swedish industrial plants within the framework of a control program commissioned by the Swedish Environmental Protection Agency. Total atmospheric fluxes of these species could be determined by combining wind data with a mapping of the concentration distribution downwind from the sources. The emission values obtained were compared with in situ measurements made by the companies themselves. The values from single point sources correlate well, whereas the DIAL system normally measures a higher total flux from several distributed sources including diffuse emissions. The results are used to discuss the applicability and limitation of the DIAL technique for remote surveillance of industrial emissions.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Ferrara, R, et al.
(författare)
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Atmospheric mercury sources in the Mt. Amiata area, Italy
- 1998
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Ingår i: Science of the Total Environment. - 1879-1026. ; 213:1-3, s. 13-23
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Tidskriftsartikel (refereegranskat)abstract
- Mt. Amiata, located in southern Tuscany (Italy), is part of the geologic anomaly of the Mediterranean basin, which contains about 65% of the world's cinnabar (HgS) deposits. Atmospheric mercury emissions from the main sources (geothermal power plants, abandoned mine structures and spoil banks of roasted cinnabar ore) were determined by flux chamber and by LIDAR remote sensing. Mercury emissions from five geothermal power plants were on the order of 24 g h(-1) for each plant, a value that remains constant throughout the year. In the month of July, the mine spoils (covering an area of similar to 200000 m(2)) emit a few grams of mercury per hour, while the abandoned mine structures give off 100-110 g h(-1). These two mercury sources were strongly influenced by ambient temperature. The area affected by mercury sources displays an average air mercury concentration of 20 ng m(-3) during the summer and 10 ng m(-3) in winter. (C) 1998 Elsevier Science B.V.
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| 17. |
- Ferraris, M., et al.
(författare)
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Antibacterial silver nanocluster/silica composite coatings on stainless steel
- 2017
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Ingår i: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 396, s. 1546-1555
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Tidskriftsartikel (refereegranskat)abstract
- A coating made of silver nanocluster/silica composites has been deposited, via a radio frequency (RF) co-sputtering technique, for the first time onto stainless steel (AISI 304L) with the aim to improve its antibacterial properties. Different thermal treatments after coating deposition have been applied in order to optimize the coating adhesion, cohesion and its antibacterial properties. Its applicability has been investigated at realistic conditions in a cheese production plant. The physico-chemical characteristics of the coatings have been analyzed by means of different bulk and surface analytical techniques. Field emission scanning electron microscopy (FESEM), X-ray Photoelectron Spectroscopy (XPS), contact angle measurements and atomic force microscopy (AFM) were employed to assess coating morphology, composition, surface roughness, wetting properties, size and local distribution of the nanoparticles within the coating. Tape tests were used to determine the adhesion/cohesion properties of the coating. The amount and time-dependence of released silver in solutions of acetic acid, artificial water, artificial tap water and artificial milk were determined by means of Atomic Absorption Spectroscopy (AAS). The antibacterial effect of the coating was evaluated at different experimental conditions using a standard bacterial strain of Staphylococcus aureus in compliance with National Committee for Clinical Laboratory Standards (NCCLS) and AATCC 147 standards. The Ahearn test was performed to measure the adhesion of bacteria to the coated stainless steel surface compared with a control surface. The antibacterial coating retained its antibacterial activity after thermal treatment up to 450 °C and after soaking in common cleaning products for stainless steel surfaces used for e.g. food applications. The antibacterial capacity of the coating remained at high levels for 1-5 days, and showed a good capacity to reduce the adhesion of bacteria up to 30 days. Only a few percent of silver in the coating was released into acetic acid, even after 10 days of exposure at 40 °C. Most silver (> 90%) remained also in the coating even after 240 h of continuous exposure. Similar observations were made after repeated exposure at 100 °C. Very low levels of released silver in solution were observed in artificial milk. No release of silver nanoparticles was observed either in synthetic tap water or in artificial milk at given conditions. The coating further displayed good antibacterial properties also when tested during working conditions in a cheese production plant.
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| 18. |
- Ferraris, Sara, et al.
