| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 3. |
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| 4. |
- Bjursten, Henrik, et al.
(författare)
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Circulating particles during cardiac surgery.
- 2009
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293.
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Tidskriftsartikel (refereegranskat)abstract
- Shed blood is known to be a source of lipid micro-emboli in cardiac surgery. The aim of this study was to characterize the occurrence of these particles at different stages of the operation, and to study their occurrence in the circulation at multiple time-points after the retransfusion of shed blood. 44 patients undergoing routine surgery with cardiopulmonary bypass were included. Blood was sampled from the surgical field at different sampling locations during the operation. Shed blood was collected in a transfusion bag and retransfused. After which, blood was sampled from the arterial line of the heart-lung machine. A Coulter counter was used for particle determinion. The mean volume of shed blood collected was 340+/-215 ml. Particles in the size range 10-60 microm were found at varying concentrations, with the highest concentrations being found in blood collected after cannulation and from the pleura. After retransfusion of this blood, a biphasic response was seen in the blood drawn from the efferent line of the heart-lung machine. Particles are found in shed blood at all times during cardiac surgery, and when this blood was retransfused an increase was seen in particle concentration in the heart-lung machine. Keywords: Particles; Lipid particles; Circulation; Shed mediastinal blood.
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| 5. |
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| 6. |
- Nilsson, Johan, et al.
(författare)
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A randomized study of coronary artery bypass surgery performed with the Resting Heart™ System utilizing a low vs a standard dosage of heparin.
- 2012
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 15:5, s. 834-839
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Allogeneic blood transfusion and reoperation for postoperative bleeding after the coronary artery bypass grafting have a negative impact on the patient outcome. This study aimed at evaluating the effects of reduced doses of heparin and protamine on the patient outcome, using a heparin-coated mini-cardiopulmonary bypass (CPB) system. METHODS: Sixty patients undergoing elective first-time CPB were prospectively randomized either to have a reduced systemic heparinization [activated clotting time (ACT) = 250 s] or to a control group perfused with a full heparin dose (ACT = 420 s). Blood transfusions, ventilation time, early postoperative bleeding, ICU stay, reoperations for bleeding, postoperative cognitive status and the level of mobilization were registered. RESULTS: Twenty-nine patients were randomized to the control group, 27 patients to the low-dose group and 4 patients were excluded because of protocol violations. Four patients in the control group received a total of 10 units of packed red blood cells, and in the low-dose group, no transfusions were given, P = 0.046. No patient was reoperated because of bleeding. The ICU stay was significantly shorter in the low-dose group (8.4 vs 13.7 h, P = 0.020), less dependent on oxygen on the first postoperative day (78 vs 97%, P = 0.034), better mobilized (89 vs 59%, P = 0.006) and had less pain (visual analogue scale 2.0 vs 3.5, P = 0.019) compared with the control group. CONCLUSIONS: The use of a mini-CPB system combined with a low dose of heparin reduced the need for blood transfusions and may facilitate the faster mobilization of the patients.
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| 7. |
- Andersson, Arne, et al.
(författare)
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Amyloid Deposition in Transplanted Human Pancreatic Islets : A Conceivable Cause of Their Long-Term Failure
- 2008
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Ingår i: EXPERIMENTAL DIABETES RESEARCH. - : Hindawi Limited. - 1687-5214 .- 1687-5303. ; 2008:562985
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Tidskriftsartikel (refereegranskat)abstract
- Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the beta-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Enberg, Sofia, et al.
(författare)
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Some causes of formation of colour during storage of hydrogen-peroxide bleached Norway spruce mechanical pulp
- 2014
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Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 29:2, s. 356-366
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Tidskriftsartikel (refereegranskat)abstract
- The discolouration of hydrogen-peroxide bleached Norway spruce mechanical pulp during storage in mill systems was studied and the contributions of process water, iron and dyes were evaluated over the visible spectrum. Washing of the pulp made it less sensitive to storage, possibly due to the removal of extractives, lignin-like substances, iron and pulp fines. Storage in white water gave extensive discolouration with a shoulder in the absorption spectrum at around 550-650 nm. Most of the colour was associated with pulp fines or filler but some colour was also found in smaller fractions and in the water phase. The addition of ferric ions increased the light absorption coefficient during storage, initially at short wavelengths and then over the whole spectrum, but could not explain the increased absorption at 550-650 nm and could not be the only cause of the darkening in the mill system. A cationic basic violet dye gave a shoulder in the absorption spectrum similar to that in the mill system, but the absorption in this area did not increase during storage. Model calculations indicate that ferric ions together with violet and red dyes could explain a major part, but not all, of the colour observed in the mill system after storage. The darkening not accounted for at longer wavelengths and around 550-650 nm is suggested to be related to fines and fillers including dissolved and colloidal substances associated with these particles.
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| 12. |
- Enberg, Sofia
(författare)
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Storage of Hydrogen Peroxide Bleached Mechanical Pulp : Reduction in Reflectance over the Visible Spectrum
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this thesis is to determine possible causes of the darkening of hydrogen peroxide bleached mechanical pulp over the visible spectrum and their relative contributions. It focuses on both process conditions and the composition of the pulp and the dilution water, including additions or losses of material along the process line from the bleach tower to the paper machine.A mapping of the optical properties of the pulp along the process showed that the fine fraction of the pulp darkened more than the long fibre fraction. Simulation of retention times of different fractions showed that the main part of the fine material is retained in the paper within a few hours, a small part might circulate for considerably longer time and may therefore be strongly coloured.Storage trials were mainly performed using a hydrogen peroxide bleached mechanical pulp intended for SC paper made of Norway spruce (Picea abies), sampled on one occasion and stored in a freezer. Unwashed or well-washed pulp was stored in distilled water or in different process waters. Some complementary trials were included, e.g. unbleached pulp.Time and temperature were the process variables that gave the strongest darkening of the pulp, as expected, both in a clean and a more process-like system, whereas pH only had an effect in the presence of process waters; the highest brightness stability was seen at a pH around 5.5–6.0.The darkening was due to an increase in the light absorption coefficient (k) beginning at short wavelengths, but after longer storage times the increase in kλ also became noticeable at longer wavelengths. The colour (CIE L*, a*, b*) of the pulp changed towards red and yellow, initially more towards red and then more towards yellow. These changes were clearly visible.Washing of the bleached pulp made it less sensitive to storage; possibly due to the removal of extractives, lignin-like substances, metals and pulp fines. This washing had little effect before storage and the amount of material removed was small.The pulp darkened more when stored in process waters compared to distilled water. Apart from fibres, most of the colour was associated with pulp fines or filler but some colour was also found in the dissolved and colloidal fractions. At an increased pulp consistency, the increase in k460 was smaller.Storage in white water from the paper machine gave extensive discolouration with a shoulder in the absorption spectrum around 550–650 nm, which increased with time. The addition of ferric ions increased the light absorption coefficient during storage, but could not explain the increased absorption at 550–650 nm nor could it be the only cause of the darkening in the mill system. A cationic basic violet dye gave a shoulder in the absorption spectrum similar to that of the mill system, but the absorption of the dye did not increase during storage. Model calculations indicate, but do not prove, that ferric ions together with violet and red dyes could have played a major, but not exclusive role in the colour observed in the mill system after storage. The darkening not accounted for, at longer wavelengths and around 550–650 nm, is suggested to be related to fines and fillers including dissolved and colloidal substances associated with these particles.A method to produce representative sheets for determination of optical properties of mechanical pulps was developed. The new method makes it possible to follow changes in light absorption and light scattering coefficients over the visible range of wavelengths. It is approximately six times faster than standard methods, reduces the risk of additional darkening of the sample and can be used with small pulp quantities.The deviation from the expected linear behaviour of the light scattering coefficient, s, at wavelengths corresponding to strong light absorption has been studied using the Kubelka-Munk model and the angular resolved DORT2002 radiative transfer solution method. The decrease in s could not be explained by errors introduced in the Kubelka-Munk modelling by anisotropic scattering.
