| 1. |
- Botling, Johan, et al.
(författare)
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Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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| 2. |
- Allamani, Allaman, et al.
(författare)
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Contextual Determinants of Alcohol Consumption Changes and Preventive Alcohol Policies : A 12-Country European Study in Progress 2011
- 2011
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Ingår i: Substance Use & Misuse. - : Informa UK Limited. - 1082-6084 .- 1532-2491. ; 46:10, s. 1288-1303
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Tidskriftsartikel (refereegranskat)abstract
- Beginning with France in the 1950s, alcohol consumption has decreased in Southern European countries with few or no preventive alcohol policy measures being implemented, while alcohol consumption has been increasing in Northern European countries where historically more restrictive alcohol control policies were in place, even though more recently they were loosened. At the same time, Central and Eastern Europe have shown an intermediate behavior. We propose that country-specific changes in alcohol consumption between 1960 and 2008 are explained by a combination of a number of factors: (1) preventive alcohol policies and (2) social, cultural, economic, and demographic determinants. This article describes the methodology of a research study designed to understand the complex interactions that have occurred throughout Europe over the past five decades. These include changes in alcohol consumption, drinking patterns and alcohol-related harm, and the actual determinants of such changes
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| 3. |
- Almstedt, Åsa, 1977-, et al.
(författare)
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Beyond Post-productivism : From Rural Policy Discource to Rural Diversity
- 2014
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Ingår i: European Countryside. - Berlin : Walter de Gruyter GmbH. - 1803-8417. ; 6:4, s. 297-306
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Tidskriftsartikel (refereegranskat)abstract
- There has been a strong discourse in public policy aimed at transforming rural places from venues of primary production into truly diverse socioeconomic landscapes. Yet conceptualisations of the rural as envisioned in the policy and politics of the ‘new economy’ often prove to be elusive on the ground. However, post-productive activity in rural areas has become a major focus for rural studies scholars. This paper investigates the ideas of post-productivism in the existing literature, and argues for a holistic understanding of post-productivism as an idea and political ambition rather than an imperative and irreversible change of rural economic activity. The purpose of the study is to make clear the division between post-productivism and the related concepts of post-production and post-productive activities in order to better understand processes of rural change in relation to different geographical contexts. It is argued that post-productivism as a concept stands apart from de facto post-production and alternative concepts such as multifunctionality and should be regarded as part of broader regional development discourses. The paper outlines several important fields in which post-productivism is a necessary component for rural transformation and development. While it is not always easily captured in indicators or empirical studies in rural locations, post- productivism exists at the level of discourse and planning and thus has real effects on the ground. The paper concludes by offering suggestions on how to apply the concepts of post-productivism, post-production and multifunctionality in future studies.
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| 4. |
- Berger, Karin, et al.
(författare)
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Cereal Byproducts Have Prebiotic Potential in Mice Fed a High-Fat Diet
- 2014
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 62:32, s. 8169-8178
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Tidskriftsartikel (refereegranskat)abstract
- Barley husks, rye bran, and a fiber residue from oat milk production were processed by heat pretreatment, various separation steps, and treatment with an endoxylanase in order to improve the prebiotic potential of these cereal byproducts. Metabolic functions were intended to improve along with improved microbial activity. The products obtained were included in a high-fat mouse diet so that all diets contained 5% dietary fiber. In addition, high-fat and low-fat controls as well as partially hydrolyzed guar gum were included in the study. The soluble fiber product obtained from rye bran caused a significant increase in the bifidobacteria (log copies of 16S rRNA genes; median (25−75 percentile): 6.38 (6.04−6.66) and 7.47 (7.30−7.74), respectively; p < 0.001) in parallel with a tendency of increased production of propionic acid and indications of improved metabolic function compared with high-fat fed control mice. The oat-derived product caused an increase in the pool of cecal propionic (from 0.62 ± 0.12 to 0.94 ± 0.08) and butyric acid (from 0.38 ± 0.04 to 0.60 ± 0.04) compared with the high-fat control, and it caused a significant increase in lactobacilli (log copies of 16S rRNA genes; median (25−75 percentile): 6.83 (6.65−7.53) and 8.04 (7.86−8.33), respectively; p < 0.01) in the cecal mucosa. However, no changes in measured metabolic parameters were observed by either oat or barley products.