(författare)
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Chemical, mechanical and antibacterial properties of silver nanocluster/silica composite coated textiles for safety systems and aerospace applications
- 2014
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 317, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- This work describes the chemical, mechanical and antibacterial properties of a novel silver nanocluster/silica composite coating, obtained by sputtering, on textiles for use in nuclear bacteriological and chemical (NBC) protection suites and for aerospace applications.The properties of the coated textiles were analyzed in terms of surface morphology, silver concentration and silver release in artificial sweat and synthetic tap water, respectively. No release of silver nanoparticles was observed at given conditions.The water repellency, permeability, flammability and mechanical resistance of the textiles before and after sputtering demonstrated that the textile properties were not negatively affected by the coating.The antibacterial effect was evaluated at different experimental conditions using a standard bacterial strain of Staphylococcus aureus and compared with the behavior of uncoated textiles.The coating process conferred all textiles a good antibacterial activity. Optimal deposition conditions were elaborated to obtain sufficient antibacterial action without altering the aesthetical appearance of the textiles.The antibacterial coating retained its antibacterial activity after one cycle in a washing machine only for the Nylon based textile.
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| 19. |
- Hedberg, Yolanda, Docent, 1985-, et al.
(författare)
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Welding fume nanoparticles from solid and flux-cored wires : Solubility, toxicity, and role of fluorides
- 2021
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Ingår i: Journal of Hazardous Materials. - : Elsevier BV. - 0304-3894 .- 1873-3336. ; 413
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Tidskriftsartikel (refereegranskat)abstract
- Welding fume particles are hazardous. Their toxicity likely depends on their composition and reactivity. This study aimed at exploring the role of sodium or other fluorides (NaF), which are intentionally added to flux-cored wire electrodes for stainless steel welding, on the solubility (in phosphate buffered saline) and toxicity of the generated welding fume particles. A multi-analytical particle characterization approach along with in-vitro cell assays was undertaken. The release of Cr(VI) and Mn from the particles was tested as a function of fluoride solution concentration. The welding fume particles containing NaF released significantly higher amounts of Cr (VI) compared with solid wire reference fumes, which was associated with increased cytotoxicity and genotoxicity in-vitro. No crystalline Na or potassium (K) containing chromates were observed. Cr(VI) was incorporated in an amorphous mixed oxide. Solution-added fluorides did not increase the solubility of Cr(VI), but contributed to a reduced Mn release from both solid and flux-cored wire fume particles and the reduction of Cr (VI) release from solid wire fume particles. Chemical speciation modeling suggested that metal fluoride complexes were not formed. The presence of NaF in the welding electrodes did not have any direct, but possibly an indirect, role in the Cr(VI) solubility of welding fumes.
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| 20. |
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| 21. |
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| 22. |
- Lindqvist, Markus, et al.
(författare)
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Plasma glycosylphosphatidylinositol phospholipase D (GPI-PLD) and abdominal aortic aneurysm.
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:4, s. 306-9
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Tidskriftsartikel (refereegranskat)abstract
- Recent reviews state that a circulating biomarker predicting aortic rupture risk would be a powerful tool to stratify patients with small screen-detected abdominal aortic aneurysm (AAA). In a current proteomic pilot-study elevated levels of the enzyme Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) was shown in patients with small AAA compared with controls without aneurysm. In the present study we investigated the impact of plasma GPI-PLD as a biomarker in patients with AAA in relation to aneurysm size, and rupture. Plasma GPI-PLD was measured in patients with AAA (nonruptured, n=78 and ruptured, n=55) and controls without aneurysm (n=41) matched by age, sex and smoking habit. The plasma GPI-PLD levels were significantly lower in patients with ruptured compared nonruptured AAA which we interpreted as a result of hemodilution due to hemorrhage in patients with ruptured AAA. The plasma GPI-PLD levels were similar in patients with nonruptured AAA compared to the controls without aneurysm. Furthermore, there was no correlation between plasma GPI-PLD and aneurysm size in the group of patients with nonruptured AAA. In conclusion, the present study fails to show a connection between GPI-PLD and AAA. However, the definite role of GPI-PLD as a predictive marker needs to be further clarified in a follow-up cohort study.
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| 23. |
- Lindqvist, Markus, et al.
(författare)
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Soluble urokinase plasminogen activator receptor in patients with abdominal aortic aneurysm
- 2012
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:3, s. 511-513
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the present study we investigated the impact of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker in patients with abdominal aortic aneurysm (AAA) in relation to conventional inflammatory markers, aneurysm size, and rupture. Methods: suPAR and conventional inflammatory markers were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. Results: The results support earlier studies suggesting a state of activated inflammatory response in patients with nonruptured AAA as expressed by elevated CRP and IL-6 compared with the controls. In contrast, suPAR showed similar levels in patients with nonruptured AAA compared with the controls. Unexpectedly, all follow-up patients (n = 16) have significant (p<0.001) elevated suPAR levels three years postoperatively compared preoperatively. Conclusions: suPAR does not seem to be a useful biomarker in the AAA disease. The role of the postoperative elevation of suPAR needs to be further elucidated. (C) 2012 Elsevier Ltd. All rights reserved.
