| 1. |
- Schultheiss, Fredrik, et al.
(författare)
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Cost Optimization by Incremental Production Improvements of Metal Cutting Operations
- 2011
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Ingår i: [Host publication title missing]. ; , s. 540-547
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Konferensbidrag (refereegranskat)abstract
- The focus of this project has been to find a method on how to do production improvements systematically in the case of manufacturing by means of metal cutting operations. Typically every company determines their cutting data with the help of previous experiences as well as recommendations made by the tool manufacturers. These chosen cutting data may be the optimal settings for the specific operation although the probability for this is very slim. Some large companies have resources to investigate and find the optimum cutting data by themselves but this is usually not the case for SMEs. These companies need a clear and logical method on how to find the machining optimum while not causing too many delays or scraped parts during the normal production. The goal of this research was to find a method to incrementally optimize the production in terms of manufacturing costs of the machined parts in SMEs. The proposed method is illustrated by an analysis of the results obtained from a case study at a small Swedish company. The present work constitutes a good foundation for the optimization of the production process and thereby has a strong relevance toward the area of sustainable production.
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| 2. |
- Schultheiss, Fredrik, et al.
(författare)
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Machinability of duplex stainless steels - A study with focus on the tool wear behaviour
- 2011
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Ingår i: [Host publication title missing]. ; , s. 271-277
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Konferensbidrag (refereegranskat)abstract
- This article presents research done in order to analyse the machinability of duplex stainless steel with coated carbide tools during turning operations. Although duplex stainless steel has existed for about 70 years fairly little work has been published in the area of investigating the different aspects of the machining of these materials. In this research project three different kinds of duplex stainless steels and their properties have been examined. These materials where SAF 2507, SAF 2205 and LDX 2101 which together covers a large part of the duplex stainless steels that are commercially available today. This study focuses on analysing the tool wear behaviour in an attempt to better understand the actual wear patterns during machining, not only the more traditional ones that are in common use today. Some additional tests were also done in order to get a better understanding of the machinability of duplex stainless steel in general. Theories and concepts that are related to the analysing of machinability will be presented, most of which have been previously validated and in use for a long time. Adhesive wear of the cutting tool, in many cases severe, was to some extent found at all different cutting data investigated.
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| 3. |
- Ståhl, Patrik, Dr., et al.
(författare)
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Visualization and analysis of gene expression in tissue sections by spatial transcriptomics
- 2016
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 353:6294, s. 78-82
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of the pattern of proteins or messenger RNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call "spatial transcriptomics," that allows visualization and quantitative analysis of the transcriptome with spatial resolution in individual tissue sections. By positioning histological sections on arrayed reverse transcription primers with unique positional barcodes, we demonstrate high-quality RNA-sequencing data with maintained two-dimensional positional information from the mouse brain and human breast cancer. Spatial transcriptomics provides quantitative gene expression data and visualization of the distribution of mRNAs within tissue sections and enables novel types of bioinformatics analyses, valuable in research and diagnostics.
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| 4. |
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| 5. |
- Andersson, Lars, 1977, et al.
(författare)
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A web tool for finding gene candidates associated with experimentally induced arthritis in the rat
- 2005
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Ingår i: Arthritis Res Ther. - : BioMed Central Ltd.. ; 7:3, s. R485-R492
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Tidskriftsartikel (refereegranskat)abstract
- Rat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at http://ratmap.org/cgc. The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information.
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| 6. |
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| 7. |
- Andersson, Lars, 1977, et al.
(författare)
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Distribution of candidate genes for experimentally induced arthritis in rats
- 2010
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Ingår i: BMC GENOMICS. - : BioMed Central Ltd.. - 1471-2164. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background Rat models are frequently used to link genomic regions to experimentally induced arthritis in quantitative trait locus (QTL) analyses. To facilitate the search for candidate genes within such regions, we have previously developed an application (CGC) that uses weighted keywords to rank genes based on their descriptive text. In this study, CGC is used for analyzing the localization of candidate genes from two viewpoints: distribution over the rat genome and functional connections between arthritis QTLs. Methods To investigate if candidate genes identified by CGC are more likely to be found inside QTLs, we ranked 2403 genes genome wide in rat. The number of genes within different ranges of CGC scores localized inside and outside QTLs was then calculated. Furthermore, we investigated if candidate genes within certain QTLs share similar functions, and if these functions could be connected to genes within other QTLs. Based on references between genes in OMIM, we created connections between genes in QTLs identified in two distinct rat crosses. In this way, QTL pairs with one QTL from each cross that share an unexpectedly high number of gene connections were identified. The genes that were found to connect a pair of QTLs were then functionally analysed using a publicly available classification tool. Results Out of the 2403 genes ranked by the CGC application, 1160 were localized within QTL regions. No difference was observed between highly and lowly rated genes. Hence, highly rated candidate genes for arthritis seem to be distributed randomly inside and outside QTLs. Furthermore, we found five pairs of QTLs that shared a significantly high number of interconnected genes. When functionally analyzed, most genes connecting two QTLs could be included in a single functional cluster. Thus, the functional connections between these genes could very well be involved in the development of an arthritis phenotype. Conclusions From the genome wide CGC search, we conclude that candidate genes for arthritis in rat are randomly distributed between QTL and non-QTL regions. We do however find certain pairs of QTLs that share a large number of functionally connected candidate genes, suggesting that these QTLs contain a number of genes involved in similar functions contributing to the arthritis phenotype.