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| 5. |
- Cristea, Alexander, et al.
(författare)
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Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells
- 2010
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 9:5, s. 685-697
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Tidskriftsartikel (refereegranskat)abstract
- The skeletal muscle fibre is a syncitium where each myonucleus regulates the gene products in a finite volume of the cytoplasm, i.e., the myonuclear domain (MND). We analysed aging- and gender-related effects on myonuclei organization and the MND size in single muscle fibres from six young (21–31 years) and nine old men (72–96 years), and from six young (24–32 years) and nine old women (65–96 years), using a novel image analysis algorithm applied to confocal images. Muscle fibres were classified according to myosin heavy chain (MyHC) isoform expression. Our image analysis algorithm was effective in determining the spatial organization of myonuclei and the distribution of individual MNDs along the single fibre segments. Significant linear relations were observed between MND size and fibre size, irrespective age, gender and MyHC isoform expression. The spatial organization of individual myonuclei, calculated as the distribution of nearest neighbour distances in 3D, and MND size were affected in old age, but changes were dependent on MyHC isoform expression. In type I muscle fibres, average NN-values were lower and showed an increased variability in old age, reflecting an aggregation of myonuclei in old age. Average MND size did not change in old age, but there was an increased MND size variability. In type IIa fibres, average NN-values and MND sizes were lower in old age, reflecting the smaller size of these muscle fibres in old age. It is suggested that these changes have a significant impact on protein synthesis and degradation during the aging process.
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| 6. |
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| 7. |
- Dyrager, Christine, et al.
(författare)
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Design, Synthesis and Biological Evaluation of Chromone-based p38 MAP Kinase Inhibitors
- 2011
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:20, s. 7427-7431
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Tidskriftsartikel (refereegranskat)abstract
- A series of 3-(4-fluorophenyl)-2-(4-pyridyl)-chromone derivs. were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38 inhibitors with IC50 values in the low nanomolar range (e.g. 8a; IC50 = 17 nm). Addnl., the inhibitors (8a and 8e) demonstrate an excellent selectivity profile towards the p38 kinase among other kinases, as well as inhibition (8e) of p38 signaling in human breast cancer cells. [on SciFinder(R)]
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| 8. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 9. |
- Falck, Peter, et al.
(författare)
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Production of arabinoxylan-oligosaccharide mixtures of varying composition from rye bran by combination of process conditions and type of xylanase.
- 2014
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Ingår i: Bioresource Technology. - : Elsevier BV. - 1873-2976 .- 0960-8524. ; 174, s. 118-125
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study arabinoxylan-oligosaccharide production from rye bran using heat pretreatment and enzymatic hydrolysis. Due to the potential application in foods, the purity of arabinoxylan was also assessed. Rye bran was heat pretreated to improve xylanase-catalyzed hydrolysis of arabinoxylan into arabinoxylan-oligosaccharides. Enzymatic removal of starch and proteins before or after heat pretreatment increased the purity, although at lower yield. The most attractive process resulted in 62% (w/w) arabinoxylan content after ethanol precipitation. Using xylanases from two glycoside hydrolase families (RmXyn10A from GH10 and Pentopan Mono BG from GH11), different mixtures of unsubstituted and arabinose-substituted xylooligosaccharides were produced. GH10 gave a higher yield of short oligosaccharides (60% w/w) with xylobiose as the main product; xylobiose and xylotriose were the main products with GH11 (40% w/w). Thus, heat pretreatment combined with enzymatic hydrolysis can be used to produce arabinoxylan-oligosaccharides from rye bran that are potentially useful in functional foods.
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| 10. |
- Falck, Peter, et al.