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| 24. |
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| 25. |
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| 26. |
- Steckelings, U. Muscha, et al.
(författare)
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Non-peptide AT2-receptor agonists
- 2011
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Ingår i: Current opinion in pharmacology (Print). - : Elsevier BV. - 1471-4892 .- 1471-4973. ; 11:2, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- The renin-angiotensin-system harbours two main receptor subtypes binding angiotensin II which are the AT1-receptor and the AT2-receptor. While the AT1-receptor has been a drug target in cardiovascular disease for many years, the AT2-receptor was only a subject of academic interest. This has changed with the design and synthesis of a first non-peptide, orally active AT2-receptor agonist, compound 21 (C21). First data using 021 revealed tissue protective effects and functional improvement after myocardial infarction and in hypertension-induced end organ damage, notably in a blood-pressure independent way. In all of these models, AT2-receptor mediated anti-inflammation seemed an important underlying mechanism. 021 is awaited to enter a phase I clinical study in 2011.
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| 27. |
- Viklander, Gertrud, et al.
(författare)
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ABO blood groups and abdominal aortic aneurysm.
- 2012
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Ingår i: Transfusion and apheresis science. - : Elsevier BV. - 1473-0502 .- 1878-1683. ; 47:3, s. 351-3
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Tidskriftsartikel (refereegranskat)abstract
- Earlier studies have indicated an association between blood group non-O and atherosclerosis related vascular diseases. Abdominal aortic aneurysm (AAA) is traditionally regarded as a consequence of atherosclerosis. The aim of the present study was to investigate the association between ABO blood groups and AAA with special regard to a relation to AAA rupture. Prospectively, 504 patients operated on for AAA were investigated. Patients operated on for AAA have similar ABO blood group distributions as a population based control group. Furthermore, there was no significant difference in distribution of ABO blood group between patients operated on for ruptured AAA (n=174) and non-ruptured AAA (n=330). In conclusion, this study fails to demonstrate an association between ABO blood groups and AAA.
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| 28. |
- Wallinder, Charlotta, 1976-
(författare)
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Design, Synthesis and Biological Evaluation of Selective Nonpeptide AT2 Receptor Agonists and Antagonists
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The G protein-coupled receptors (GPCRs) are important targets in drug discovery. In several cases, the endogenous ligands that activate the GPCRs of pharmaceutical interest are peptides. Unfortunately, peptides are in general not suitable as drugs, since the peptide structure is associated with several disadvantages, such as low oral bioavailability, rapid degradation and low receptor subtype selectivity. Thus, there is a strong need for drug-like nonpeptide ligands to peptide-activated GPCRs. However, to discover nonpeptide ligands that mimic the effect of the endogenous peptide, i.e. peptidomimetics, is a tremendous challenge. In fact, morphine and the related opioids were the only known examples of peptidomimetics before 1995 and these ligands were known long before the native endogenous peptide ligands were discovered. The main objective of the work described in this thesis was to design, synthesize and biologically evaluate selective nonpeptide agonists to the peptide-activated GPCR AT2. The AT2 receptor belongs to the renin–angiotensin system, where the octapeptide angiotensin II (Ang II) is the major effector peptide. Ang II mediates its effects through the two GPCRs AT1 and AT2. The AT1 receptor is already an established target in the treatment of hypertension. The physiological role of the AT2 receptor, which is up-regulated in certain pathological conditions, is not fully understood but it seems to include positive effects such as vasodilatation, tissue repair, tissue regeneration and neuronal differentiation. In the current investigation we started from the nonpeptide and nonselective (AT1/ AT2) compound L-162,313. This ligand is a known AT1 receptor agonist but its effect on the AT2 receptor was unknown at the start of this project. We were able to show that it acts as an agonist also at the AT2 receptor. Furthermore, stepwise synthetic modifications of L-162,313 led to the identification of the first selective nonpeptide AT2 receptor agonist. Following the discovery of this compound several selective nonpeptide AT2 receptor agonists were identified. It was also revealed that a minor structural alteration of one of these compounds interconverted the functional activity from agonism to antagonism. The structural requirement for agonism vs antagonism was therefore studied. The functionality switch was suggested, at least partly, to be due to the spatial relationship between the methyleneimidazole group and the isobutyl side chain of the compounds. To further investigate the bioactive conformation(s) of this series of compounds enantiomerically pure analogues with conformationally constrained isobutyl chains were prepared. This study revealed that the direction of the isobutyl side chain determine whether the compounds act as agonists or antagonists at the AT2 receptor. Further investigations are required to fully elucidate the bioactive conformation(s) of these nonpeptide AT2 receptor agonists.We believe that the selective nonpeptide AT2 receptor agonists and antagonists identified in this thesis will serve as important research tools in the continuing investigation of the physiological role of the AT2 receptor. We also believe that these drug-like compounds might provide potential leads in drug discovery processes.
