| 1. |
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| 2. |
- Costa, Thales H.F., et al.
(författare)
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Demonstration-scale enzymatic saccharification of sulfite-pulped spruce with addition of hydrogen peroxide for LPMO activation
- 2020
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Ingår i: Biofuels, Bioproducts and Biorefining. - : Wiley. - 1932-104X .- 1932-1031. ; 14:4, s. 734-745
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Tidskriftsartikel (refereegranskat)abstract
- The saccharification of lignocellulosic materials like Norway spruce is challenging due to the recalcitrant nature of the biomass, and it requires optimized and efficient pretreatment and enzymatic hydrolysis processes to make it industrially feasible. In this study, we report successful enzymatic saccharification of sulfite-pulped spruce (Borregaard's BALI™ process) at demonstration scale, achieved through the controlled delivery of hydrogen peroxide (H2O2) for the activation of lytic polysaccharide monooxygenases (LPMOs) present in the cellulolytic enzyme preparation. We achieved 85% saccharification yield in 4 days using industrially relevant conditions – that is, an enzyme dose of 4% (w/w dry matter of substrate) of the commercial cellulase cocktail Cellic CTec3 and a substrate loading of 12% (w/w). Addition of H2O2 and the resulting controlled and high LPMO activity had a positive effect on the rate of saccharification and the final sugar titer. Clearly, the high LPMO activity was dependent on feeding the reactors with the LPMO co-substrate H2O2, as in situ generation of H2O2 from molecular oxygen was limited. These demonstration-scale experiments provide a solid basis for the use of H2O2 to improve enzymatic saccharification of lignocellulosic biomass at large industrial scale.
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| 3. |
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| 4. |
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| 5. |
- Mandenius, C. F., et al.
(författare)
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Predicting fermentability of wood hydrolyzates with responses from electronic noses
- 1999
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Ingår i: Biotechnology progress (Print). - New York, NY, United States : AIChE. - 8756-7938 .- 1520-6033. ; 15:4, s. 617-621
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Tidskriftsartikel (refereegranskat)abstract
- The fermentability of lignocellulose hydrolyzates have been predicted from the responses of a combination of chemical gas sensors. The hydrolyzates were prepared by dilute-acid hydrolysis of wood from pine, aspen, birch, and spruce. The volatile emission from the hydrolyzates before fermentation was measured, and the sensor array response pattern was compared with the observed fermentability of the hydrolyzates, i.e. with the final ethanol concentration after fermentation and the maximum specific ethanol production rate. Two concentration parameters in the hydrolyzates, furfural and the sum of furfural and 5-(hydroxymethyl)furfural (HMF), were also predicted from the responses. The sensors used were metal oxide semiconductor field effect transistors (MOSFET), tin oxide semiconductor devices, and conductive polymer sensors configured in two sensor arrays. The sensor array response pattern was analyzed by principal component analysis and artificial neural networks. Predictions from artificial neural networks deviated from measured values with less than 15%.The fermentability of lignocellulose hydrolyzates have been predicted from the responses of a combination of chemical gas sensors. The hydrolyzates were prepared by dilute-acid hydrolysis of wood from pine, aspen, birch, and spruce. The volatile emission from the hydrolyzates before fermentation was measured, and the sensor array response pattern was compared with the observed fermentability of the hydrolyzates, i.e. with the final ethanol concentration after fermentation and the maximum specific ethanol production rate. Two concentration parameters in the hydrolyzates, furfural and the sum of furfural and 5-(hydroxymethyl)furfural (HMF), were also predicted from the responses. The sensors used were metal oxide semiconductor field effect transistors (MOSFET), tin oxide semiconductor devices, and conductive polymer sensors configured in two sensor arrays. The sensor array response pattern was analyzed by principal component analysis and artificial neural networks. Predictions from artificial neural networks deviated from measured values with less than 15%.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 11. |
- Carrasco, Cristhian, et al.