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| 13. |
- Enberg, Sofia, et al.
(författare)
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The influence of process waters on optical properties during storage of hydrogen-peroxide bleached Norway spruce mechanical pulp
- 2014
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Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 29:2, s. 344-355
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the causes behind the formation of colour in mill systems, the effect of different process waters on the optical properties of hydrogen-peroxide bleached Norway spruce mechanical pulp during storage was studied. The influence of process water type, temperature, time, pulp consistency and pH was evaluated over the visible range of wavelengths. The darkening was more pronounced when pulp was stored in process waters compared to in distilled water. Increased temperature and prolonged storage times increased the darkening as expected, whereas a higher storage consistency gave less darkening than a lower storage consistency (15% compared to 5%). The pH value that gave the lowest brightness reduction and a minimum in Delta k(460) was found to be 5.5-6.0. Storage of pulp in white water from the paper machine resulted in a broad shoulder in the k spectra indicating colour formation related to the particles in this water. Part of this shoulder in absorption spectra was related to added dyes, but the increase in absorption with time is likely to be caused by some other colour formation. The colour measured as a*, b* showed that the storage changed the colour of the pulp towards red and yellow, and initially more towards red.
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| 14. |
- Engstrand, Per, Professor, 1955-, et al.
(författare)
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Decrease in strengthalong a process line for SC paper
- 2019
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Ingår i: Fundamental Mechanical Pulp Research Seminar, FMPRS2019, Norrköping, SwedenArranged by Mid Sweden University in cooperatrion with Holmen AB, Valmet AB, AF AB and Treesearch..
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Konferensbidrag (refereegranskat)
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| 15. |
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| 16. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia
- 2018
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:10, s. 2117-2125
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.
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| 17. |
- Hellström, Mikael, et al.
(författare)
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Styra meningsfullt med mål
- 2009
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Ingår i: Ett smörgåsbord med ekonomistyrning och redovisning. - 9185113395 - 9789185113392 ; Nr 113, s. 207-229
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- I denna artikel belyses några kommunala ambitioner att styra med mål. En av frågorna vi ställer oss är varför vissa organisationer i den kommunala och landstingskommunala sektorn förefaller styras mer effektivt med mål än andra. Vad är det som gör att vissa offentliga organisationer vinner den ena utmärkelsen efter den andra avseende till exempel servicekvalité och styrning. Med vilken substans pratas det om att – X-kommun har lyckats göra något bra och på Y-sjukhus har de verkligen vänt på skutan. Är det några speciella beslut som tas? Vissa beslut förefaller leda till en styrning med mål som är bättre, mer effektiv än andra. Frågorna om mål och styrning är onekligen många. Syftet med denna artikel är att beskriva och analysera hur man kan styra effektivt med mål.
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| 18. |
- Karlsson, Anette, et al.
(författare)
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Determining optical properties of mechanical pulps : Sheetmaking procedure and investigation of different ways to evaluate light absorption
- 2012
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Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 27:3, s. 531-541
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Tidskriftsartikel (refereegranskat)abstract
- A method to produce representative sheets for determination of optical properties of mechanical pulps has been developed. It reduces the risk of contamination and discoloration and can be used with small pulp quantities. The deviation from the expected linear behaviour of the light scattering coefficient, s, at wavelengths corresponding to strong light absorption, has been studied using the Kubelka-Munk model and the angular resolved DORT2002 radiative transfer solution method. This decrease in s could not be explained by errors introduced in the Kubelka-Munk modelling by anisotropic scattering. Linear extrapolation of s can therefore not be justified as a way to obtain a more correct light absorption coefficient, k. For thepulps studied, the decrease in s at short wavelengths had little effect on k at 457 nm.
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| 19. |
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| 20. |
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| 21. |
- Karlsson, Anette, et al.
(författare)
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Strategies to reduce heat-induced darkening for enhanced bleachability of mechanical pulps
- 2014
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Ingår i: Appita journal. - 1038-6807. ; 67:1, s. 50-57
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Tidskriftsartikel (refereegranskat)abstract
- Under mechanical pulping conditions, elevated temperature initiates reactions in the wood constituents resulting in the formation of coloured structures. In an attempt to reduce the formation of colour, a number of additives have been examined to assess their ability to inhibit heat-induced darkening of a Norway spruce (Picea abies) stone groundwood (SGW) pulp. SGW pulp was used as a model pulp with the purpose of imitating a thermomechanical pulp (IMP). The heat-treated SGW pulp, both with and without additives present, was subsequently bleached with 4.5% hydrogen peroxide at high pulp consistency and with varying alkali charges in order to examine the hydrogen peroxide bleachability of such pulps. Heat treatment at 170 °C resulted in a loss of brightness of about 4% ISO after heating for 60 seconds. The reduction in brightness could only partly be regained through high consistency hydrogen peroxide bleaching; the SGW pulp displayed a brightness of 83.7% ISO whereas the heat-treated SGW pulp reached a brightness of 80.4% ISO. Heat treatment with a low addition rate (1 %) of alkaline hydrogen peroxide, sodium bisulfite or sodium sulfite, with a subsequent hydrogen peroxide bleaching stage, resulted in an improved bleached brightness of about 81.6% ISO, i.e. the loss of brightness due to heat was still approximately 2% ISO. Sodium borohydride (1 %) did not suppress the thermal darkening but improved the bleached brightness by approximately 2% ISO compared to the heat-treated SGW pulp and resulted in a brightness of 82.6% ISO. Addition of a chelating agent (DTPA, 0.11 and 0.45%) and the radical scavengers phthalic hydrazide (1 %) and 1 -hexanol (1 %) suppressed the heat-induced darkening somewhat but did not improve the hydrogen peroxide bleachability to any noticeable extent. Addition of citric acid (0.6%) did not suppress the thermal darkening and resulted in impaired bleachability.
