| 21. |
- Knutsen Rydberg, Ellen, 1969, et al.
(författare)
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Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
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Ingår i: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
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| 22. |
- Lindquist, Kajsa Ericson, et al.
(författare)
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Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:21, s. 34796-34810
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Tidskriftsartikel (refereegranskat)abstract
- Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the 533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135 successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH fusion positive case was missed by the NanoString assay. Stratification of the 533-sample cohort based on actionable alterations in 11 oncogenes revealed that 66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not otherwise specified harbored ≥1 alteration. In adenocarcinoma, 10.6% of patients (50.3% if including KRAS) could potentially be eligible for emerging therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1% with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are feasible in NSCLC for clinical diagnostics, identifying notable proportions of patients potentially eligible for emerging molecular therapeutics.
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| 23. |
- Mehanovic, Sanela
(författare)
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The Potential and Challenges of the Use of Dynamic Software in Upper Secondary Mathematics : Students’ and Teachers’ Work with Integrals in GeoGebra Based Environments
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An introduction of computer software into mathematics classrooms makes the didactical situation more complex compared with previous learning environments (Blomhøj, 2005). A technological tool becoming a mathematic work tool in the hands of the students is a process that has turned up unexpectedly complex (Artigue, 2002). In addition to this problem, the teachers as the users of the tool go through the same process, while, at the same time, trying to integrate the tool into their teaching activities in a meaningful way. For these reasons it seems important to contribute to the research focused on the learning and teaching conditions in environments, where computer software is newly introduced, in order to better understand impacts of the introduction of different software in mathematics classrooms.In this study the dynamic mathematical software GeoGebra was used. GeoGebra is freely available for a number of platforms and has drawn much attention during the last years with growing user communities (www.GeoGebra.org). However, being generally available just recently, there are, comparatively, few studies on the use of GeoGebra in classroom settings.In this thesis the introduction and integration of GeoGebra was investigated in two studies with different perspectives. In the first study students’ work with GeoGebra in their mathematical activities related to the integral concept has been researched. In the second study teachers’ utilization of the didactical potential has been investigated. The results of the two studies show that GeoGebra as a mathematical tool in the hands of the students and the teachers can have a significant role in supporting their mathematical work if exploited in a, from a didactical perspective, adequate way. A learning and teaching environment based on GeoGebra bring with it a possibility to work with mathematical concepts in a broader way compared with blackboard based classrooms. GeoGebra’s facilities makes it possible to communicate mathematics in different ways and expressing mathematical concepts in different representations in a more direct way than in non dynamical environments. Communicating mathematics in different ways and expressing mathematics knowledge through different representations is of significant importance for students, not least in relation to the new curriculum for mathematics in Sweden (The Swedish National Agency for Education, 2011), where these aspects are explicitly named as aims for students to work towards.On the other hand, the investigations also showed that the introduction and the integration of GeoGebrawas a complex process for both the students and the teachers in this research. The introduction and integration of the software in the students’ mathematical activities made the didactical situation more complex and a differentiation of students’ work with the software was observed. For some students the use of the software seemingly supported their mathematical work, and at the same time for some students the result was the opposite; the use of the software was seen as a disturbing factor in their mathematical activities. When it comes to the study of teachers’ work with GeoGebra the investigations revealed that they encountered different types of obstacles that prevented them from utilizing the full didactical potential of the software in their teaching of mathematics. Three different types of obstacles were identified:technical - a teacher is not able to operate the software in the intended way;epistemological - a teacher is not aware of the didactical potential of GeoGebra and howto exploit it in in a way that supports students’ learning of integrals;didactical - a teacher is not aware of the complexity of technology based environments or he/she is aware of this aspect, but not comfortable with his/her competence in carrying out the process of integration of the software into his/her teaching without external help and support.Even if it is difficult to see the software detached from the context in this research, it seems that many of the obstacles perceived by the teachers in the experimental group, as well as difficulties students perceived in their work with the software, were related to the fact that they were inexperienced with the software and, consequently, lacked in knowledge in how to exploit its features in their mathematical activities. As it seems, the teachers would encounter the same obstacles every time they try to integrate a new, to them unfamiliar, software into their teaching practice. Also many of the students would experience same difficulties if they are not adequately supported in this process. Based on this, there are reasons to believe that problems with integration of GeoGebra into mathematics classrooms identified in this research would be similar in relation to integration of other dynamic mathematic software into mathematics classrooms, or even broader, other types of software as e.g. Computer Algebra Systems (CAS), as long as the integration considers the use of an unfamiliar software.