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| 29. |
- Wallinder, D., et al.
(författare)
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Hydrogen in chromium : influence on corrosion potential and anodic dissolution in neutral NaCl solution
- 2001
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Ingår i: Corrosion Science. - 0010-938X .- 1879-0496. ; 43:7, s. 1267-1281
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Tidskriftsartikel (refereegranskat)abstract
- The influence of hydrogen charging, outgassing, pickling and passivation of mechanically polished chromium was investigated with respect to corrosion potential and anodic dissolution in 0.3 M NaCl solution. Secondary ion mass spectroscopy measurements were used to detect hydrogen after hydrogen charging by means of cathodic polarization. The results show that hydrogen in chromium decreases the corrosion potential and increases the anodic dissolution rate. Passivation in HNO3 and pickling in HNO3 + HF increases the corrosion potential, whereas no significant effect on the anodic dissolution could be observed, probably due to a hydrogen uptake in these surface treatments.
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| 30. |
- Wallinder, D., et al.
(författare)
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Influence of hydrogen in iron and in two stainless steels on aqueous and gaseous corrosion
- 2002
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 149:9, s. B393-B397
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Tidskriftsartikel (refereegranskat)abstract
- The influence of hydrogen in Fe, 301 stainless steel (SS 301), and Avesta 353MA on corrosion resistance in aqueous solutions was studied. The oxidation kinetics of uncoated and Pt-coated Fe was also investigated in O-2 at 500 and 700degreesC. Electrochemical and weight loss measurements were used to evaluate the corrosion resistance in aqueous solutions, and the high-temperature oxidation rate was determined by measuring the pressure decrease in a closed volume. Observations of a high dissolution rate of Fe and SS 301 in deionized water, as well as a high oxidation rate in O-2, can be explained by an increased metal cation transport in the oxide film induced by hydrogen in the metal. However, hydrogen up to a certain concentration in Avesta 353MA was found to increase the resistance to localized corrosion in chloride solution. Pt coating on Fe was found to decrease the oxidation rate and improve scale adherence. The presented results are discussed in view of recent findings of balanced metal cation and oxygen anion transport in protective metal oxides.
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| 31. |
- Wallinder, E, et al.
(författare)
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Vertically sounding ozone lidar system based on a KrF excimer laser
- 1997
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Ingår i: Physica Scripta. Topical Issues. - : IOP Publishing. - 0281-1847. ; 55:6, s. 714-718
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Tidskriftsartikel (refereegranskat)abstract
- A differential absorption (DIAL) lidar system based on a Raman shifted KrF excimer laser was constructed and employed for vertically sounding measurements of tropospheric ozone, This system is described, including a presentation of measurements of Raman shifting efficiencies in hydrogen and deuterium. The performance of the new system was evaluated in measurement campaigns involving two further optical remote-sensing systems: A Nd:YAG/dye laser based lidar and a long-path differential optical absorption spectroscopy (DOAS) system, utilising a high-pressure xenon lamp.
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| 32. |
- Wallinder, Jonas, et al.
(författare)
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Discovery of a novel circulating biomarker in patients with abdominal aortic aneurysm: a pilot study using a proteomic approach.