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| 22. |
- Krasse, Per, et al.
(författare)
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Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri
- 2006
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Ingår i: Swedish Dental Journal. - : Swedish Dental Association. - 0347-9994. ; 30:2, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- Avsikten med studien var att undersöka om dagligt användande av ett probiotiskt kosttillskott innehållande Lactobacillus reuteri kunde ge positiva effekter på patienter med måttlig eller svår gingivit. I försöket testades placebotuggummi mot 2 olika L. reuteri formuleringar (LR-1 och LR-2) innehållande 100 miljoner laktobaciller per tuggummi. Tuggummi togs 2 gånger per gång, på morgonen och på kvällen efter tandborstning. Studien var dubbelblind, randomiserad och löpte över 2 veckor. Totalt deltog 59 patienter. Två tandytor på varje patient utvaldes och gingival index och plack index mättes för varje yta, både startdagen och efter 2 veckor. För att minimera risken för observatörsberoende bedömning av index utfördes alla bedömningar på en och samma dag av en enda observatör, både vid start och avslut. Tandytorna fotograferades också för att ge ytterligare konsistens i bedömningen. Efter bedömning av index, rengjordes samtliga tandytor och patienterna instruerades av tandhygienist om korrekt tandborstning och behovet av dagligt användande av tandtråd. Salivprover togs både före och efter test behandling för att avgöra skillnader i laktobacillpopulationen över tiden. 20 patienter rendomiserades till LR-1, 21 till LR-2 och 18 till placebo. Gingival index förbättrades signifikant i samtliga grupper över de 14 dagarna. LR-1 formuleringen var dessutom signifikant överlägsen placebo. Plackindex var också signifikant förbättrat över tiden i de båda reuteri-grupperna- LR-1 koloniserades i 65% av patienterna och LR-2 i 95%.
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| 23. |
- Li, Suling, et al.
(författare)
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Cytokine-induced Src homology 2 protein (CIS) promotes T cell receptor-mediated proliferation and prolongs survival of activated T cells.
- 2000
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 191:6, s. 985-994
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Tidskriftsartikel (refereegranskat)abstract
- Members of the suppressor of cytokine signaling (SOCS) family were discovered as negative regulators of cytokine signaling by inhibition of the Janus kinase–signal transducer and activator of transcription (Jak-STAT) pathway. Among them, cytokine-induced Src homology 2 (SH2) protein (CIS) was found to inhibit the interleukin 3– and erythropietin-mediated STAT5 signaling pathway. However, involvement of SOCS proteins in other signaling pathways is still unknown. This study shows that the expression of CIS is selectively induced in T cells after T cell receptor (TCR) stimulation. In transgenic mice, with selective expression of CIS in CD4 T cells, elevated CIS strongly promotes TCR-mediated proliferation and cytokine production in vitro, and superantigen-induced T cell activation in vivo. Forced expression of CIS also prolongs survival of CD4 T cells after TCR activation. Molecular events immediately downstream from the TCR are not changed in CIS-expressing CD4 T cells, but activation of mitogen-activated protein (MAP) kinase pathways by TCR stimulation is significantly enhanced. Together with the increased MAP kinase activation, a direct interaction of CIS and protein kinase Cθ was also demonstrated. These results suggest that CIS is one of the important regulators of TCR-mediated T cell activation. The functions of CIS, enhancing TCR signaling and inhibiting cytokine signaling, may be important in the regulation of immune response and homeostasis.
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| 24. |
- Linder, Adam, et al.
(författare)
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Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department
- 2015
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS and WILKINS. - 0090-3493 .- 1530-0293. ; 43:11, s. 2378-2386
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (greater than 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.
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| 25. |
- Lindstedt Ingemansson, Sandra, et al.
(författare)
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A compare between myocardial topical negative pressure levels of-25 mmHg and-50 mmHg in a porcine model
- 2008
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 8:14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Topical negative pressure (TNP), widely used in wound therapy, is known to stimulate wound edge blood flow, granulation tissue formation, angiogenesis, and revascularization. We have previously shown that application of a TNP of -50 mmHg to the myocardium significantly increases microvascular blood flow in the underlying tissue. We have also shown that a myocardial TNP levels between -75 mmHg and -150 mmHg do not induce microvascular blood flow changes in the underlying myocardium. The present study was designed to elucidate the difference between -25 mmHg and -50 mmHg TNP on microvascular flow in normal and ischemic myocardium. Methods: Six pigs underwent median sternotomy. The microvascular blood flow in the myocardium was recorded before and after the application of TNP using laser Doppler flowmetry. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium), and after 20 minutes of LAD occlusion (ischemic myocardium). Results: A TNP of -25 mmHg significantly increased microvascular blood flow in both normal (from 263.3 +/- 62.8 PU before, to 380.0 +/- 80.6 PU after TNP application, *p = 0.03) and ischemic myocardium (from 58.8 +/- 17.7 PU before, to 85.8 +/- 20.9 PU after TNP application, *p = 0.04). A TNP of -50 mmHg also significantly increased microvascular blood flow in both normal (from 174.2 +/- 20.8 PU before, to 240.0 +/- 34.4 PU after TNP application, *p = 0.02) and ischemic myocardium (from 44.5 +/- 14.0 PU before, to 106.2 +/- 26.6 PU after TNP application, **p = 0.01). Conclusion: Topical negative pressure of -25 mmHg and -50 mmHg both induced a significant increase in microvascular blood flow in normal and in ischemic myocardium. The increase in microvascular blood flow was larger when using -25 mmHg on normal myocardium, and was larger when using -50 mmHg on ischemic myocardium; however these differences were not statistically significant.