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| 8. |
- Andersson, Lars, 1977, et al.
(författare)
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Finding Genes Contributing to the Arthritis Phenotype by Comparing Rat and Human Genome Data
- 2004
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Ingår i: Health Informatics Journal. - : SAGE Publications. - 1460-4582 .- 1741-2811. ; 10:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Published quantitative trait locus (QTL) data, as well as all known rat genes and DNA markers, have since 1993 been collected and made easily accessible at the rat genome database, RatMap. The objective of the present study is to fully integrate available data concerning rat models with human genome information. The final goal of this process is to make results from any rat model experiment directly applicable to humans. The overall goal of this work is to create an automatic system which, for any given rat chromosomal region associated with a QTL, will characterize both mapped rat genes and all putative homologous human genes in that region. This article reports the use of the web application to find human gene candidates contributing to an arthritis phenotype.
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| 9. |
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| 10. |
- Asp, Michaela, et al.
(författare)
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A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart
- 2019
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 179:7, s. 1647-
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Tidskriftsartikel (refereegranskat)abstract
- The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.
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| 11. |
- Asp, Michaela, et al.
(författare)
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An organ‐wide gene expression atlas of the developing human heart
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The human developing heart holds a greater proportion of stem-cell-like cells than the adult heart. However, it is not completely understood how these stem cells differentiate into various cardiac cell types. We have performed an organ-wide transcriptional landscape analysis of the developing heart to advance our understanding of cardiac morphogenesis in humans. Comprehensive spatial gene expression analyses identified distinct profiles that correspond not only to individual chamber compartments, but also distinctive regions within the outflow tract. Furthermore, the generated spatial expression reference maps facilitated the assignment of 3,787 human embryonic cardiac cells obtained from single-cell RNA-sequencing to an in situlocation. Through this approach we reveal that the outflow tract contains a wider range of cell types than the chambers, and that the epicardium expression profile can be traced to several cell types that are activated at different stages of development. We also provide a 3D spatial model of human embryonic cardiac cells to enable further studies of the developing human heart.
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| 12. |
- Asp, Michaela, et al.
(författare)
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Spatial Isoform Profiling within Individual Tissue Sections
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Spatial Transcriptomics has been shown to be a persuasive RNA sequencingtechnology for analyzing cellular heterogeneity within tissue sections. Thetechnology efficiently captures and barcodes 3’ tags of all polyadenylatedtranscripts from a tissue section, and thus provides a powerful platform whenperforming quantitative spatial gene expression studies. However, the currentprotocol does not recover the full-length information of transcripts, andconsequently lack information regarding alternative splice variants. Here, weintroduce a novel protocol for spatial isoform profiling, using SpatialTranscriptomics barcoded arrays.
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| 13. |
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| 14. |
- Bass, Tarek, et al.
(författare)
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In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with In-111 via a DOTA chelator. The residence time of In-111-DOTA-3A3 in blood was extended when compared with the monomeric affibody molecule. In-111-DOTA-3A3 accumulated specifically in HER3-expressing BxPC-3 xenografts in mice. However, In-111-DOTA-3A3 cleared more rapidly from blood than a size-matched control construct In-111-DOTA-TAT, most likely due to sequestering of 3A3 by mErbB3, the murine counterpart of HER3. Repeated dosing and increase of injected protein dose decreased uptake of In-111-DOTA-3A3 in mErbB3-expressing tissues. Encouragingly, growth of BxPC-3 xenografts in mice was delayed in an experimental (pilot-scale) therapy study using 3A3. We conclude that the 3A3 affibody format seems promising for treatment of HER3-overexpressing tumours.