(författare)
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Arabinosylated phenolics obtained from SO2-steam-pretreated sugarcane bagasse
- 2012
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Ingår i: Journal of Chemical Technology and Biotechnology. - : Wiley. - 0268-2575. ; 87:12, s. 1723-1726
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Tidskriftsartikel (refereegranskat)abstract
- A pentose-rich hydrolysate fraction obtained by extraction of steam-pretreated sugarcane bagasse was analysed with regard to dissolved phenolics. The liquid obtained after steam pretreatment (2% SO2 (w/w) at 190 degrees C for 5 min) was divided into two parts: one containing dissolved compounds originating from hemicellulose (with xylose as the dominating compound), and the other containing predominantly dissolved compounds originating from lignin. Using nuclear magnetic resonance, the main dissolved compounds originating from lignin were identified as the glycosylated aromatics, 5-O-(trans-feruloyl)-L-Arabinofuranose and 5-O-(trans-coumaroyl)-L-Arabinofuranose, together with p-coumaric acid and small amounts of more common free phenolics such as p-hydroxybenzaldehyde, p-hydroxybenzoic acid and vanillin. The phenolic compounds were analysed and quantified using reversed-phase high-performance liquid chromatography. The findings show that SO2 steam explosion opened up new degradation pathways during lignin degradation. Copyright (c) 2012 Society of Chemical Industry
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| 12. |
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| 13. |
- Dellborg, Mikael, 1954, et al.
(författare)
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Adults With Congenital Heart Disease: Trends in Event-Free Survival Past Middle Age
- 2023
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 147:12, s. 930-938
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Tidskriftsartikel (refereegranskat)abstract
- Background:The survival of children with congenital heart disease has increased substantially over the past decades, with 97% currently reaching adulthood. The total effect of advanced treatment on future mortality and morbidity in adult survivors with congenital heart disease (CHD) is less well described. Methods:We used data from the Swedish National Inpatient, Outpatient, and Cause of Death Register to identify patients with CHD who were born between 1950 and 1999 and were alive at 18 years of age. Ten controls identified from the Total Population Register were matched for year of birth and sex and with each patient with CHD. Follow-up was from 1968 and 18 years of age until death or at the end of the study (2017). Survival percentage with 95% CI for all-cause mortality were performed with Kaplan-Meier survival function. Cox proportional hazard regression models with hazard ratios (HRs) and 95% CI were used to estimate the risk of all-cause mortality. Results:We included 37 278 patients with adult CHD (ACHD) and 412 799 controls. Mean follow-up was 19.2 years (+/- 13.6). Altogether, 1937 patients with ACHD (5.2%) and 6690 controls (1.6%) died, a death rate of 2.73 per 1000 person-years and 0.84 per 1000 person years, respectively. Mortality was 3.2 times higher (95% CI, 3.0-3.4; P<0.001) among patients with ACHD compared with matched controls. Up to the maximum of 50 years of follow-up, >75% of patients with ACHD were still alive. Mortality was highest among patients with conotruncal defects (HR, 10.13 [95% CI, 8.78-11.69]), but also significantly higher for the more benign lesions, with the lowest risk in patients with atrial septal defects (HR, 1.36 [95% CI, 1.19-1.55]). At least 75% of patients with ACHD alive at 18 years of age lived past middle age and became sexagenerians. Conclusions:In this large, nationwide, register-based cohort study of patients with ACHD surviving to 18 years of age, the risk of mortality up to 68 years of age was >3 times higher compared with matched controls without ACHD. Despite this, at least 75% of patients with CHD alive at 18 years of age lived past middle age and became sexagenerians. A notable risk decline in the mortality for patients with ACHD was seen for those born after 1975.
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| 14. |
- Doria Medina, Roberto, et al.
(författare)
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fMRI after Phalloplasty with Nerve Anastomosis in a Trans-Man Patient
- 2017
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Ingår i: Plastic and Reconstructive Surgery-Global Open. - : Ovid Technologies (Wolters Kluwer Health). - 2169-7574. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- We report on a case of a trans-man patient, who underwent penile reconstruction with the use of a radial forearm flap, urethroplasty, vaginectomy and scrotoplasty, insertion of testicle implants, and penile erection implants, similar to previously described methods. One of the requirements for an ideal phalloplasty is the preservation of erogenous sensitivity, which is often demanded by the patients for fulfilling their sexual well-being. For the first time known to us, we use a functional magnetic resonance imaging following radial forearm flap phalloplasty with nerve anastomosis to assess the cortical activation after clitoral stimulation. The patient was poked with a plastic pen on the neophallus and the groin. Regular block design with T1 and BOLD-T2* images were used. The results contradict the classic Penfield and Rasmussen homunculus, that is, the activations in the primary somatosensory cortex (S1) were bilateral with a left-sided dominance in the lateral parts of the medial postcentral gyrus (same region as the groin), and no activations were observed in the mesial parts of the postcentral gyrus. We also reported bilateral activations with a left-sided dominance in the secondary somatosensory cortex (S2) and near Broca's area at the sylvian fissure just posterior to ramus ascendens. Our findings are similar to previous studies reporting on imaging related to genital sensitivity.