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| 26. |
- Logenius, Louise, et al.
(författare)
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Improved hydrogen peroxide bleaching of mechanical pulps using carbon dioxide in combination with sodium and magnesium based alkali sources
- 2011
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Ingår i: 16th International Symposium on Wood, Fiber and Pulping Chemistry - Proceedings, ISWFPC. ; 1, s. 741-745, s. 741-745
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Konferensbidrag (refereegranskat)abstract
- The pH-profile in the hydrogen peroxide bleaching stage of a Norway spruce thermomechanical pulp was levelled out by using carbon dioxide in combination with sodium or magnesium based alkali sources. Addition of carbon dioxide when magnesium hydroxide was used as the alkali source increased the pulp brightness with up to 1.5 brightness units when the bleaching was performed at 70 °C. When the temperature was increased from 70°C to 90 °C the brightness was increased with about two brightness units, addition of carbon dioxide increased it further. The residual hydrogen peroxide and the chemical oxygen demand (COD) levels were not affected as a consequence of the carbon dioxide addition. In the experiments where sodium hydroxide was used as the alkali source, addition of carbon dioxide lowered the pH that resulted in a decreased COD level, a slightly lower brightness level and, to some extent, an increased residual hydrogen peroxide level.
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| 27. |
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| 28. |
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| 29. |
- Mälarstig, Anders, et al.
(författare)
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Variants of the interferon regulatory factor 5 gene regulate expression of IRF5 mRNA in atherosclerotic tissue but are not associated with myocardial infarction
- 2008
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 28:5, s. 975-982
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Signaling events after activation of toll-like receptors (TLRs) are important mechanisms promoting inflammation in the atherosclerotic plaque. INF regulatory factor 5 (IRF5) is one of the mediators of downstream effects of TLRs. Several single nucleotide polymorphisms (SNPs) in the IRF5 gene have been found to be associated with systemic lupus erythematosus. METHODS AND RESULTS: We examined IRF5 mRNA expression in carotid atherosclerotic tissue (n=99) and the case-control association between SNPs in the IRF5 gene with myocardial infarction (MI) (n=376+387) and unstable coronary artery disease (CAD) (n=3101+445). Among unstable CAD patients, association of IRF5 SNPs with recurrent coronary events (n=401) was also investigated. The IRF5 mRNA expression was increased in atherosclerotic tissue compared with control tissue (P<0.001). Significant associations with IRF5 expression was observed for 6 of 10 SNPs in the study. However, the IRF5 SNPs examined were neither associated with the risk of precocious MI, nor with unstable CAD or risk of recurrent cardiovascular events in unstable CAD patients. CONCLUSIONS: IRF5 mRNA is expressed in cells in atherosclerotic tissue and its expression is modified by SNPs in the IRF5 gene. Genetic variation at the IRF5 locus was, however, not associated with CAD or related phenotypes.
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| 30. |
- Nelsson, Erik, et al.
(författare)
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Low dosage sulfite pretreatment at different refining temperatures in mill scale TMP production
- 2017
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Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 32:1, s. 59-69
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of low dosage sodium sulfite ( Na2SO3) pretreatment (0, 0.6 and 1.2% on bone dry wood, pH 9) at two different refining temperatures (4.6 and 6.4 bar(g) refiner housing pressure) were evaluated for production of thermomechanical pulp with a double disc refiner in mill scale using Norway spruce wood at Braviken paper mill (Holmen Paper AB, Sweden). The sulfonate content of the pulps was not affected by the different refining temperatures and was 0.29% (as Na2SO3 equivalents) for the highest sulfite addition.Tensile index at constant SEC was increased by 3.2 Nm/g when the refining temperature was increased, and by 8.6 Nm/g when 1.2% sodium sulfite was added. The effects were additive and led to an increase in tensile index of similar to 12 Nm/g at constant SEC when combined and would enable a reduction in SEC of 380 kWh/bdt (similar to 20%) to similar tensile index. The degree of delamination and internal fibrillation of the fibers was increased by both increased refining temperature and sulfite addition.Pulp brightness was slightly reduced (<= 0.4% ISO) by increased refining temperature and increased (2-3% ISO), when sodium sulfite was added. Spectra of reflectance factors (360-740 nm) were used to study the optical properties of produced pulps.
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| 31. |
- Nelsson, E., et al.
(författare)
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Mill scale production of TMP with double disk refining-The effects of a mild sulfonation, atmospheric preheating and refining temperatures
- 2016
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Ingår i: International Mechanical Pulping Conference 2016, IMPC 2016. - : TAPPI Press. - 9781510830738 ; , s. 249-259
-
Konferensbidrag (refereegranskat)abstract
- The aim of this work was to study the effects of a mild dosage of sodium sulfite in chip impregnation at diffen temperatures during atmospheric preheating and during refining for production of TMP for printing papers usi high intensity double disk refining. Two trials were performed in the 800 bdt/day double disc line at I Braviken paper mill (Holmen Paper AB, Sweden) using Norway spruce chips. During the trials, chips w( impregnated in an Impressafiner where chips were preheated at 1.8 bar(g) for a few seconds and th compressed before impregnation. During impregnation, sodium sulfite was added to chips at pH 9 in dosages 0.6 or 1.2%. Reference pulps without addition of sulfite were also produced. In the first trial, the effect different temperatures and retention times (80°C for 6 minutes vs. 96°C for 9 minutes) in the atmosphe preheating bin following impregnation was evaluated both with and without the addition of 1.2% sodium sulf In the second trial, the effect of different refining temperatures (refiner house pressures of 4.6 or 6.4 bar(g), 1 or 167°C) was evaluated with different additions of sodium sulfite (0.0, 0.6 or 1,2%) during impregnation. The results from the two trials showed that the increase in refiner house pressure increased the tensile index pulps both with and without addition of sodium sulfite, when compared at certain SEC. However, the increase preheater bin temperature and retention time did not increase the tensile index of pulps but rather led to a sm reduction in tensile index when combined with an addition of 1.2% sodium sulfite. The two different methc used to increase the temperature in the system led to different effects in the disc gap at certain SEC. The disc j temperature was increased by both methods but disc gap was only reduced at certain SEC when the refini temperature was increased by increasing the refiner housing pressure. The difference in the effect on the disc j may hold the answer to the different effects seen in tensile index.
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| 32. |
- Nilsson, David, et al.
(författare)
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Endothelin receptor-mediated vasodilatation: Effects of organ culture.