(författare)
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Xylooligosaccharides from Hardwood and Cereal Xylans Produced by a Thermostable Xylanase as Carbon Sources for Lactobacillus brevis and Bifidobacterium adolescentis.
- 2013
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 61:30, s. 7333-7340
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Tidskriftsartikel (refereegranskat)abstract
- To compare xylans from forestry with agricultural origins, hardwood xylan (birch) and cereal arabinoxylan (rye) were hydrolyzed using two variants of the xylanase RmXyn10A, full-length enzyme and catalytic module only, from Rhodothermus marinus . Cultivations of four selected bacterial species, using the xylooligosaccharide (XOS) containing hydrolysates as carbon source, showed selective growth of Lactobacillus brevis DSMZ 1264 and Bifidobacterium adolescentis ATCC 15703. Both strains were confirmed to utilize the XOS fraction (DP 2-5), whereas putative arabinoxylooligosaccharides from the rye arabinoxylan hydrolysate were utilized by only B. adolescentis. Escherichia coli did not grow, despite its capability to grow on the monosaccharides arabinose and xylose. It was also shown that Pediococcus parvulus strain 2.6 utilized neither xylose nor XOS for growth. In summary, RmXyn10A or its catalytic module proved suitable for high-temperature hydrolysis of hardwood xylan and cereal arabinoxylan, producing XOS that could qualify as prebiotics for use in functional food products.
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| 11. |
- Freire, Sergio Miranda, et al.
(författare)
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Performance of XML Databases for Epidemiological Queries in Archetype-Based EHRs
- 2012
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Ingår i: Proceedings Scandinavian Conference on Health Informatics 2012. - Linköping : Linköping University Electronic Press. - 9789175197586 ; , s. 51-57
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Konferensbidrag (refereegranskat)abstract
- There are very few published studies regarding the performance of persistence mechanisms for systems that use the openEHR multi level modelling approach. This paper addresses the performance and size of XML databases that store openEHR compliant documents. Database size and response times to epidemiological queries are described. An anonymized relational epidemiology database and associated epidemiological queries were used to generate openEHR XML documents that were stored and queried in four opensource XML databases. The XML databases were considerably slower and required much more space than the relational database. For population-wide epidemiological queries the response times scaled in order of magnitude at the same rate as the number of records (total database size) but were orders of magnitude slower than the original relational database. For individual focused clinical queries where patient ID was specified the response times were acceptable. This study suggests that the tested XML database configurations without further optimizations are not suitable as persistence mechanisms for openEHR-based systems in production if population-wide ad hoc querying is needed.
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| 12. |
- Gräber, Martin, et al.
(författare)
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A novel direct screening method for alkyl glucoside production by glucosidases expressed in E. coli in 96-well plates.
- 2010
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 145, s. 186-192
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Tidskriftsartikel (refereegranskat)abstract
- The present work describes the development of a novel direct screening method, assayed in 96-well format, for evaluation of enzymatic alkyl glycoside production in a hexanol water two-phase system. Alkyl glycosides are surfactants with a range of applications and with good biodegradability and low toxicity. Enzymatic synthesis makes it possible to prepare beta-D-glucopyranosides with high purity. In the developed screening assay, hexyl-ss-D-glucopyranoside was chosen as a model product to be synthesised by reversed hydrolysis in a water-hexanol two-phase system. In a first step the model product is produced by glucosidases expressed in E. coli cells in 96 deep well plates. After phase separation, the hexyl-ss-D-glucopyranoside in the organic phase is degraded enzymatically and the released glucose detected spectrophotometrically at 405nm utilizing peroxidase/glucose oxidase, and the reagent 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS). The aqueous phase is used to monitor hydrolysis of p-NPG at 405nm, allowing use of a ratio of the two assays to compensate for expression differences. The complete method was used for comparison of two different ss-glucosidases, classified under glycoside hydrolase family 1 and 3, respectively, showing a significant difference in their ability to synthesise hexyl-ss-D-glucopyranoside by reversed hydrolysis.
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| 13. |
- Immerzeel, Peter, et al.