- 2012
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Ingår i: Clinical and translational science. - : Wiley. - 1752-8062 .- 1752-8054. ; 5:1, s. 56-9
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal aortic aneurysm (AAA) is a common condition with high mortality when ruptured. Most clinicians agree that small AAAs are best managed by ultrasonographic surveillance. However, it has been stated in recent reviews that a serum/plasma biomarker that predicts AAA rupture risk would be a powerful tool in stratifying patients with small AAA. Identification of such circulating biomarkers has been to date unsuccessful. In this study, we used a proteomic approach to find new, potential plasma AAA biomarker candidates. Prefractionated plasma samples were analyzed by two-dimensional differential in-gel electrophoresis to identify differentially expressed proteins between four patients with small AAA and four controls without aneurysm. Protein spots that differed significantly between patients and controls were selected and identified by mass spectrometry. Three protein spots had significantly different expression between patients and controls. The most interesting finding was that patients with small AAA had increased levels of the enzyme glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) compared with the controls without aneurysm. In conclusion, by using a proteomic approach, this pilot-study provides evidence of GPI-PLD as a novel potential plasma biomarker for AAA.
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| 33. |
- Wallinder, Jonas, et al.
(författare)
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Early inflammatory response in patients with ruptured abdominal aortic aneurysm.
- 2010
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Ingår i: Vascular and endovascular surgery. - : SAGE Publications. - 1938-9116 .- 1538-5744. ; 44:1, s. 32-5
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Tidskriftsartikel (refereegranskat)abstract
- Multiorgan failure is the main cause of death in patients operated for ruptured abdominal aortic aneurysm (rAAA). The systemic inflammatory response plays a central role in the generation and maintenance of multiorgan dysfunction. The aim of the current study was to investigate the inflammatory response preoperatively in patients with ruptured and nonruptured AAA in relation to the clinical outcome. A total of 95 patients about to undergo repair of AAA (43 ruptured with shock, 12 ruptured without shock, and 40 elective) and 41 controls without aneurysm matched by age, gender, and smoking habits were investigated by inflammatory markers. There were significantly higher levels of interleukin 6 (IL-6; proinflammatory cytokine) and IL-10 (anti-inflammatory cytokine) in patients operated for ruptured compared to nonruptured AAA. In conclusion, the current data indicate that rupture of an AAA activates the inflammatory system with a compensatory anti-inflammatory response.
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| 34. |
- Wallinder, Jonas, et al.
(författare)
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Haemostatic markers in patients with abdominal aortic aneurysm and the impact of aneurysm size
- 2009
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 124:4, s. 423-6
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Abdominal aortic aneurysm is a common condition with high mortality when rupturing. However, the condition is also associated with nonaneurysmal cardiovascular mortality. A possible contributing mechanism for the thrombosis related cardiovascular mortality is an imbalance between the activation of the coagulation system and the fibrinolytic system. The aim of the present study was to investigate haemostatic markers in patients with nonruptured abdominal aortic aneurysm with special regard to the influence of aneurysm size and smoking habits. METHODS: Seventy-eight patients with infrarenal aortic aneurysm and forty-one controls without aneurysm matched by age, gender and smoking habits were studied. Thrombin-antithrombin (TAT), prothrombin fragment 1+2 (F 1+2)--markers of thrombin generation, and von Willebrand factor antigen (vWFag)--considered as a reliable marker of endothelial dysfunction--were measured. Plasma levels of tissue plasminogen activator antigen (tPAag), and plasminogen activator inhibitor type 1 (PAI-1) were measured as markers of fibrinolytic activity. D-dimer, a marker of fibrin turnover, was also measured. RESULTS: There were significantly higher levels of TAT and D-dimer in patients with abdominal aortic aneurysm. The highest level of TAT and D-dimer were detected in patients with large compared to small AAA. CONCLUSIONS: The present data indicate a state of activated coagulation in patients with abdominal aortic aneurysm which is dependent by aneurysm size. The activated coagulation in AAA patients could contribute to an increased cardiovascular risk in patients also with small AAA. The possible impact of secondary prevention apart from smoking cessation has to be further evaluated and is maybe as important as finding patients at risk of rupture.
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| 35. |
- Wallinder, Jonas, et al.
