| 1. |
- Lundgren, Fredrik, et al.
(författare)
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PTFE bypass to below-knee arteries : distal vein collar or not? A prospective randomised multicentre study
- 2010
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 39:6, s. 747-754
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study.MethodsPatients with critical limb ischaemia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups – bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first.ResultsIn the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%).At 3 years, primary patency was 26% (95% confidence interval (CI) 18–38) with a vein collar and 43 (33–58) without a vein collar for femoro-popliteal bypass and 20 (11–38), and 17 (9–33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54–75) and 61 (50–74) for femoro-popliteal bypass, and 59 (46–76) and 44 (32–61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan–Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage.ConclusionThis study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery.
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| 7. |
- Kuschmierz, Paul, et al.
(författare)
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European first-year university students accept evolution but lack substantial knowledge about it : A standardized European cross-country assessment
- 2021
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Ingår i: Evolution. - : BioMed Central (BMC). - 1936-6426 .- 1936-6434. ; 14:1, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Investigations of evolution knowledge and acceptance and their relation are central to evolution education research. Ambiguous results in this field of study demonstrate a variety of measuring issues, for instance differently theorized constructs, or a lack of standardized methods, especially for cross-country comparisons. In particular, meaningful comparisons across European countries, with their varying cultural backgrounds and education systems, are rare, often include only few countries, and lack standardization. To address these deficits, we conducted a standardized European survey, on 9200 first-year university students in 26 European countries utilizing a validated, comprehensive questionnaire, the “Evolution Education Questionnaire”, to assess evolution acceptance and knowledge, as well as influencing factors on evolution acceptance. Results: We found that, despite European countries’ different cultural backgrounds and education systems, European first-year university students generally accept evolution. At the same time, they lack substantial knowledge about it, even if they are enrolled in a biology-related study program. Additionally, we developed a multilevel-model that determines religious faith as the main influencing factor in accepting evolution. According to our model, knowledge about evolution and interest in biological topics also increase acceptance of evolution, but to a much lesser extent than religious faith. The effect of age and sex, as well as the country’s affiliation, students’ denomination, and whether or not a student is enrolled in a biology-related university program, is negligible. Conclusions: Our findings indicate that, despite all their differences, most of the European education systems for upper secondary education lead to acceptance of evolution at least in university students. It appears that, at least in this sample, the differences in knowledge between countries reflect neither the extent to which school curricula cover evolutionary biology nor the percentage of biology-related students in the country samples. Future studies should investigate the role of different European school curricula, identify particularly problematic or underrepresented evolutionary concepts in biology education, and analyze the role of religious faith when teaching evolution.
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| 11. |
- Gebreegziabher, Z., et al.
(författare)
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The distributive effect and food security implications of biofuels investment in Ethiopia: A CGE analysis
- 2018
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Ingår i: Agricultural Adaptation to Climate Change in Africa: Food Security in a Changing Environment. - New York, NY : RFF Press, 2018. : Taylor and Francis. - 9781351369510 - 9781138555976 ; , s. 252-282
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Bokkapitel (refereegranskat)abstract
- This chapter asks whether there will be positive or negative impacts on smallholder farmers and rural households as more agricultural land is used for biofuels production. The study uses a computable general equilibrium model to assess the distributive effects and food security implications of biofuels production in Ethiopia. We model the production of jatropha, castor bean, palm oil, and sugarcane as biofuel feedstock crops, with and without the effect of technology spillovers into food cereal crops. We find that the technology spillover effects of certain feedstock crops can increase the production of food cereals (with the effect varying across agro-ecological zones) without increasing cereal prices. In particular, when we model the production of sugarcane as a feedstock, and when we model jatropha and castor bean scenarios with spillover effects, production activities are projected to increase overall agriculture production and food security. When spillover effects are considered, biofuel investment tends to improve the welfare of most rural poor households. Urban households benefit from returns to labor under some scenarios. Thus, for both rural and urban households, biofuels expansion can improve household welfare under some scenarios. These findings assume that continued government investment in roads allows biofuels production to expand on land that is currently unutilized, so that smallholders do not lose land. © 2018 Environment for Development (EfD) Initiative.
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| 15. |
- Jadersten, M., et al.