- 2008
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 579:1-3, s. 233-240
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Tidskriftsartikel (refereegranskat)abstract
- Culture of intact arteries is a frequently employed experimental model for investigating the mechanisms governing the regulation of vascular endothelin receptors. Endothelin type A (ETA) and type B (ETB) receptors on vascular smooth muscle cells are up-regulated in organ culture and the enhanced vasoconstriction mimics the changes that occur in cardiovascular disease. The effect of organ culture on endothelial dilatory endothelin ETB receptors is not known. We hypothesize that organ culture decreases the endothelin receptor-mediated dilatation and that this is one possible mechanism by which the effects of the endothelin in blood vessels are altered during culture. Porcine coronary arteries were studied before and after 24 h of culture, using in vitro pharmacology and immunofluorescence. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ETA and ETB receptor effects, and the antagonists, Nω-nitro-l-arginine (l-NOARG) for nitric oxide (NO), indomethacin for prostaglandins and charybdotoxin in combination with apamin for endothelium-derived hyperpolarizing factor (EDHF), were used to study the endothelium-derived dilatory mediators. Organ culture induced up-regulation of the sarafotoxin 6c (ETB receptor agonist) and endothelin-1 (ETA receptor agonist) elicited vasoconstriction. The sarafotoxin 6c contraction was stronger after endothelium denudation, suggesting endothelium-dependent dilatation. The endothelin-1 contraction was not affected by endothelium denudation. The increase in sarafotoxin 6c contraction after removal of the endothelium was more pronounced before than after organ culture, suggesting down-regulated endothelial endothelin ETB receptors. Also, the immunofluorescence staining intensities for endothelial endothelin ETB receptors were higher before than after organ culture. Pre-incubation with inhibitors for dilatory mediators suggested that both NO and EDHF play a vasodilatory role, while prostaglandins are not involved. In conclusion, endothelial endothelin ETB receptors induce NO and EDHF mediated vasodilatation in porcine coronary arteries. In organ culture, endothelial endothelin ETB receptors are down-regulated, mimicking the changes that occur in cardiovascular disease. Down-regulation of endothelial endothelin ETB receptors may in part explain the increased endothelin ETB receptor-mediated vasoconstriction frequently studied in organ culture.
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| 33. |
- Nilsson, David, et al.
(författare)
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Increased ET(A) and ET(B) receptor contraction in the left internal mammary artery from patients with hypertension.
- 2008
-
Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 22:3, s. 226-229
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Tidskriftsartikel (refereegranskat)abstract
- Patients with hypertension have an increased activity in the endothelin system and an increased vascular tone, which predisposes them to target organ damage. In the present study, in vitro pharmacology, real-time PCR and immunofluorescence techniques were used to show enhanced endothelin type A (ETA) and type B (ETB) receptor contraction and expression in the left internal mammary artery from patients with hypertension as compared to normotensive patients. These receptors may be important in the pathophysiology of hypertension.
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| 34. |
- Nilsson, David, et al.
(författare)
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Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways.
- 2008
-
Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Up-regulation of vascular endothelin type B (ETB) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, ex vivo, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ETB receptors in human internal mammary arteries. METHODS: Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using in vitro pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ETA and ETB receptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists. RESULTS: The endohtelin-1-induced contraction (after endothelin ETB receptor desensitization) and the endothelin ETA receptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ETB receptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 microM bisindolylmaleimide I and 10 microM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 microM SB203580, 10 microM PD98059 and 10 microM SP600125, respectively). CONCLUSION: In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ETB receptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ETB receptor changes in cardiovascular disease.
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| 35. |
- Offstad, Jon, et al.
(författare)
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The Scandinavian multicenter hemodynamic evaluation of the SJM Regent aortic valve
- 2011
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 6:163
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Tidskriftsartikel (refereegranskat)abstract
- Background: 112 patients who received small and medium sized St.Jude Regent heart valves (19-25 mm) at 7 Scandinavian centers were studied between January 2003 and February 2005 to obtain non-invasive data regarding the hemodynamic performance at rest and during Dobutamine stress echocardiography (DSE) testing one year after surgery. Material and methods: 46 woman and 66 men, aged 61.8 +/- 9.7 (18-75) years, were operated on for aortic regurgitation (17), stenosis (65), or mixed dysfunction (30). Valve sizes were 19 mm (6), 21 mm (33), 23 mm (41), 25 mm (30). Two patients receiving size 27 valves were excluded from the hemodynamic evaluation. Pledgets were used in 100 patients, everted mattress in 66 and simple interrupted sutures in 21. Valve orientation varied and was dependent on the surgeons' choice. 34 patients (30.4%) underwent concomitant coronary artery surgery. Results: There were two early deaths (1.8%) and three late deaths, one because of pancreatic cancer. Late events during follow-up were: non structural dysfunction (1), bleeding (2), thromboembolism (2). At one year follow up 93% of the patients were in NYHA classes 1-2 versus 47.8% preoperatively. Dobutamine stress echocardiography (DSE) was performed in a total of 66 and maximal peak stress was reached in 61 patients. During DSE testing, the following statistically significant changes took place: Heart rate increased by 73.0%, cardiac output by 85.5%, left ventriclular ejection fraction by 19.6%, and maximal mean prosthetic transvalvular gradient by 133.8%, whereas the effective orifice area index did not change. Left ventricular mass fell during one year from 215 +/- 63 to 197 +/- 62 g (p < 0.05). Conclusion: The Dobutamine test induces a substantial stress, well suitable for echocardiographic assessment of prosthesis valve function and can be performed in the majority of the patients. The changes in pressure gradients add to the hemodynamic characteristics of the various valve sizes. In our patients the St. Jude Regent valve performed satisfactory at rest and under pharmacological stress situation.
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| 36. |
- Olofsson, P. S., et al.
(författare)
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Genetic variants of TNFSF4 and risk for carotid artery disease and stroke
- 2009
-
Ingår i: Journal of Molecular Medicine. - New York : Springer. - 0946-2716 .- 1432-1440. ; 87:4, s. 337-346
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Tidskriftsartikel (refereegranskat)abstract
- In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730∈±∈30 vs 330∈±∈65 arbitrary units, p∈<∈0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-α; 460∈±∈110 vs 133∈±∈8 arbitrary units, p∈<∈0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.
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| 37. |
- Oskarsson, Marie E., et al.