(författare)
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Extraction of water-soluble xylan from wheat bran and utilization of enzymatically produced xylooligosaccharides by Lactobacillus, Bifidobacterium and Weissella spp.
- 2014
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Ingår i: LWT - Food Science and Technology. - : Elsevier BV. - 0023-6438. ; 56:2, s. 321-327
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Tidskriftsartikel (refereegranskat)abstract
- Xylan was extracted from wheat bran after heat pretreatment in water using either an autoclave or a microwave oven. Xylooligosaccharides (XOS) were produced from the xylan using the thermostable xylanase RmXyn10A and the potential prebiotic properties of XOS were studied in vitro with different human gut bacteria: Lactobacillus brevis (DSMZ 1269), Bifidobacterium adolescentis (ATCC 15703) and two strains of recently isolated lactic acid bacteria from the species pair Weissella cibaria/confusa. The highest yield of (arabino)xylan with the heat pretreatment was obtained at 185 degrees C for 10 min. Higher temperature led to fewer arabinose substitutions present on the backbone which in turn resulted in a slightly more efficient enzymatic hydrolysis by RmXyn10A. Using the produced XOS hydrolysate as carbon source, xylobiose uptake was confirmed for all bacterial species studied while xylotriose uptake could be confirmed for B. adolescentis and the Weissella strains. The negative control strain Escherichia coli (BL 21) did not use XOS as a carbon source. L brevis, B. adolescentis and the Weissella spp. all showed growth on XOS, verified by increases in cell density, lactic acid and acetic acid production after 48 h incubation. Corresponding increases were not found using the non-hydrolysed xylan as carbon source. (C) 2013 Elsevier Ltd. All rights reserved.
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| 14. |
- Jakobsson, Niklas, 1985, et al.
(författare)
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Are electric vehicles better suited for multi-car households?
- 2014
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Ingår i: European Electric Vehicle Congress Brussels, Belgium, 3rd - 5th December 2014.
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Konferensbidrag (refereegranskat)abstract
- Electric vehicles could reduce CO2 emissions from the transport sector but their limited electric driving range diminishes their utility to users. Two-car households could be better suited for EV adoption since one vehicle could be used for longer trips. However, the number of days requiring adaptation and the differences between the cars in a multi-car household have not been systematically analysed yet. Here, we estimate the probability of daily driving above a fixed threshold for Swedish and German car driving data. We find the vehicles from multi-car-households to require less adaptation and be better suited for EV adoption which we confirm with an economic analysis.
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| 15. |
- Karlsson, Anna K, et al.
(författare)
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Genomic and transcriptional alterations in lung adenocarcinoma in relation to smoking history.
- 2014
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 20:18, s. 4912-4924
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Cigarette smoking is the major pathogenic factor for lung cancer. The precise mechanisms of tobacco-related carcinogenesis, and its effect on the genomic and transcriptional landscape in lung cancer are not fully understood. Experimental Design 1398 (277 never-smokers, 1121 smokers) genomic and 1449 (370 never-smokers, 1079 smokers) transcriptional profiles were assembled from public lung adenocarcinoma cohorts, including matched next-generation DNA-sequencing data (n=423). Unsupervised and supervised methods were used to identify smoking-related copy number alterations (CNAs), predictors of smoking status, and molecular subgroups. Results Genomic meta-analyses showed that never-smokers and smokers harbored a similar frequency of total CNAs, although, specific regions (5q, 8q, 16p, 19p, and 22q) displayed a 20-30% frequency difference between the two groups. Importantly, supervised classification analyses based on CNAs or gene expression could not accurately predict smoking status (balanced accuracies ~60-80%). However, unsupervised multicohort transcriptional profiling stratified adenocarcinomas into distinct molecular subgroups with specific patterns of CNAs, oncogenic mutations, and mutation transversion frequencies that were independent of the smoking status. One subgroup included ~55-90% of never-smokers and ~20-40% of smokers (both current and former) with molecular and clinical features of a less aggressive and smoking-unrelated disease. Given the considerable intra-group heterogeneity in smoking-defined subgroups, especially among former-smokers, our results emphasize the clinical importance of accurate molecular characterization of lung adenocarcinoma. Conclusions The landscape of smoking-related CNAs and transcriptional alterations in adenocarcinomas is complex, heterogeneous, and with moderate differences. Our results support a molecularly distinct less aggressive adenocarcinoma entity, arising in never-smokers and a subset of smokers.