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| 15. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human.
- 2002
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Ingår i: Mammalian genome : official journal of the International Mammalian Genome Society. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 13:6, s. 302-9
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Tidskriftsartikel (refereegranskat)abstract
- The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related ( Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.
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| 16. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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Evolutionary aspects of the genomic organization of rat chromosome 10.
- 2002
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Ingår i: Cytogenetic and genome research. - : S. Karger. - 1424-8581 .- 1424-859X. ; 96:1-4, s. 52-9
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Tidskriftsartikel (refereegranskat)abstract
- Using FISH and RH mapping a chromosomal map of rat chromosome 10 (RNO10) was constructed. Our mapping data were complemented by other published data and the final map was compared to maps of mouse and human chromosomes. RNO10 contained segments homologous to mouse chromosomes (MMU) 11, 16 and 17, with evolutionary breakpoints between the three segments situated in the proximal part of RNO10. Near one of these breakpoints (between MMU17 and 11) we found evidence for an inversion ancestral to the mouse that was not ancestral to the condition in the rat. Within each of the chromosome segments identified, the gene order appeared to be largely conserved. This conservation was particularly clear in the long MMU11-homologous segment. RNO10 also contained segments homologous to three human chromosomes (HSA5, 16, 17). However, within each segment of conserved synteny were signs of more extensive rearrangements. At least 13 different evolutionary breakpoints were indicated in the rat-human comparison. In contrast to what was found between rat and mouse, the rat-human evolutionary breaks were distributed along the entire length of RNO10.
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| 17. |
- Behboudi, A, et al.
(författare)
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Functional significance of absence : The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel
- 2002
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Ingår i: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-848
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2–6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 18. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.
- 2002
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-8
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2-6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 19. |
- Berglund, Emelie, et al.
(författare)
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Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
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| 20. |
- Block, K, et al.
(författare)
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Characterization of a minichromosome derived from the transposing element TE1 in Drosophila melanogaster
- 1991
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Ingår i: Hereditas. - : Wiley-Blackwell Publishing, Inc.. - 0018-0661. ; , s. 82-83
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Konferensbidrag (refereegranskat)abstract
- The transposing element TEI contains the structural genes white and roughest from the Drosophilr X-chromosome. These genes are flanked by FB-elements, which are responsible for the mobility. At one occasion the TE, probably together with an adjacent segment in chromosome 2. has formed a minichromosome. This chromosome contains both the structural genes, the FB-elements,some centromeric and/or telomeric heterochromatin. It probably has a centromere as well, as it is transferred to the offspring at a high rate. From this minichromosome a smaller one has originated, probably through the loss of the region from chromosome 2 and some heterochromatin. This smaller minichromosome has been characterized in the following way: 1. Size determination hy pulsed field gel electrophoresis. -The chromosome turned out to be little more than one megabase. 2. y-irradiation of DNA from the minichromosome. ~ The aim of this experiment is to find out if the chromosome is circular or linear. A radiation dose which causes one break within a circle ought to accumulate DNA of the same size as the minichromosome. In this case no accumulation occurred and thus the chromosome is probably linear. 3. Cloning of sequences from the minichromosome. ~ A low melting agarose gel was run and a fragment was cut out from a region which contained DNA fragments of the same size as the minichromosome. The DNA was cut simultaneously by EcoR I and Pst I and ligated into the vector pBS containing T7 and T3 primers. The ligated DNA was amplified by the PCR method, which rendered several fragments of varying size. These fragments were ligated into the vector pCR1000TM. Positive clones are being analysed at present. With these clones we intend to construct a map of the minichromosome.
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| 21. |
- Block, K, et al.
(författare)
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Minichromosomes in Drosophila melanogaster derived from the transposing element TE1
- 1990
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Ingår i: Chromosoma. - : Springer. - 0009-5915 .- 1432-0886. ; 99:5, s. 336-343
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Tidskriftsartikel (refereegranskat)abstract
- A minichromosome has originated from the transposing element TE1. This autonomously replicating chromosome contains the structural genes white and roughest, from the Drosophila X chromosome. It arose within a stock carrying TE1 at 45F on chromosome 2. In addition to the w and rst genes, the minichromosome may carry section 45C-45F from chromosome 2. It is inherited by 33%-47% of the offspring. By this criterion it carries a centromere, although the origin of the centromere is unknown. From this minichromosome a still smaller one has originated, probably through the loss of all material from chromosome 2 together with some heterochromatin. At the same time a duplication of white and roughest could have taken place. This chromosome has a strange morphology and is more frequently lost in meiosis than the larger one, but is still transmitted to about 29%-37% of the progeny of one parent heterozygous for the minichromosome. In both cases the flies have variegated eyes, probably as a result of position-effect variegation. The variegation pattern is influenced by factors in the X chromosome. The size of the smaller minichromosome is little more than 1 Mb as determined by pulsed field gel electrophoresis.