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| 15. |
- DORING, J, et al.
(författare)
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HIGH-LYING 3-QUASI-PARTICLE BANDS AND SIGNATURE SPLITTING IN RB-81
- 1994
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 50:4, s. 1845-1850
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Tidskriftsartikel (refereegranskat)abstract
- Two new high-lying level sequences of negative parity have been identified in the odd-proton nucleus Rb-81 by in-beam gamma-ray spectroscopy using the reactions Br-79(alpha, 2n) at 27 MeV and Zn-68(F-19, alpha2n) at 72 MeV. One sequence, dominated by M1 transitions, is interpreted as a three-quasiparticle band predominantly containing a neutron in the p1/2, p3/2, or f5/2 subshell coupled to g9/2 proton and g9/2 neutron excitations. The other new level sequence forms the three-quasiparticle extension of the unfavored negative-parity band, but the states decay also by E1 transitions. The signature splitting points to a configuration where an aligned g9/2 proton pair is involved.
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| 16. |
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| 17. |
- Kadić, Adnan, et al.
(författare)
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In situ measurements of oxidation–reduction potential and hydrogen peroxide concentration as tools for revealing LPMO inactivation during enzymatic saccharification of cellulose
- 2021
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Biochemical conversion of lignocellulosic biomass to simple sugars at commercial scale is hampered by the high cost of saccharifying enzymes. Lytic polysaccharide monooxygenases (LPMOs) may hold the key to overcome economic barriers. Recent studies have shown that controlled activation of LPMOs by a continuous H2O2 supply can boost saccharification yields, while overdosing H2O2 may lead to enzyme inactivation and reduce overall sugar yields. While following LPMO action by ex situ analysis of LPMO products confirms enzyme inactivation, currently no preventive measures are available to intervene before complete inactivation. Results: Here, we carried out enzymatic saccharification of the model cellulose Avicel with an LPMO-containing enzyme preparation (Cellic CTec3) and H2O2 feed at 1 L bioreactor scale and followed the oxidation–reduction potential and H2O2 concentration in situ with corresponding electrode probes. The rate of oxidation of the reductant as well as the estimation of the amount of H2O2 consumed by LPMOs indicate that, in addition to oxidative depolymerization of cellulose, LPMOs consume H2O2 in a futile non-catalytic cycle, and that inactivation of LPMOs happens gradually and starts long before the accumulation of LPMO-generated oxidative products comes to a halt. Conclusion: Our results indicate that, in this model system, the collapse of the LPMO-catalyzed reaction may be predicted by the rate of oxidation of the reductant, the accumulation of H2O2 in the reactor or, indirectly, by a clear increase in the oxidation–reduction potential. Being able to monitor the state of the LPMO activity in situ may help maximizing the benefit of LPMO action during saccharification. Overcoming enzyme inactivation could allow improving overall saccharification yields beyond the state of the art while lowering LPMO and, potentially, cellulase loads, both of which would have beneficial consequences on process economics.
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| 18. |
- Kadić, A., et al.
(författare)
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Oxidation-reduction potential (ORP) as a tool for process monitoring of H2O2/LPMO assisted enzymatic hydrolysis of cellulose
- 2019
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Ingår i: Process Biochemistry. - : Elsevier BV. - 1359-5113. ; 86, s. 89-97
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Tidskriftsartikel (refereegranskat)abstract
- Oxidation-reduction potential (ORP) is an environmental factor of importance in several biological conversion processes. Lytic polysaccharide monooxygenases (LPMOs) catalyze oxidative disruption of the cellulose chain in the presence of oxygen or hydrogen peroxide and increase enzymatic hydrolysis yields. However, the enzymes are also sensitive to oxidative damage and the level of oxidative agent needs to be controlled to avoid inactivation of the LPMOs. In the current study, enzymatic hydrolysis of sulfite-pretreated softwood (12% DM loading) was carried out in lab scale reactors with gradual addition of hydrogen peroxide using an LPMO-containing commercial enzyme cocktail. The ORP was measured during enzymatic hydrolysis together with released glucose and the level of C4-oxidized dimer as a marker for LPMO activity. Arrests in LPMO activity coincided with a markedly changed ORP signal and this was utilized in subsequent experiments in which the feed rate of hydrogen peroxide was controlled by keeping the ORP at predetermined set-points of -40 mV, -80 mV and -120 mV. Under anaerobic conditions, the highest hydrolysis yield (78% after 72 h) was found for the ORP set-point of -80 mV. The results show that ORP can serve as an indicator of LPMO activity and may help optimizing overall process efficiency.