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| 16. |
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| 17. |
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| 18. |
- Kågedal, Matts, et al.
(författare)
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A positron emission tomography study in healthy volunteers to estimate mGluR5 receptor occupancy of AZD2066-Estimating occupancy in the absence of a reference region
- 2013
-
Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 82, s. 160-169
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Tidskriftsartikel (refereegranskat)abstract
- AZD2066 is a new chemical entity pharmacologically characterized as a selective, negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5). Antagonism of mGluR5 has been implicated in relation to various diseases such as anxiety, depression, and pain disorders. To support translation from preclinical results and previous experiences with this target in man, a positron emission tomography study was performed to estimate the relationship between AZD2066 plasma concentrations and receptor occupancy in the human brain, using the mGluR5 radioligand [C-11]-ABP688. The study involved PET scans on 4 occasions in 6 healthy volunteers. The radioligand was given as a tracer dose alone and following oral treatment with different doses of AZD2066. The analysis was based on the total volume of distribution derived fro m each PET-assessment. A non-linear mixed effects model was developed where ten delineated brain regions of interest from all PET scans were included in one simultaneous fit. For comparison the analysis was also performed according to a method described previously by Lassen et al. (1995). The results of the analysis showed that the total volume of distribution decreased with increasing drug concentrations in all regions with an estimated Kipl of 1170 nM. Variability between individuals and occasions in non-displaceable volume of distribution could explain most of the variability in the total volume of distribution. The Lassen approach provided a similar estimate for Kipl, but the variability was exaggerated and difficult to interpret.
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| 19. |
- Kågedal, Matts, et al.
(författare)
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Non-linear mixed effects modelling of positron emission tomography data for simultaneous estimation of radioligand kinetics and occupancy in healthy volunteers
- 2012
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 61:4, s. 849-856
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to develop a model simultaneously estimating (11)C-AZD9272 radioligand kinetics and the relationship between plasma concentration of AZD9272 and receptor occupancy in the human brain.AZD9272 is a new chemical entity pharmacologically characterised as a noncompetitive antagonist at the metabotropic glutamate receptor subtype 5 (mGluR5). Positron emission tomography (PET) was used to measure the time course of ((11)C-AZD9272) in the brain. The study included PET measurements in six healthy volunteers where the radioligand was given as a tracer dose alone as well as post oral treatment with different doses of unlabelled AZD9272. Estimation of radioligand kinetics, including saturation of receptor binding was performed by use of non-linear mixed effects modelling. Data from the regions with the highest (ventral striatum) and lowest (cerebellum) radioligand concentrations were included in the analysis. It was assumed that the extent of non-displaceable brain uptake was the same in both regions while the rate of CNS uptake and the receptor density differed.The results of the analysis showed that AZD9272 binding at the receptor is saturable with an estimated plasma concentration corresponding to 50% occupancy of approximately 200nM. The density of the receptor binding sites was estimated to 800nM and 200nM in ventral striatum and cerebellum respectively. By simultaneously analysing data from several PET measurements and different brain regions in a non-linear mixed effects framework it was possible to estimate parameters of interest that would otherwise be difficult to quantify.
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| 20. |
- Lundemo, Pontus, et al.
(författare)
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Improved transferase/hydrolase ratio through rational design of a family 1 β-glucosidase from Thermotoga neapolitana.