(författare)
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Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 292:6, s. 925-940
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Tidskriftsartikel (refereegranskat)abstract
- Background Treatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1. Objectives In this phase 1 trial, we evaluated the feasibility, safety and efficacy of the addition of hydroxyurea to standard chemotherapy with cytarabine/daunorubicin in newly diagnosed AML patients. Methods Nine patients were enrolled and received at least two courses of ara-C (1 g/m(2)/2 h b.i.d. d1-5, i.e., a total of 10 g/m(2) per course), hydroxyurea (1-2 g d1-5) and daunorubicin (60 mg/m(2) d1-3). The primary endpoint was safety; secondary endpoints were complete remission rate and measurable residual disease (MRD). Additionally, pharmacokinetic studies of ara-CTP and ex vivo drug sensitivity assays were performed. Results The most common grade 3-4 toxicity was febrile neutropenia (100%). No unexpected toxicities were observed. Pharmacokinetic analyses showed a significant increase in median ara-CTP levels (1.5-fold; p = 0.04) in patients receiving doses of 1 g hydroxyurea. Ex vivo, diagnostic leukaemic bone marrow blasts from study patients were significantly sensitised to ara-C by a median factor of 2.1 (p = 0.0047). All nine patients (100%) achieved complete remission, and all eight (100%) with validated MRD measurements (flow cytometry or real-time quantitative polymerase chain reaction [RT-qPCR]) had an MRD level <0.1% after two cycles of chemotherapy. Treatment was well-tolerated, and median time to neutrophil recovery >1.0 x 10(9)/L and to platelet recovery >50 x 10(9)/L after the start of cycle 1 was 19 days and 22 days, respectively. Six of nine patients underwent allogeneic haematopoietic stem-cell transplantation (allo-HSCT). With a median follow-up of 18.0 (range 14.9-20.5) months, one patient with adverse risk not fit for HSCT experienced a relapse after 11.9 months but is now in second complete remission. Conclusion Targeted inhibition of SAMHD1 by the addition of hydroxyurea to conventional AML therapy is safe and appears efficacious within the limitations of the small phase 1 patient cohort. These results need to be corroborated in a larger study.
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| 16. |
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| 19. |
- Vesth, T., et al.
(författare)
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Veillonella, Firmicutes: Microbes disguised as Gram negatives
- 2013
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Ingår i: Standards in Genomic Sciences. - : Springer Science and Business Media LLC. - 1944-3277. ; 9:2, s. 431-448
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Tidskriftsartikel (refereegranskat)abstract
- The Firmicutes represent a major component of the intestinal microflora. The intestinal Firmicutes are a large, diverse group of organisms, many of which are poorly characterized due to their anaerobic growth requirements. Although most Firmicutes are Gram positive, members of the class Negativicutes, including the genus Veillonella, stain Gram negative. Veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerobes. In this work, the genomes of 24 Negativicutes, including eight Veillonella spp., are compared to 20 other Firmicutes genomes; a further 101 prokaryotic genomes were included, covering 26 phyla. Thus a total of 145 prokaryotic genomes were analyzed by various methods to investigate the apparent conflict of the Veillonella Gram stain and their taxonomic position within the Firmicutes. Comparison of the genome sequences confirms that the Negativicutes are distantly related to Clostridium spp., based on 16S rRNA, complete genomic DNA sequences, and a consensus tree based on conserved proteins. The genus Veillonella is relatively homogeneous: inter-genus pairwise comparison identifies at least 1,350 shared proteins, although less than half of these are found in any given Clostridium genome. Only 27 proteins are found conserved in all analyzed prokaryote genomes. Veillonella has distinct metabolic properties, and significant similarities to genomes of Proteobacteria are not detected, with the exception of a shared LPS biosynthesis pathway. The clade within the class Negativicutes to which the genus Veillonella belongs exhibits unique properties, most of which are in common with Gram-positives and some with Gram negatives. They are only distantly related to Clostridia, but are even less closely related to Gram-negative species. Though the Negativicutes stain Gram-negative and possess two membranes, the genome and proteome analysis presented here confirm their place within the (mainly) Gram positive phylum of the Firmicutes. Further studies are required to unveil the evolutionary history of the Veillonella and other Negativicutes.
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| 20. |
- Ahlström, A., et al.
(författare)
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No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture
- 2023
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 38:12, s. 2400-2411
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.
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| 30. |
- Bohlin, Leif, et al.