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| 22. |
- Bobjer, Johannes, et al.
(författare)
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Location of retroperitoneal lymph node metastases in upper tract urothelial carcinoma : results from a prospective lymph node mapping study
- 2023
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 57, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC).Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND).Design, setting, and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node–positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates.Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used.Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates.Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited.Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.
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| 23. |
- Boutajangout, Allal, et al.
(författare)
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Affibody-Mediated Sequestration of Amyloid beta Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model
- 2019
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid beta (anti-A beta) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of A beta-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted Z(SYM73)-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric Z(SYM73) affibody for sequestering of monomeric A beta-peptides and an ABD for extension of its in vivo half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with Z(SYM73)-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported in vivo investigation of a systemically delivered scaffold protein against monomeric A beta, demonstrating a therapeutic potential for prevention of AD.
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| 24. |
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| 25. |
- Broström, Tor, et al.
(författare)
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A method to assess the potential for and consequences of energy retrofits in Swedish historic buildings
- 2014
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Ingår i: The Historic Environment. - : Maney Publishing. - 1756-7505 .- 1756-7513. ; 5:2, s. 150-166
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Tidskriftsartikel (refereegranskat)abstract
- Tor Broström is a Professor in Conservation at Uppsala University, Campus Gotland, Sweden. With a background in engineering, his research focuses on indoor climate and energy conservation in historic buildings. He is coordinator of the Swedish national research programme on energy efficiency in historic buildings. Petra Eriksson, is a lecturer and PhD candidate in conservation at Uppsala University, Campus Gotland, Sweden. Petra has a background in the applied field of conservation and her research is in the field of heritage conservation in relation to energy efficiency. Linn Liu is a PhD candidate in the Division of Energy Systems, Department of Management and Engineering at Linköping University, Sweden. Her research area is within energy efficiency and cost efficiency of multifamily buildings and historic buildings. Patrik Rohdin is Associate Professor in the Division of Energy Systems, Department of Management and Engineering at Linköping University, Sweden. Patrik is conducting research related to energy efficiency in the built environment and building simulation and is active within the national interdisciplinary research programme, program energy systems. Bahram Moshfegh is a Professor and Head of the Division of Energy Systems, Department of Management and Engineering at Linköping University, Sweden. Professor Moshfegh has been active in the following research areas: mathematical modelling and measuring techniques for air and energy flow in buildings, energy-efficient HVAC systems and local and regional energy systems. Fredrik Ståhl is Senior Researcher in the Department of Energy Technology at SP Swedish Technical Research Institute. Currently, his research is focused on energy efficiency in historic buildings. The Swedish research project 'Potential and Policies for Energy Efficiency in Swedish Historic Buildings' aims to investigate the interdependency between political energy targets and effects on the built heritage. The fi rst part of this paper presents an iterative and interactive method to assess the potential for and consequences of improving the energy performance in a stock of historic buildings. Key elements in the method are: categorisation of the building stock, identifying targets, assessment of measures, and life-cycle cost optimisation. In the second part of the paper, the method is applied to a typical Swedish building. The selected case study shows how the method allows for an interaction between the quantitative assessment of the technoeconomic optimisation and the qualitative assessment of vulnerability and other risks. Through a multidisciplinary dialogue and iteration it is possible to arrive at a solution that best balances energy conservation and building conservation in a given decision context.
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| 26. |
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| 27. |
- Bushlya, Volodymyr, et al.
(författare)
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On the Analytical Representation of Chip Area and Tool Geometry when Oblique Turning with Round Tools. Part 1: Chip Area Parameters under Variation of Side and Back Rake Angle
- 2015
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Ingår i: 15th CIRP Conference on Modelling of Machining Operations (15TH CMMO). - : Elsevier BV. - 2212-8271. ; 31, s. 417-422
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Konferensbidrag (refereegranskat)abstract
- Chip area parameters, such as undeformed chip thickness, equivalent chip thickness, contact edge length, etc., along with tool angles are among defining for the mechanical and thermal conditions of the cutting process. This paper considers the case of external turning with a round insert under variation, in wide range, of back and side rake angles and their influence on the main chip area and surface roughness parameters. Influence of other process variables, such as feed, depth-of-cut and nose radius, is also studied. The developed analytical models and algorithms allow, not only to study the fundamental relationships, but to apply them in the design of new tools for conventional and rotary turning.