- 2013
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Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 79:11, s. 3400-3405
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Tidskriftsartikel (refereegranskat)abstract
- Alkyl glycosides are attractive surfactants because of their high surface activity and good biodegradability and can be produced from renewable resources. Through enzymatic catalysis one can obtain well-defined alkyl glycosides, something that is very difficult using conventional chemistry. However, there is a need for better enzymes to get a commercially feasible process. A thermostable β-glucosidase from Thermotoga neapolitana, TnBgl1A, from the well-studied glycoside hydrolase family 1 was mutated in an attempt to improve its value for synthesis of alkyl glycosides. This was done by rational design using prior knowledge from structural homologues together with a recently generated model of the enzyme in question. Three out of four studied mutations increased the hydrolytic reaction rate in aqueous environment while none displayed this property in presence of an alcohol acceptor. This shows that even if the enzyme resides in a separate aqueous phase, the presence of an organic solvent has great influence. We could also show that a single amino acid replacement in a less studied part of the aglycone subsite, N220F, improves the specificity for transglycosylation 7-fold and thereby increases the potential yield of alkyl glycoside from 17 % to 58 %.
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| 21. |
- Lundemo, Pontus, et al.
(författare)
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Preparation of two glycoside hydrolases for use in micro-aqueous media
- 2014
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Ingår i: Journal of Molecular Catalysis B: Enzymatic. - : Elsevier BV. - 1873-3158 .- 1381-1177. ; 108, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Enzymatic synthesis of alkyl glycosides using glycoside hydrolases is well studied, but has yet to reach industrial scale, primarily due to limited yields. Reduced water content should increase yields by limiting the unwanted hydrolytic side reaction. However, previous studies have shown that a reduction in water content surprisingly favors hydrolysis over transglycosylation. In addition, glycoside hydrolases normally require a high degree of hydration to function efficiently. This study compares six enzyme preparation methods to improve resilience and activity of two glycoside hydrolases from Thermotoga neapolitana (TnBgl3B and TnBgl1A) in micro-aqueous hexanol. Indeed, when adsorbed onto Accurel MP-1000 both enzymes increasingly favored transglycosylation over hydrolysis at low hydration, in contrast to freeze-dried or untreated enzyme. Additionally, they displayed 17–70× higher reaction rates compared to freeze-dried enzyme at low water activity, while displaying comparable or lower activity for fully hydrated systems. These results provide valuable information for use of enzymes under micro-aqueous conditions and build toward utilizing the full synthetic potential of glycoside hydrolases.
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| 22. |
- Olsson, Per-Magnus, 1976-
(författare)
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Positioning Algorithms for Surveillance Using Unmanned Aerial Vehicles
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surveillance is an important application for unmanned aerial vehicles (UAVs). The sensed information often has high priority and it must be made available to human operators as quickly as possible. Due to obstacles and limited communication range, it is not always possible to transmit the information directly to the base station. In this case, other UAVs can form a relay chain between the surveillance UAV and the base station. Determining suitable positions for such UAVs is a complex optimization problem in and of itself, and is made even more difficult by communication and surveillance constraints.To solve different variations of finding positions for UAVs for surveillance of one target, two new algorithms have been developed. One of the algorithms is developed especially for finding a set of relay chains offering different trade-offs between the number of UAVsand the quality of the chain. The other algorithm is tailored towards finding the highest quality chain possible, given a limited number of available UAVs.Finding the optimal positions for surveillance of several targets is more difficult. A study has been performed, in order to determine how the problems of interest can besolved. It turns out that very few of the existing algorithms can be used due to the characteristics of our specific problem. For this reason, an algorithm for quickly calculating positions for surveillance of multiple targets has been developed. This enables calculation of an initial chain that is immediately made available to the user, and the chain is then incrementally optimized according to the user’s desire.
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| 23. |
- Orwoll, Eric S., et al.
(författare)
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Evidence for Geographical and Racial Variation in Serum Sex Steroid Levels in Older Men
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:10, s. E151-E160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men. Methods: Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay. Results: There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites. Conclusions: On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.
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| 24. |
- Patel, Ami, et al.
(författare)
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Evidence for xylooligosaccharides utilization in Weissella strains isolated from Indian fermented foods and vegetables.