(författare)
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Cone-plate instrument for stress relaxation measurements
- 1980
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 73:1, s. 61-65
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Tidskriftsartikel (refereegranskat)abstract
- An instrument for the measurement of stress relaxation in shear is described. The force is detected by a sensitive piezoresistive pressure transducer. The requirement of constant strain can be fulfilled within less than 1%. Preset values of shear strain can be imposed on the sample within 0.1 sec. This instrument is suitable for soft solids and elastic liquids with a lower limit of ∼ 1 sec for the relaxation time. Results are given for wheat flour dough, a gelatinous deoxycholate complex and a gelatin gel. The instrument is simple, robust, and reliable, as well as inexpensive.
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| 31. |
- Bohlin, Markus, 1976-, et al.
(författare)
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Optimization of Railway Freight Shunting
- 2018
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Ingår i: Handbook of Optimization in the Railway Industry. - Cham : Springer-Verlag New York. ; , s. 181-212
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Bokkapitel (refereegranskat)abstract
- Railway freight shunting is the process of forming departing trains from arriving freight trains. The process is continuously performed at rail yards. The shunting procedure is complex and rail yards constitute bottlenecks in the rail freight network, often causing delays to individual shipments. One of the problems is that planning for the allocation of tracks at rail yards is difficult, given that the planner has limited resources (tracks, shunting engines, etc.) and needs to foresee the consequences of committed actions for the current inbound trains. The required schedules highly depend on the particular infrastructure of the rail yard, on the configuration of inbound and outbound trains, and on the business objectives. Thus, new optimization tools as active decision support for the dispatchers are closely tailored to the actual processes. Due to its practical relevance, a broad range of variants has been discussed and solved by the scientific community in recent years. For selected relevant variants, we describe their fruitful relation to scientific research topics such as graph coloring, sequence partitioning, and scheduling, we discuss their computational complexity and approximability, and we outline efficient optimization procedures. In particular, we consider a set of models and algorithms which are applicable in practice, and discuss their application to the shunting yards in Ludwigshafen, Germany and in Hallsberg, Sweden. We also discuss similarities and differences between the different approaches and outline the need for future research.
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| 32. |
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| 33. |
- Casper, C, et al.
(författare)
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Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes
- 2002
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 18:5, s. 343-352
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Tidskriftsartikel (refereegranskat)abstract
- Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n=2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4 1 cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children.
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| 34. |
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| 35. |
- Casper, CHE, et al.
(författare)
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Link between the X4 phenotype in human immunodeficiency virus type 1-infected mothers and their children, despite the early presence of R5 in the child
- 2002
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 186:7, s. 914-921
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Tidskriftsartikel (refereegranskat)abstract
- Coreceptor use was determined for human immunodeficiency virus type 1 (HIV-1) isolates of various subtypes from 11 women during pregnancy and their infected children. Isolates from peripheral blood mononuclear cells (n = 79) and from plasma (n = 59) were available. The clinical and immunological stages of HIV-1 infection were recorded. Coreceptor use was tested on human cell lines expressing CD4 and different chemokine receptors. The R5 virus predominated, and only 9 isolates from 2 mothers used CXC chemokine receptor 4. All children carried the R5 virus at the time of diagnosis of HIV-1 infection. In 2 children of mothers carrying the X4 virus, the virus switched from R5 to X4 or to R5X4 by age 18 months (child no. 9) and age 48 months (child no. 10), whereas no children followed up to a similar age whose mothers were carrying the R5 virus experienced such a switch (). This points to a link between the P = .048 presence of X4 virus in the mother and the emergence of X4 virus in her child.
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| 36. |
- Clevestig, P, et al.
(författare)
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The X4 phenotype of HIV type 1 evolves from R5 in two children of mothers, carrying X4, and is not linked to transmission
- 2005
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 21:5, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we found that emergence of the X4 viral phenotype in HIV-1-infected children was related to the presence of X4 in their mothers (C. H. Casper et al., J Infect Dis 2002; 186: 914-921). Here, we investigated the origin of the X4 phenotype in the child, analyzing two mother-child pairs (Ma-Ca, Mb-Cb) where the mothers carried X4 and their children developed X4 after an initial presence of R5. We used nested polymerase chain reaction of the env V3 region to generate 203 HIV-1 clones for sequencing (Ma, n = 44; Ca, n = 73; Mb, n = 61; Cb, n = 25) from DNA of peripheral blood mononuclear cell (PBMC) lysates, altogether 167 clones, or from cDNA of plasma RNA, 36 clones. PBMC and plasma isolate sequences from each time point enabled us to assign the probable phenotype to clone sequences in a phylogenetic tree. The transmission and evolution were reconstructed using the maximum likelihood method. In mother-child pair Ma-Ca, one maternal R5 isolate clustered with the child's R5 sequences, at the earliest time when R5 was isolated in the child, confirming this as a likely source of the transmitted R5 phenotype. At age 3, an X4 population was present in the child that had evolved from the child's own R5-associated population, clearly distinct from the maternal X4 sequences. The second mother-child pair (Mb-Cb) displayed a similar pattern. Amino acid substitution patterns corroborated the conclusions from the phylogenetic tree. Thus, in both children, the X4 virus developed from their own R5 population, and was not caused by transmission of X4.