(författare)
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In Vivo Seeding and Cross-Seeding of Localized Amyloidosis A Molecular Link between Type 2 Diabetes and Alzheimer Disease
- 2015
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 185:3, s. 834-846
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Tidskriftsartikel (refereegranskat)abstract
- Several proteins have been identified as amyloid forming in humans, and independent of protein origin, the fibrils are morphologically similar. Therefore, there is a potential for structures with amyloid seeding ability to induce both homologous and heterologous fibril growth; thus, molecular interaction can constitute a Link between different amyloid forms. Intravenous injection with preformed fibrils from islet amyloid polypeptide (IAPP), proIAPP, or amyloid-beta (A beta) into human IAPP transgenic mice triggered IAPP amyloid formation in pancreas in 5 of 7 mice in each group, demonstrating that IAPP amyloid could be enhanced through homologous and heterologous seeding with higher efficiency for the former mechanism. Proximity Ligation assay was used for colocalization studies of IAPP and A beta in islet amyloid in type 2 diabetic patients and A beta deposits in brains of patients with Alzheimer disease. All reactivity was not detected in islet amyloid although islet beta cells express A beta PP and convertases necessary for A beta production. By contrast, IAPP and proIAPP were detected in cerebral and vascular A beta deposits, and presence of proximity Ligation signal at both locations showed that the peptides were <40 nm apart. It is not clear whether IAPP present in brain originates from pancreas or is Locally produced. Heterologous seeding between IAPP and All shown here may represent a molecular Link between type 2 diabetes and Alzheimer disease.
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| 38. |
- Palmberg, Ebba, et al.
(författare)
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Metronomic scheduling of imatinib abrogates clonogenicity of neuroblastoma cells and enhances their susceptibility to selected chemotherapeutic drugs in vitro and in vivo
- 2009
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:5, s. 1227-1234
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Tidskriftsartikel (refereegranskat)abstract
- Imatinib is currently in early clinical trials as targeted therapy for relapsed neuroblastomas and other childhood solid tumors expressing platelet-derived growth factor receptors (PDGFR) or c-Kit. Short-term treatment with imatinib in clinically achievable concentrations is ineffective in neuroblastoma in vitro. However, clinically, imatinib is administered daily over long time periods. The effects of combining imatinib with chemotherapy in neuroblastoma are unknown. Here, a panel of neuroblastoma cell lines (n = 5) were studied, representing tumors with different biological (MYCN-amplification +/-) and clinical (drug resistance) features. Using a protracted low-dose treatment schedule (1-3 weeks; 0.5-5microM) imatinib dose-dependently inhibited proliferation and clonogenic survival for all tested cell lines with IC50 <2.5microM. In contrast, short-term treatment (<96 hrs) was ineffective. Low-dose imatinib was synergistic in combination with doxorubicin and caused increased G2/M- and S-phase arrest and apoptosis as evidenced by enhanced caspase-3 activation and sub-G1 DNA accumulation. A significant but less pronounced effect was observed when imatinib was combined with etoposide or vincristine, as opposed to cisplatin, melphalan, or irinotecan. All cell lines expressed PDGFRbeta, whereas no protein expression of PDGFRalpha was detected in MYCN amplified cell lines. PDGF-BB caused PDGFRbeta phosphorylation and partially rescued neuroblastoma cells from doxorubicin-induced apoptosis, in an imatinib-sensitive manner. In vivo, treatment with imatinib in combination with doxorubicin induced a significant growth inhibition of established neuroblastoma xenografts. These findings suggest clinical testing of imatinib in combination with selected chemotherapeutic drugs, in particular doxorubicin, in children with high-risk neuroblastoma.
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| 39. |
- Paulsson, Amalia, et al.
(författare)
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A/B Testing in the Small
- 2022
-
Ingår i: International Conference on Product-Focused Software Process Improvement. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783031213878 - 9783031213885 ; 13709, s. 449-463
-
Konferensbidrag (refereegranskat)abstract
- Previous research on A/B testing and continuous experimentation has mostly focused on large-scale settings with company-external customers. However, work efficiency and satisfaction for company coworkers may be highly related to internal tools and their fit-for-use. In this study, we therefore explore A/B testing for online services exclusively used by company co-workers. We A/B tested two versions of Customer Admin, a tool that helps 34 500 IKEA co-workers to interact with customer data. The study comprised i) stakeholder interviews to understand objectives and phrase the experimentation goals, and ii) A/B test execution where data was collected and processed from approximately 350 users for 33 days. While the user base is relatively large for this internal system, the primary metric data collected was too scarce to allow distinction between the two versions. However, secondary metrics and a user questionnaire suggest that the users are more efficient in the new menu design and that the users prefer it to the old. We conclude that A/B testing requires lots of data, making it less feasible for internal users, also for large, global organizations. Thus, we propose combining quantitative and qualitative evaluation of internal tools and propose further research on how to adapt A/B testing for smaller-scale settings.
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| 40. |
- Paulsson, Björn, 1946-, et al.
(författare)
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Upgrading of infrastructure in order to meet new operation and market demands
- 2017
-
Rapport (refereegranskat)abstract
- The European objective of a modal shift of freight transports to railways will require extensive upgrading of existing railway lines since very few dedicated freight railways are currently being built and existing lines were built for traffic demands at the time of construction. A transition to increased and enhanced railway freight operations can therefore be costly and complicated. To minimize negative effects, a guideline for upgrading was developed within the Capacity4Rail project. This handbook presents the major findings. In particular it outlines different upgrading possibilities and their implications, and details structured approaches to upgrading analyses. It discusses possibilities for upgrading of substructures, bridges, tunnels, and the track structure. In these areas, an overview of challenges and possibilities is presented together with examples of experience from operational upgrading. It concludes that freight line upgrading using a more streamlined approach as outlined in the guideline is a necessity if EU objectives on modal shifts in transportation are to be met. Further, it demonstrates why a political drive is necessary to increase efforts to upgrade freight lines.
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| 41. |
- Paulsson, Johan F, et al.