(författare)
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Proinflammatory and anti-inflammatory cytokine balance in patients with abdominal aortic aneurysm and the impact of aneurysm size
- 2009
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Ingår i: Vascular and endovascular surgery. - : SAGE Publications. - 1538-5744 .- 1938-9116. ; 43:3, s. 258-61
-
Tidskriftsartikel (refereegranskat)abstract
- Abdominal aortic aneurysm is a common condition with high mortality due to rupture; however, the condition also is associated with nonaneurysmal cardiovascular mortality. A possible contributing mechanism for the cardiovascular mortality is an imbalance between the proinflammatory and anti-inflammatory systemic response. In the present study, 78 patients with abdominal aortic aneurysm and 41 controls without aneurysm matched by age, gender and smoking habits were investigated. Cytokines such as interleukin-6, interleukin-10, and monocyte chemoattractant protein-1 were measured in plasma. There was significantly higher level of interleukin-6 in patients with AAA compared to controls. The interleukin-6/ interleukin-10 ratio was highest in patients with large compared to small abdominal aortic aneurysm. In conclusion, the present data indicate a proinflammatory response and a proinflammatory to antiinflammatory imbalance in patients with abdominal aortic aneurysm which is dependent by aneurysm size.
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| 36. |
- Westin, E. M., et al.
(författare)
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New weldable 316L stainless flux-cored wires with reduced Cr(VI) fume emissions : part 2—round robin creating fume emission data sheets
- 2021
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Ingår i: Welding in the World. - : Springer Nature. - 0043-2288 .- 1878-6669. ; 65:12, s. 2339-2348
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Tidskriftsartikel (refereegranskat)abstract
- Welding fumes have been found to be carcinogenic and stainless steel welders may be at higher risk due to increased formation of hexavalent chromium (Cr(VI)). The slag-shielded methods, identified to generate most airborne particles and Cr(VI), would potentially be most harmful. With ever-stricter limits set to protect workers, measures to minimize human exposure become crucial. Austenitic stainless steel flux-cored wires of 316L type have been developed with the aim to reduce the toxicity of the welding fume without compromised usability. Collected particles were compared with fumes formed using solid, metal-cored, and standard flux-cored wires. In part 1, the new wires were concluded to have improved weldability, to generate even less Cr(VI) in wt.-% than with solid wire and to be less acute toxic in cultured human bronchial epithelial cells as compared to standard flux-cored wires. In part 2, two additional institutes created fume emission datasheets for the same wires for correlation with the fume data obtained in part 1. The reported values showed large variations between the three laboratories, having a significant effect on the standard deviation. This is suggested to be the result of different welding parameters and various ways to collect and analyze the fume. More stringent specifications on parameter settings and fume collection would be required to increase the accuracy. This means that at present, it may not be possible to compare fume data on datasheets from two different wire producers and care should be taken in interpretation of values given in the available literature. Nevertheless, the laboratories confirmed the same trends for Cr(VI) as presented in part 1.
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| 37. |
- Westin, E. M., et al.
(författare)
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New weldable 316L stainless flux-cored wires with reduced Cr(VI) fume emissions : part 1—health aspects of particle composition and release of metals
- 2021
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Ingår i: Welding in the World. - : Springer Nature. - 0043-2288 .- 1878-6669. ; 65:12, s. 2319-2337
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Tidskriftsartikel (refereegranskat)abstract
- Welding fumes have been found to be carcinogenic and stainless steel welders may be at higher risk due to increased formation of hexavalent chromium (Cr(VI)). The slag-shielded methods, identified to generate most airborne particles and Cr(VI), would potentially be most harmful. With ever-stricter limits set to protect workers, measures to minimize human exposure become crucial. Austenitic stainless steel flux-cored wires of 316L type have been developed with the aim to reduce the toxicity of the welding fume without compromised usability. Collected particles were compared with fumes formed using solid, metal-cored, and standard flux-cored wires. The size, morphology, and composition were characterized with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). Total metal concentrations and released amounts of metals (Cr, Cr(VI), Ni, Mn, Fe) were investigated after complete digestion in aqua regia and after incubation in phosphate buffered saline (PBS) by means of flame furnace atomic absorption spectroscopy (AAS), inductively coupled plasma mass spectroscopy (ICP-MS), and UV–vis spectroscopy. The cytotoxicity of the particles was assessed with the Alamar blue assay for cell viability using cultured human bronchial epithelial cells (HBEC-3kt). The findings correlate well with previous in vitro toxicity studies for standard and experimental wires. The new optimized 316L-type flux-cored wires showed improved weldability and generated less Cr(VI) in wt.-% than with solid wire. The respirable particles were confirmed to be less acute toxic in HBEC-3kt cells as compared to standard flux-cored wires. The highest cell viability (survival rate) was observed for the metal-cored wire.
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