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| 37. |
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| 41. |
- Engstrand, Thomas, et al.
(författare)
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Development of a bioactive implant for repair and potential healing of cranial defects
- 2014
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Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 120:1, s. 273-277
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Tidskriftsartikel (refereegranskat)abstract
- The repair of complex craniofacial bone defects is challenging and a successful result is dependent on the size of the defect, quality of the soft tissue covering the defect, and choice of reconstruction method. The objective of this study was to develop a bioactive cranial implant that could provide a permanent reconstructive solution to the patient by stimulating bone healing of the defect. In this paper the authors report on the feasibility and clinical results of using such a newly developed device for the repair of a large traumatic and therapy-resistant cranial bone defect. The patient had undergone numerous attempts at repair, in which established methods had been tried without success. A mosaic-designed device was manufactured and implanted, comprising interconnected ceramic tiles with a defined calcium phosphate composition. The clinical outcome 30 months after surgery revealed a restored cranial vault without postoperative complications. Computed tomography demonstrated signs of bone ingrowth. Examination with combined 18F-fluoride PET and CT provided further evidence of bone healing of the cranial defect.
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| 42. |
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| 43. |
- Gout, Thomas L., et al.
(författare)
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Diffusive processes in aqueous glass dissolution
- 2019
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Ingår i: npj Materials Degradation. - : Springer Science and Business Media LLC. - 2397-2106. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- High level nuclear waste is often immobilised in a borosilicate glass for disposal. However, this glass corrodes in contact with aqueous solutions. To predict radionuclide releases from wasteforms, their dissolution mechanisms must be understood. Understanding glass dissolution mechanisms presents a challenge across numerous other disciplines and many glass dissolution models still remain conflicted. Here we show that diffusion was a significant process during the later stages of dissolution of a simplified waste glass but was not evidenced during the initial stages of dissolution. The absence of measurable isotopic fractionation in solution initially supports models of congruent dissolution. However, the solution becoming isotopically lighter at later times evidences diffusive isotopic fractionation and opposes models that exclude diffusive transport as a significant mechanism. The periodically sampled isotopic methodologies outlined here provide an additional dimension with which to understand glass dissolution mechanisms beyond the usual measurement of solution concentrations and, post-process, nano-scale analysis of the altered glass.
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| 44. |
- Gout, Thomas L., et al.