(författare)
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Real-Time Monitoring of Apoptosis by Caspase-3-Like Protease Induced FRET Reduction Triggered by Amyloid Aggregation
- 2008
-
Ingår i: Experimental Diabetes Research. - : Hindawi Limited. - 1687-5214 .- 1687-5303. ; 2008:865850
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid formation is cytotoxic and can activate the caspase cascade. Here, we monitor caspase-3-like activity as reduction of fluorescence resonance energy transfer (FRET) using the contstruct pFRET2-DEVD containing enhanced cyan fluorescent protin (EYFP) linked by the caspase-3 specific cleavage site residues DEVD. Beta-TC-6 cells were transfected, and the fluoorescence was measured at 440 nm excitation and 535 nm (EYFP) and 480 nm (ECFP) emission wavelength. Cells were incubated with recombinant pro lset Amyloid Polypeptide (rec prolAPP) or the processing metabolites of prolAPP; the N-terminal flanking peptide withIAPP (recN+IAPP); IAPP with the C-terminal flanking peptied (recIAPP+C) and lslet Amyloid Polypeptide (recIAPP). Peptides were added in solubilized from (50 mu M) or as performed amyloid-like fibrils, or as a combination of these. FRET was measured and incubation with a mixture of solubilized peptide and performed fibrils resulted in loss of FRET and apoptosis was determined to occurein cells incubated with recproIAPP (49%), recN+IAPP (46%), recIAPP (72%) and recIAPP+C (59%). These results show that proIAPP and the processing intermediates reside the same cell toxic capacity as IAPP, and they can all have a central role in the reduction of beta-cell number in type 2 diabetes.
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| 42. |
- Paulsson, Kajsa M, et al.
(författare)
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Association of tapasin and COPI provides a mechanism for the retrograde transport of major histocompatibility complex (MHC) class I molecules from the Golgi complex to the endoplasmic reticulum
- 2002
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:21, s. 18266-18271
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Tidskriftsartikel (refereegranskat)abstract
- Tapasin is a subunit of the transporter associated with antigen processing (TAP). It associates with the major histocompatibility complex (MHC) class I. We show that tapasin interacts with beta- and gamma-subunits of COPI coatomer. COPI retrieves membrane proteins from the Golgi network back to the endoplasmic reticulum (ER). The COPI subunit-associated tapasin also interacts with MHC class I molecules suggesting that tapasin acts as the cargo receptor for packing MHC class I molecules as cargo proteins into COPI-coated vesicles. In tapasin mutant cells, neither TAP nor MHC class I are detected in association with the COPI coatomer. Interestingly, tapasin-associated MHC class I molecules are antigenic peptide-receptive and detected in both the ER and the Golgi. Our data suggest that tapasin is required for the COPI vesicle-mediated retrograde transport of immature MHC class I molecules from the Golgi network to the ER.
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| 43. |
- Paulsson, Oskar, et al.
(författare)
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Attempted break-up of Rodinia at 850 Ma: geochronological evidence from the Seve-Kalak Superterrane, Scandinavian Caledonides
- 2002
-
Ingår i: Journal of the Geological Society. - 2041-479X. ; 159:6, s. 751-761
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Tidskriftsartikel (refereegranskat)abstract
- Lower thrust sheets of the Scandinavian Caledonides derive from the margin of Baltica, which was imbricated during Early Palaeozoic closure of oceans formed during separation of the Baltica, Laurentia and Siberia cratons. At Vistas (Kebnekaise Mts), the Seve Nappe Complex preserves rare lenses of a dolerite-intruded granite formed by anatexis during emplacement of gabbro into metasedimentary rocks. Ion microprobe U-Pb dating of prismatic zircons from the granite yielded an age of 845 +/- 14 Ma (mean square weighed deviation (MSWD) 1.15), interpreted to date magmatic crystallization. Cores of complex crystals indicate protolith ages of 1778 +/- 11 Ma (MSWD 0.86); one core yielded an Archaean age. From narrow rims, a 605 +/- 42 Ma metamorphic age is obtained, and is interpreted to reflect the emplacement of the extensive Vendian rift magmatic dolerite dyke swarm. The age pattern allows correlation with a previously dated magmatic complex within the equivalent Kalak Nappe Complex 300 km to the north. Bimodal magmatic complexes with this age pattern do not occur within the basement of the Caledonide foreland, nor elsewhere within the Baltic Shield. However, recent reinterpretations of the Knoydartian event in Scotland as rift related invites correlation with the West Highland Granite Gneiss, which intruded Moine metasedimentary rocks at c. 870 Ma. In Central Taimyr, 850-900 Ma granites of continental crustal derivation and with 1800-1900 Ma Sm-Nd model age occur associated with c. 740 Ma plagiogranites. Using recent palaeogeographical reconstructions, we interpret the evidence of 850-900 Ma magmatism, in Scandinavia, Scotland and Taimyr as bimodal rift magmatism in connected arms during an attempted break-up of Rodinia.
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| 44. |
- Paulsson Rokke, Hedvig, et al.
(författare)
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Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspected transthyretin amyloidosis
- 2020
-
Ingår i: Orphanet Journal of Rare Diseases. - : BioMed Central (BMC). - 1750-1172. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The diagnostic accuracy of histopathological detection of transthyretin amyloid (ATTR) by Congo red staining of abdominal fat samples has been questioned since low sensitivity has been reported, especially for patients with ATTR cardiomyopathy. However, the outcome of surgically obtained fat pad biopsies has not yet been evaluated. The aim was to evaluate the diagnostic accuracy of skin punch biopsies from abdominal fat in patients with suspected ATTR amyloidosis.Material and methods: Data were evaluated from patients who had undergone abdominal fat pad biopsies using a skin punch due to suspected amyloidosis from 2006 to 2015. The biopsies had been analysed using Congo red staining to determine the presence of amyloid, and immunohistochemistry or Western blot to determine the type of amyloidosis. The final diagnosis was based on the clinical picture, biopsy results and DNA sequencing. Minimum follow-up after the initial biopsy was 3 years.Results: Two hundred seventy-four patients (61% males) were identified, and in 132 (48%), a final diagnosis of amyloidosis had been settled. The majority (93%) had been diagnosed with hereditary transthyretin (ATTRv) amyloidosis, and therefore subsequent analyses were focused on these patients. Overall, our data showed a test specificity of 99% and a sensitivity of 91%. Ninety-eight (94%) of the patients had neuropathic symptoms at diagnosis, whereas 57 (55%) had signs of amyloid cardiomyopathy. Subgroup analyses showed that patients with merely neuropathic symptoms displayed the highest test sensitivity of 91%, whereas patients with pure cardiomyopathy displayed the lowest sensitivity of 83%. However, no significant differences in sensitivity were found between patients with or without cardiomyopathy or between the sexes.Conclusions: Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspect ATTRv amyloidosis, including patients presenting with cardiomyopathy. In addition, the method enables typing not only of the precursor protein but also of the amyloid fibril type, which is related to the phenotype and to the outcome of the disease.
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| 45. |
- Rykaczewska, Urszula, et al.