- 2013
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Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968 .- 0378-1097. ; 346:1, s. 20-28
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Six strains isolated from fermented food were by 16S rDNA sequencing identified as Weissella species, clustering with the species-pair W. confusa/ W. cibaria. The strains were analysed for growth on glucose, xylose and xylooligosaccharides (XOS). All strains were xylose positive using the API CHL 50 test. Growth on XOS was observed for strain 85, 92, 145 and AV1, firstly by optical density measurements in microtiter plates and secondly in batch cultures also confirming concomitant decrease in pH. Analysis of XOS before and after growth established consumption in the DP2 - DP5 range in the four XOS-fermenting strains. XOS were consumed simultaneously with glucose, while xylose was consumed after glucose depletion. Cell-associated β-xylosidase activity was detected in the XOS fermenting strains. Analysis of genomic data suggests this activity to be linked to genes encoding glycoside hydrolases from family 3, 8 or 43. No endo-β-xylanase activity was detectable. Main fermentation end products were lactate and acetate. A higher ratio of acetic acid/lactic acid was produced during growth on XOS compared to growth on glucose. This is the first report on utilization of XOS in Weissella, indicating an increased probiotic potential for XOS-utilizing strains from the species pair W. confusa/ W. cibaria, but also showing that XOS utilization is strain-dependent for these species. This article is protected by copyright. All rights reserved.
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| 25. |
- Plötz, Patrick, et al.
(författare)
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On the distribution of individual daily vehicle driving distances
- 2014
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Ingår i: European Electric Vehicle Congress Brussels, Belgium, 3rd - 5th December 2014.
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Konferensbidrag (refereegranskat)abstract
- The vehicle kilometres travelled (VKT) by individual passenger cars vary strongly between days. This is important for electric vehicles since trips larger than the electric range reduce their utility. Here we analyse different distribution functions for the variation in daily VKT with three sets of travel data. In contrast to the literature, no analysed distribution stands out best. We apply our findings for the distribution functions to estimate the number of days per year with driving distance larger than 100 km and find that the distributions differ in their predictions of the number of such days.
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| 26. |
- Renner, Johan, 1977-
(författare)
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Towards Subject Specific Aortic Wall Shear Stress : a combined CFD and MRI approach
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The cardiovascular system is an important part of the human body since it transports both energy and oxygen to all cells throughout the body. Diseases in this system are often dangerous and cardiovascular diseases are the number one killer in the western world. Common cardiovascular diseases are heart attack and stroke, which origins from obstructed blood flow. It is generally important to understand the causes for these cardiovascular diseases. The main causes for these diseases are atherosclerosis development in the arteries (hardening and abnormal growth). This transform of the arterial wall is believed to be influenced by the mechanical load from the flowing blood on the artery and especially the tangential force the wall shear stress. To retrieve wall shear stress information in arteries invivo is highly interesting due to the coupling to atherosclerosis and indeed a challenge. The goal of this thesis is to develop, describe and evaluate an in-vivo method for subject specific wall shear stress estimations in the human aorta, the largest artery in the human body. The method uses an image based computational fluid dynamics approach in order to estimate the wall shear stress. To retrieve in-vivo geometrical descriptions of the aorta magnetic resonance imaging capabilities is used which creates image material describing the subject specific geometry of the aorta. Magnetic resonance imaging is also used to retrieve subject specific blood velocity information in the aorta. Both aortic geometry and velocity is gained at the same time. Thereafter the image material is interpreted using level-set segmentation in order to get a three-dimensional description of the aorta. Computational fluid dynamics simulations is applied on the subject specific aorta in order to calculate time resolved wall shear stress distribution at the entire aortic wall included in the actual model.This work shows that it is possible to estimate subject specific wall shear stress in the human aorta. The results from a group of healthy volunteers revealed that the arterial geometry is very subject specific and the different wall shear stress distributions have general similarities but the level and local distribution are clearly different. Sensitivity (on wall shear stress) to image modality, the different segmentation methods and different inlet velocity profiles have been tested, which resulted in these general conclusions:The aortic diameter from magnetic resonance imaging became similar to the reference diameter measurement method.The fast semi-automatic level-set segmentation method gave similar geometry and wall shear stress results when compared to a reference segmentation method.Wall shear stress distribution became different when comparing a simplified uniform velocity profile inlet boundary condition with a measured velocity profile.The method proposed in this thesis has the possibility to produce subject specific wall shear stress distribution in the human aorta. The method can be used for further medical research regarding atherosclerosis development and has the possibility for usage in clinical work.