(författare)
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Temperature dependent lithium isotope fractionation during glass dissolution
- 2021
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533. ; 313, s. 133-154
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the mechanisms by which borosilicate glasses corrode in contact with aqueous solutions remains a challenge to the safety case for the geological disposal of vitrified high-level nuclear waste. Here, lithium isotope fingerprinting techniques were applied to the leachates of a simulant Magnox waste glass to probe the mechanisms of aqueous corrosion at both short and long timescales (6 hours to 464 days). Experiments took place at 40 and 90 degrees C to assess the consistency of the dissolution mechanisms across a range of commonly employed temperatures and the legitimacy of applying higher temperature experimental datasets to understand glass corrosion within a disposal facility at lower temperatures. Two competing release mechanisms were observed for lithium (diffusion and hydrolysis), and the relative proportions of these mechanisms changed through time. Leachates initially had lower delta(7) Li values than the pristine glass (-2.7 parts per thousand at 40 degrees C and 1.1 parts per thousand at 90 degrees C relative to the pristine glass) at both temperatures due to lithium leaching incongruently through diffusive processes. The greater offset between solution and solid at lower temperatures indicates a larger rate of diffusion (incongruent dissolution) relative to the rate of hydrolysis (congruent dissolution) at lower temperatures. The fraction of lithium released through diffusion relative to the fraction of lithium released through hydrolysis then increased at both temperatures with time up to 126 days, increasing from 0.47 and 0.22 at 6 hours to 0.66 and 0.41 at 126 days at 40 and 90 degrees C respectively. Subsequently, the fractions of lithium released through diffusion sharply decreased to 0.36 at 40 degrees C and 0.22 at 90 degrees C after 464 days, consistent with network hydrolysis coupled with secondary phase precipitation later controlling the long-term release of Li at both temperatures. Throughout the duration of the experiments (464 days) the delta(7) Li values in solution increased to 9.0 parts per thousand at 40 degrees C and 10.0 parts per thousand at 90 degrees C due to the formation of talc and montmorillonite phases at 40 degrees C and additional smectite phases at 90 degrees C. Further, no evidence for the formation of a diffusive barrier to the transport of Li within the alteration layers became apparent during the later stages of dissolution at either temperature. However, the fraction of lithium leached through diffusion was still significant throughout all stages of dissolution. Lithium isotope ratios in solution were correlated with the transition from a system which was increasingly dominated by lithium diffusion as the dissolution rate slowed to one which was controlled by hydrolysis coupled with secondary phase precipitation at long durations. Alongside elemental ratios in solution, these results were consistent with the same set of mechanisms governing dissolution across the temperature range studied.
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| 45. |
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| 46. |
- Hedner, E., et al.
(författare)
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Brominated cyclodipeptides from the marine sponge Geodia barretti as selective 5-HT ligands
- 2006
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 69:10, s. 1421-1424
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Tidskriftsartikel (refereegranskat)abstract
- The brominated cyclodipeptides barettin(cyclo[(6-bromo-8-entryptophan) arginine]) and 8,9-dihydrobarettin ( cyclo[(6-bromotryptophan) arginine]) isolated from the marine sponge Geodia barretti have previously been shown to inhibit settlement of barnacle larvae in a dose-dependent manner in concentrations ranging from 0.5 to 25 mu M. To further establish the molecular target and mode of action of these compounds, we investigated their affinity to human serotonin receptors. The tryptophan residue in the barettins resembles that of endogenous serotonin [5-hydroxytryptamine]. A selection of human serotonin receptors, including representatives from all subfamilies (1-7), were transfected into HEK-293 cells. Barettin selectively interacted with the serotonin receptors 5-HT2A, 5-HT2C, and 5-HT4 at concentrations close to that of endogenous serotonin, with the corresponding K-i values being 1.93, 0.34, and 1.91 mu M, respectively. 8,9-Dihydrobarettin interacted exclusively with the 5-HT2C receptor with a K-i value of 4.63 mu M; it failed to show affinity to 5-HT2A and 5-HT4, indicating that the double bond between the tryptophan and arginine residue plays an important role in the interaction with the receptor proteins.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Huss, U, et al.
(författare)
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Screening of ubiquitous plant constituents for COX-2 inhibition with a scintillation proximity based assay
- 2002
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 65:11, s. 1517-1521
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Tidskriftsartikel (refereegranskat)abstract
- A rapid semi-homogeneous cyclooxygenase-2 (COX-2) enzymatic assay using scintillation proximity assay (SPA) technology was developed, and 49 ubiquitous plant secondary metabolites were screened for inhibition of COX-2-catalyzed prostaglandin E(2) (PGE(2)) biosynthesis. Assay conditions were optimized with respect to reaction time, amount of antibody, radiolabeled PGE(2), and SPA beads, and the kinetic parameter, K(m), was estimated. The assay was validated with two natural triterpenoids, ursolic and oleanolic acid, known to inhibit COX-2, as well as with four synthetic COX inhibitors, NS-398, rofecoxib, indomethacin, and aspirin. Plant metabolites of different biosynthetic origin representing several substance classes, including alkaloids, anthraquinones, flavonoids, phenylpropanes, steroids, and terpenes, were screened for inhibition of COX-2-catalyzed PGE(2) production. Of these 49 plant metabolites, eugenol, pyrogallol, and cinnamaldehyde (with IC(50) values of 129, 144, and 245 microM, respectively) were found to inhibit COX-2. This study showed that a COX-2-catalyzed PGE(2) assay using SPA is suitable for screening natural compounds with respect to COX-2 inhibition.
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