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| 19. |
- Kownacki, J, et al.
(författare)
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High-spin studies of the neutron deficient nuclei In-103, In-105, In-107, and In-109
- 1997
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Ingår i: Nuclear Physics A. - 0375-9474 .- 1873-1554. ; 627:2, s. 239-258
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states of the isotopes 103,105,107,109In have been investigated using in-beam γ-ray spectroscopic methods. Results from three different experiments are presented. Targets of 54Fe, 50Cr, and 92Mo were bombarded by a 270 and 261 MeV 58Ni beam and by a 95 MeV 19F beam, respectively. Reaction channel separation was achieved with a charged-particle detector array and in the first two experiments also with a 1π neutron detector system. As a result of these experiments the level schemes of 103,105,107,109In were significantly extended. Excited states of these odd-A indium isotopes are discussed within the framework of the nuclear shell model and the hole-core coupling scheme. The systematics of excited states of light odd-A indium isotopes is also discussed.
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| 20. |
- Lidén, H., et al.
(författare)
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On-line determination of non-volatile or low-concentration metabolites in a yeast cultivation using an electronic nose
- 2000
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Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 125:6, s. 1123-1128
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Tidskriftsartikel (refereegranskat)abstract
- An electronic nose was used for on-line gas phase monitoring of key metabolites in a Saccharomyces cerevisiae cultivation. The metabolites were either non-volatile or present at very low concentrations and therefore not detectable in the gas phase by the sensors in the electronic nose. It was found that it is still possible to make a prediction based on the off-gas emission. Artificial neural networks (ANNs) were trained using data acquired by the gas sensors and reference data obtained from on-line HPLC analyses, from a total of six cultivations to estimate concentrations of the metabolites glucose, glycerol, acetate and acetaldehyde. The ANNs were subsequently validated on an independent set of cultivation data resulting in a prediction accuracy described by the root mean square error (RMSE) of 0.13 (in the range 0-7.33), 0.015 (0.08-0.15), 0.012 (0-0.20) and 0.004 (0-0.11) g L-1, respectively. Data from a cultivation with higher initial glucose concentration were added to the original data and the extended set was used for training an ANN to determine concentration variables at higher concentration ranges than in the first study. The RMSE was 1.2 (0-9.31), 0.016 (0.09-0.20), 0.026 (0-0.19) and 0.010 (0-0.15) g L-1, respectively, when validating the ANNs.
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| 21. |
- Liden, H, 1971, et al.
(författare)
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Temporary circulatory support with extra corporeal membrane oxygenation in adults with refractory cardiogenic shock.
- 2009
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 43:4, s. 226-32
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Early and long-term survival in patients suffering from cardiogenic shock is poor. Treatment with mechanical assist devices is complicated and expensive but claim to improve survival. We reviewed our experience of venoarterial extracorporeal membrane oxygenation (ECMO) in patients with acute cardiogenic shock. DESIGN: ECMO was used in 52 patients with cardiogenic shock. They were divided into those not operated upon previously (n=19) and those having had cardiac surgery prior to circulatory collapse (n=33). RESULTS: Twenty-six patients were weaned from ECMO. Early mortality for all patients was 48%. Mortality beyond 30 days was 5.8%, with no mortality in the non-cardiotomy group. Long-term survival for patients in the non-cardiotomy group was 63%, as compared to 33% in post-cardiotomy patients (p=0.07). Age over 55 years, female gender or cannulation site did not appear to influence survival. CONCLUSION: Mortality for patients in cardiogenic shock is very high. Treatment with ECMO in patients with refractory cardiogenic shock can be performed with good survival especially in non-surgical patients.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Rodríguez-Varela, Ricardo, et al.
(författare)
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The genetic history of Scandinavia from the Roman Iron Age to the present
- 2023
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 186:1, s. 32-46
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Tidskriftsartikel (refereegranskat)abstract
- We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier.