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| 27. |
- Staaf, Johan, et al.
(författare)
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Landscape of somatic allelic imbalances and copy number alterations in human lung carcinoma
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:9, s. 2020-2031
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the worldwide leading cause of death from cancer and has been shown to be a heterogeneous disease at the genomic level. To delineate the genomic landscape of copy number alterations, amplifications, loss-of-heterozygosity (LOH), tumor ploidy and copy-neutral allelic imbalance in lung cancer, microarray-based genomic profiles from 2,141 tumors and cell lines including adenocarcinomas (AC, n = 1,206), squamous cell carcinomas (SqCC, n = 467), large cell carcinomas (n = 37) and small cell lung carcinomas (SCLC, n = 88) were assembled from different repositories. Copy number alteration differences between lung cancer histologies were confirmed in 285 unrelated tumors analyzed by BAC array comparative genomic hybridization. Tumor ploidy patterns were validated by DNA flow cytometry analysis of 129 unrelated cases. Eighty-nine recurrent copy number alterations (55 gains, 34 losses) were identified harboring genes with gene expression putatively driven by gene dosage through integration with gene expression data for 496 cases. Thirteen and 26 of identified regions discriminated AC/SqCC and AC/SqCC/SCLC, respectively, while 48 regions harbored recurrent (n > 15) high-level amplifications comprising established and putative oncogenes, differing in frequency and coamplification patterns between histologies. Lung cancer histologies displayed differences in patterns/frequency of copy number alterations, genomic architecture, LOH, copy-neutral allelic imbalance and tumor ploidy, with AC generally displaying less copy number alterations and allelic imbalance. Moreover, a strong association was demonstrated between different types of copy number alterations and allelic imbalances with tumor aneuploidy. In summary, these analyses provide a comprehensive overview of the landscape of genomic alterations in lung cancer, highlighting differences but also similarities between subgroups of the disease.
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| 28. |
- Vigren, Patrick, et al.
(författare)
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Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundKleine Levin Syndrome (KLS) is a rare disorder of periodic hypersomnia and behavioural disturbances in young individuals. It has previously been shown to be associated with disturbances of working memory (WM), which, in turn, was associated with higher activation of the thalamus with increasing WM load, demonstrated with functional magnetic resonance imaging (fMRI). In this study we aimed to further elucidate how these findings are related to the metabolism of the thalamus.MethodsfMRI and magnetic resonance spectroscopy were applied while performing a WM task. Standard metabolites were examined: n-acetylaspartate (NAA), myo-inositol, choline, creatine and glutamate-glutamine. Fourteen KLS-patients and 15 healthy controls participated in the study. The patients with active disease were examined in asymptomatic periods.ResultsThere was a statistically significant negative correlation between thalamic fMRI-activation and thalamic NAA, i.e., high fMRI-activation corresponded to low NAA-levels. This correlation was not seen in healthy controls. Thalamic levels of NAA in patients and controls showed no significant differences between the groups. None of the other metabolites showed any co-variation with fMRI-activiation.ConclusionThis study shows negative correlation between NAA-levels and fMRI-activity in the left thalamus of KLS-patients while performing a WM task. This correlation could not be found in healthy control subjects, primarily interpreted as an effect of increased effort in the patient group upon performing the task. It might indicate a disturbance in the neuronal networks responsible for WM in KLS patients, resulting in higher effort at lower WM load, compared with healthy subjects. The general relationship between NAA and BOLD-signal is also discussed in the article.
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| 29. |
- Zheng, Hou-Feng, et al.
(författare)
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WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- 2012
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Ingår i: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
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