(författare)
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PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling
- 2020
-
Ingår i: Circulation Research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7330 .- 1524-4571. ; 126:5, s. 571-585
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens. Objective: Here, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall. Methods and Results: Genetic analyses revealed association of intronic PCSK6 variant rs1531817 with maximum internal carotid intima-media thickness progression in high-cardiovascular risk subjects. This variant was linked with PCSK6 mRNA expression in healthy aortas and plaques but also with overall plaque SMA+ cell content and pericyte fraction. Increased PCSK6 expression was found in several independent human cohorts comparing atherosclerotic lesions versus healthy arteries, using transcriptomic and proteomic datasets. By immunohistochemistry, PCSK6 was localized to fibrous cap SMA+ cells and neovessels in plaques. In human, rat, and mouse intimal hyperplasia, PCSK6 was expressed by proliferating SMA+ cells and upregulated after 5 days in rat carotid balloon injury model, with positive correlation to PDGFB (platelet-derived growth factor subunit B) and MMP (matrix metalloprotease) 2/MMP14. Here, PCSK6 was shown to colocalize and cointeract with MMP2/MMP14 by in situ proximity ligation assay. Microarrays of carotid arteries from Pcsk6(-/-) versus control mice revealed suppression of contractile SMC markers, extracellular matrix remodeling enzymes, and cytokines/receptors. Pcsk6(-/-) mice showed reduced intimal hyperplasia response upon carotid ligation in vivo, accompanied by decreased MMP14 activation and impaired SMC outgrowth from aortic rings ex vivo. PCSK6 silencing in human SMCs in vitro leads to downregulation of contractile markers and increase in MMP2 expression. Conversely, PCSK6 overexpression increased PDGFBB (platelet-derived growth factor BB)-induced cell proliferation and particularly migration. Conclusions: PCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling.
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| 46. |
- Sabater-Lleal, Maria, et al.
(författare)
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Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.
- 2014
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5×10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD.
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| 47. |
- Saito, Roy-Akira, et al.
(författare)
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Forkhead box F1 regulates tumor-promoting properties of cancer-associated fibroblasts in lung cancer.
- 2010
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Ingår i: Cancer research. - 1538-7445 .- 0008-5472. ; 70:7, s. 2644-54
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Tidskriftsartikel (refereegranskat)abstract
- Cancer-associated fibroblasts (CAF) attract increasing attention as potential cancer drug targets due to their ability to stimulate, for example, tumor growth, invasion, angiogenesis, and metastasis. However, the molecular mechanisms causing the tumor-promoting properties of CAFs remain poorly understood. Forkhead box F1 (FoxF1) is a mesenchymal target of hedgehog signaling, known to regulate mesenchymal-epithelial interactions during lung development. Studies with FoxF1 gain- and loss-of-function fibroblasts revealed that FoxF1 regulates the contractility of fibroblasts, their production of hepatocyte growth factor and fibroblast growth factor-2, and their stimulation of lung cancer cell migration. FoxF1 status of fibroblasts was also shown to control the ability of fibroblasts to stimulate xenografted tumor growth. FoxF1 was expressed in CAFs of human lung cancer and associated with activation of hedgehog signaling. These observations suggest that hedgehog-dependent FoxF1 is a clinically relevant lung CAF-inducing factor, and support experimentally the general concept that CAF properties can be induced by activation of developmentally important transcription factors.
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| 48. |
- Strell, Carina, et al.
(författare)
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Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:9, s. 983-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal-epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases. Methods: Stromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided. Results: PDGFR alpha((low))/PDGFR beta((high)) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype. Conclusions: A PDGFR alpha((low))/PDGFR beta((high)) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma-epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial-stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.
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| 49. |
- Sun, Jing, et al.
(författare)
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Utilizing BIM and GIS for Representation and Visualization of 3D Cadastre
- 2019
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Ingår i: ISPRS International Journal of Geo-Information. - : MDPI. - 2220-9964. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- The current three-dimensionally (3D) delimited property units are in most countries registered using two-dimensional (2D) documentation and textual descriptions. This approach has limitations if used for representing the actual extent of complicated 3D property units, in particular in city centers. 3D digital models such as building information model (BIM) and 3D geographic information system (GIS) could be utilized for accurate identification of property units, better representation of cadastral boundaries, and detailed visualization of complex buildings. To facilitate this, several requirements need to be identified considering organizational, legal, and technical aspects. In this study, we formulate these requirements and then develop a framework for integration of 3D cadastre and 3D digital models. The aim of this paper is that cadastral information stored based on the land administration domain model (LADM) are integrated with BIM on building level for accurate representation of legal boundaries and with GIS on city level for visualization of 3D cadastre in urban environments. The framework is implemented and evaluated against the requirements in a practical case study in Sweden. The conclusion is that the integration of the cadastral information and BIM/GIS is possible on both conceptual level and data level which will facilitate that organizations dealing with cadastral information (cadastral units), BIM models (architecture, engineering, and construction companies), and GIS (surveying units on e.g., municipality level) can exchange information; this facilitates better representation and visualization of 3D cadastral boundaries.
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| 50. |
- Torbrand, Christian, et al.
(författare)
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Pressure transduction to the thoracic cavity during topical negative pressure therapy of a sternotomy wound.
- 2008
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Ingår i: International Wound Journal. - 1742-481X. ; 5:4, s. 579-584
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Tidskriftsartikel (refereegranskat)abstract
- The present study was performed to examine pressure transduction to the thoracic cavity during topical negative pressure (TNP) therapy of a sternotomy wound. Seven pigs underwent median sternotomy. Pressure transduction catheters were placed on the anterior surface of the heart (under the foam), in the pericardium (under the heart), in the left pleura and in the oesophagus at the level of the heart. The wound was sealed as for TNP therapy. The vacuum source was set to deliver negative pressures between -50 and -200 mmHg. The pressure on the anterior surface of the heart changed in a linear relationship with the applied negative pressure and was slightly lower than the applied negative pressure (-102 +/- 9 mmHg at delivered -125 mmHg). Further down in the thoracic cavity, in the pericardium (under the heart), in the left pleura and in the oesophagus, the wound pressure was only slightly affected by TNP therapy. In conclusion during TNP therapy, negative pressure is effectively transmitted to anterior portions of the heart. This may explain our recent findings that TNP increases microvascular blood flow in the myocardium. The pressure difference between the anterior and the posterior portions of the heart causes the right ventricle to be sucked up towards the posterior parts of the sternum, where it might be exposed to the sharp edges of the sternal bone, which may result in heart injury.
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