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| 26. |
- Sten, S., et al.
(författare)
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Erik den heliges skelett
- 2016
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Ingår i: Fornvännen. - 0015-7813. ; 111:1, s. 27-40
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Tidskriftsartikel (refereegranskat)abstract
- No contemporary sources mention Erik Jedvardsson, Sweden's king saint. The only account of his life is the saint's legend, in its preserved form written in the late 13th century, and legends are notoriously untrustworthy. It says that in 1160, in the tenth year of Erik's reign, he was killed by a throne claimant. His remains have rested in a reliquary in Uppsala Cathedral since 1257 at the latest and survived the Reformation. A thorough investigation was made in 1946, and the development of new methods motivated a new investigation in 2014. 23 bones remain that apparently belong to the same individual. (They are accompanied in the reliquary by an unrelated shinbone.) Radiocarbon values are consistent with a death in 1160. The bones belong to a man, 35-40 years old, about 171 cm tall, without any discernible medical conditions. Bone density indicates a life of good nourishment and abundant exercise. The skull has one or two healed wounds that may have been due to weapons. Isotope analysis points to a diet rich in freshwater fish. Stable isotopes also imply that he did not spend his last decade in the expected Uppsala area but rather in Västergötland further south. Insufficient reference materials however make this a very preliminary conclusion. Samples for DNA analysis were collected, but the results are not expected for another year. The saint's legend says that in the king's final battle, the enemy swarmed him, and when he fell to the ground they gave him wound after wound until he lay half dead. They then taunted him and finally cut off his head. The remaining bones have at least nine cuts inflicted in connection with death, seven of them on the legs. No wounds have been found on the ribs or the remaining arm bone, which probably means that the king wore a hauberk but had less protected legs. Both shin bones have cuts inflicted from the direction of the feet, indicating that the victim lay on his front. A neck vertebra has been cut through, which could not have been done without removing the hau berk, i.e. not during battle. This confirms that there was an interlude, as described by the taunting in the legend, between battle and decapitation. At no point do the documented wounds gainsay the account of the fight given by the much later legend.
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| 27. |
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| 28. |
- Vilà C., Leonard J.A., Götherstöm A., Marklund S., Sandberg K., Lidén K., Wayne R.K., Ellegren H.
(författare)
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Widespread origins of domestic horse lineages
- 2001
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Ingår i: Science. ; 291, s. 474-477
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Tidskriftsartikel (refereegranskat)
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| 29. |
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| 30. |
- Webb, Emily C., et al.
(författare)
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Compound-specific amino acid isotopic proxies for detecting freshwater resource consumption
- 2015
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 63, s. 104-114
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Tidskriftsartikel (refereegranskat)abstract
- Of central importance to palaeodietary reconstruction is a clear understanding of relative contributions of different terrestrial (i.e., C3 vs. C4 plants) and aquatic (i.e., freshwater vs. marine) resources to human diet. There are, however, significant limitations associated with the ability to reconstruct palaeodiet using bulk collagen stable isotope compositions in regions where diverse dietary resources are available. Recent research has determined that carbon-isotope analysis of individual amino acids has considerable potential to elucidate dietary protein source where bulk isotopic compositions cannot. Using δ13CAA values for human and faunal remains from Zvejnieki, Latvia (8th – 3rd millennia BCE), we test several isotopic proxies focused on distinguishing freshwater protein consumption from both plant-derived and marine protein consumption. We determined that the Δ13CGly-Phe and Δ13CVal-Phe proxies can effectively discriminate between terrestrial and aquatic resource consumption, and the relationship between essential δ13CAA values and the Δ13CGly-Phe and Δ13CVal-Phe proxies can differentiate among the four protein consumption groups tested here. Compound-specific amino acid carbon-isotope dietary proxies thus enable an enhanced understanding of diet and resource exploitation in the past, and can elucidate complex dietary behaviour.
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| 31. |
- Webb, Emily C., et al.