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| 24. |
- Salomonsson, Annette, et al.
(författare)
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Histological specificity of alterations and expression of KIT and KITLG in non-small cell lung carcinoma.
- 2013
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 52:11, s. 1088-1096
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of molecules within important oncogenetic pathways may have future implications for development of therapies and biomarkers in lung cancer. One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated alterations and expression of KIT and its ligand, KITLG (also known as SCF), in 72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA expression levels, and protein expression were assayed using array-based comparative genomic hybridization, real-time quantitative reverse transcription PCR and immunohistochemistry, respectively. For validation, we investigated copy number alterations and mRNA expression in external microarray data sets of 1,600 and 555 primary lung tumors, respectively. Positivity for KIT staining was most common in large cell neuroendocrine carcinoma (LCNEC) which also showed the highest KIT mRNA expression levels whereas expression was lowest in squamous cell carcinoma (SqCC). KIT mRNA expression levels were higher in KIT immunopositive samples, but expression was not affected by KIT copy numbers. Copy number gains of KIT were significantly more frequent in SqCC compared with adenocarcinoma in our own series and in the 1,600-sample data set. Immunopositivity for both KIT and KITLG in the same tumor was rare except in LCNEC. Our results highlight an increased KIT mRNA expression and frequent KIT immunopositivity in LCNEC but point out a poor correlation between KIT copy numbers and expression in SqCC, perhaps reflecting the existence of a protective mechanism against KIT alterations in this subgroup. © 2013 Wiley Periodicals, Inc.
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| 25. |
- 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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| 26. |
- Stobaeus, Per, et al.
(författare)
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En bukett av bibliska blomster
- 2008
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Ingår i: Förbistringar och förklaringar: festskrift till Anders Piltz. - 9789187976292 ; , s. 575-585
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 27. |
- Örtorp, Anders, 1964, et al.
(författare)
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The fit of cobalt-chromium three-unit fixed dental prostheses fabricated with four different techniques: A comparative in vitro study.
- 2011
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Ingår i: Dental materials. - : Elsevier BV. - 1879-0097 .- 0109-5641. ; 27:4, s. 356-363
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study sought to evaluate and compare the marginal and internal fit in vitro of three-unit FDPs in Co-Cr made using four fabrication techniques, and to conclude in which area the largest misfit is present. METHODS: An epoxy resin master model was produced. The impression was first made with silicone, and master and working models were then produced. A total of 32 three-unit Co-Cr FDPs were fabricated with four different production techniques: conventional lost-wax method (LW), milled wax with lost-wax method (MW), milled Co-Cr (MC), and direct laser metal sintering (DLMS). Each of the four groups consisted of eight FDPs (test groups). The FDPs were cemented on their cast and standardised-sectioned. The cement film thickness of the marginal and internal gaps was measured in a stereomicroscope, digital photos were taken at 12× magnification and then analyzed using measurement software. Statistical analyses were performed with one-way ANOVA and Tukey's test. RESULTS: Best fit based on the means (SDs) in μm for all measurement points was in the DLMS group 84 (60) followed by MW 117 (89), LW 133 (89) and MC 166 (135). Significant differences were present between MC and DLMS (p<0.05). The regression analyses presented differences within the parameters: production technique, tooth size, position and measurement point (p<0.05). SIGNIFICANCE: Best fit was found in the DLMS group followed by MW, LW and MC. In all four groups, best fit in both abutments was along the axial walls and in the deepest part of the chamfer preparation. The greatest misfit was present occlusally in all specimens.
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| 28. |
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| 29. |
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| 30. |
- Adelmann, Kenneth, et al.
(författare)
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Språkutveckling, medier och demokrati
- 2014
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Ingår i: Medie- och informationskunnighet i Norden. - Göteborg : Nordicom. - 9789186523886 ; , s. 117-129
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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