(författare)
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Compound-specific amino acid isotopic proxies for distinguishing between terrestrial and aquatic resource consumption
- 2018
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Ingår i: Archaeological and Anthropological Sciences. - : Springer Science and Business Media LLC. - 1866-9557 .- 1866-9565. ; 10:1, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- Compound-specific amino acid carbon-isotope compositions have shown particular promise for elucidating dietary behaviors in complex environmental contexts, and may also be able to mitigate the effect of many of the limitations inherent to palaeodietary reconstructions. Here, we investigate the efficacy of compound-specific amino acid isotopic proxies in characterizing the consumption of different dietary protein sources using amino acid carbon-isotope compositions for humans and fauna from Rössberga (Early to Middle Neolithic), Köpingsvik (Mesolithic and Middle Neolithic), and Visby (Medieval Period), Sweden. We also assess the explanatory capabilities of an isotopic mixing model when used with essential amino acid carbon-isotope compositions of humans and local fauna. All three isotopic proxies distinguished among humans from the three sites consistently and informatively, and were able to enhance the broad interpretations made using bulk isotopic compositions. The mixing model palaeodietary reconstruction revealed considerable diversity in relative protein source contributions among individuals at both Köpingsvik and Visby. Comparing the mixing model for bulk carbon- and nitrogen-isotope compositions to the model for essential amino acid isotopic compositions further demonstrated the likelihood of underestimation and overestimation of marine protein consumption for both aquatic-dominant and mixed marine-terrestrial diets when using bulk isotopic compositions.
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| 32. |
- Zeraatkar, Amin, et al.
(författare)
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Rediscovery of Dionysia bachtiarica (Primulaceae) in Kuh-e Kallar after 119 years
- 2023
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Ingår i: The Iranian Journal of Botany. - 1029-788X. ; 29:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Botanical exploration in 2022 in the province of Chaharmahal and Bakhtiari, resulted in the collection of Dionysia bachtiarica, a narrow endemic species first collected in 1902 and described in 1905. This species has not been seen since 1903. Some morphological features were incompletely recorded, absent, or untrustworthy in earlier descriptions, due to limited herbarium material. In this study, new morphological data are provided based on analysis of live flowering and fruiting material, illustrated with photographs of the plant and its habitat, as well as line drawings. A full description of the species, its ecology, and phenology, as well as a key to all purple-flowered species in the Zagros Mountains, are provided. The possible relations of this enigmatic species are discussed. Due to its extremely limited known area of occurrence and a small number of individuals, it is considered to be Critically Endangered.
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| 33. |
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| 34. |
- Öst, Anita, 1965-, et al.
(författare)
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Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes
- 2007
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 21:13, s. 3696-3704
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Tidskriftsartikel (refereegranskat)abstract
- Reduced sensitivity to insulin in adipose, muscle, and liver tissues is a hallmark of type 2 diabetes. Animal models and patients with type 2 diabetes exhibit elevated levels of circulating retinol-binding protein (RBP4), and RBP4 can induce insulin resistance in mice. However, little is known about how RBP4 affects insulin signaling. We examined the mechanisms of action of RBP4 in primary human adipocytes. RBP4-treated adipocytes exhibited the same molecular defects in insulin signaling, via IRS1 to MAP kinase, as in adipocytes from patients with type 2 diabetes. Without affecting autophosphorylation of the insulin receptor, RBP4 blocked the insulin-stimulated phosphorylation of IRS1 at serine (307) [corresponding to serine (302) in the murine sequence] and concomitantly increased the EC50 (from 0.5 to 2 nM) for insulin stimulation of IRS1 phosphorylation at tyrosine. The phosphorylation of IRS1 at serine (312) [corresponding to serine (307) in the murine sequence] was not affected in cells from diabetic patients and was also not affected by RBP4. The EC50 for insulin stimulation of downstream phosphorylation of MAP kinase ERK1/2 was increased (from 0.2 to 0.8 nM) by RBP4. We show that ERK1/2 phosphorylation is similarly impaired in adipocytes from patients with type 2 diabetes. However, the sensitivity to insulin for downstream signaling to control of protein kinase B and glucose uptake was not affected by RBP4. When insulin-resistant adipocytes from patients with type 2 diabetes were incubated with antibodies against RBP4, insulin-induced phosphorylation of IRS1 at serine (307) was normalized and the EC50 for insulin stimulation of ERK1/2 phosphorylation was reduced. Endogenous levels of RBP4 were markedly reduced in adipocytes from obese or type 2 diabetic subjects, whereas expression levels of RBP4 mRNA were unaffected. These findings indicate that RBP4 may be released from diabetic adipocytes and act locally to inhibit phosphorylation of IRS1 at serine (307), a phosphorylation site that may integrate nutrient sensing with insulin signaling.
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