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| 28. |
- Bushlya, Volodymyr, et al.
(författare)
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On the Analytical Representation of Chip Area and Tool Geometry when Oblique Turning with Round Tools. Part 2: Variation of Tool Geometry along the Edge Line
- 2015
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Ingår i: 15th CIRP Conference on Modelling of Machining Operations (15TH CMMO). - : Elsevier BV. - 2212-8271. ; 31, s. 423-428
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Konferensbidrag (refereegranskat)abstract
- This paper presents the models, analytical equations and results of analysis for determination of major cutting edge, orthogonal and normal clearance and rake angles, and cutting edge inclination angle. The analysis is carried for variable side and back rake angles used by the tool manufacturers and a corresponding variation of the geometry along the edge line for the case of round tools. The influence of tool nose radius, chamfer/chipbreaker angle and depth-of-cut was considered as well. Significant variation in orthogonal geometry from that stated in catalogues was found in most cases. The developed analytical solutions and algorithms allow the establishment of fundamental geometrical relationships and giving a correct prediction when developing new tools for conventional and rotary turning. (C) 2015 The Authors. Published by Elsevier B.V.
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| 29. |
- Bushlya, Volodymyr, et al.
(författare)
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Wear mechanisms of uncoated and coated cemented carbide tools in machining lead-free silicon brass
- 2017
-
Ingår i: Wear. - : Elsevier BV. - 0043-1648. ; 376-377, s. 143-151
-
Tidskriftsartikel (refereegranskat)abstract
- Free-machining brass containing 2–3% of lead is a preferred industrial material as it shows excellent machinability where low cutting forces, short chips and reduced tool wear are attained. However this addition of lead, a highly toxic and hazardous material, leads to health and environmental issues. Alternative lead-free brasses are known for poor chip control and accelerated tool wear. The current study focuses on wear mechanisms of uncoated and coated cemented carbide tools when high-speed machining lead-free CuZn21Si3P silicon brass. The study shows that severe crater formation on the rake is the dominant tool failure mode. Microscopy observations indicate the diffusion wear mechanism to be driven by diffusion of cobalt binder into the chips and minor cross-diffusion of copper and zinc. Loss of the binder in cemented carbide is accompanied by adhesive pluck-out of WC grains. As a way to hinder the loss of Co, the diffusion preventing capacity of a-C:H diamond like carbon and (Ti,V,Zr,Nb,Hf,Ta)N nitride coating were tested. SEM, EDX and TEM data show that formation of amorphous SiO2 and stoichiometric β-SiAlON stable layers was observed on the nitride coating, thus preventing diffusional tool wear. O-rich and N-rich glassy amorphous layers in Si-Al-O-N system with ZnS inclusions were found on the DLC coating. Partial delamination of the DLC coating and removal of the glassy phases resulted in localized crater formation associated with diffusional wear.
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| 30. |
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| 31. |
- Carlsson, Jörgen, et al.
(författare)
-
Polypeptides having binding affinity for HER2
- 2003
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Patent (populärvet., debatt m.m.)abstract
- A polypeptide is provided, which has a binding affinity for HER2 and which is related to a domain of staphylococcal protein A (SPA) in that the sequence of the polypeptide corresponds to the sequence of the SPA domain having from 1 to about 20 substitution mutations. Nucleic acid encoding the polypeptide, as well as expression vector and host cell for expressing the nucleic acid, are also provided. Also provided is the use of such a polypeptide as a medicament, and as a targeting agent for directing substances conjugated thereto to cells overexpressing HER2. Methods, and kits for performing the methods, are also provided, which methods and kits rely on the binding of the polypeptide to HER2.
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| 32. |
- Cescon, Marzia, et al.
(författare)
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Short-Term Diabetes Blood Glucose Prediction Based On Blood Glucose Measurements
- 2009
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Konferensbidrag (refereegranskat)abstract
- Given current glucose value, amount and timing of insulin injections and food intake, is it possible to predict future blood glucose levels with a prediction error of ±20 mg/dL? In the current study an attempt is made to empirically model the glucose-insulin dynamic interplay and to provide model-based short-term predictors suitable for the purpose.
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| 33. |
- Cescon, Marzia, et al.
(författare)
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Subspace-Based Model Identification of Diabetic Blood Glucose Dynamics
- 2009
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Ingår i: IFAC Proceedings Volumes. ; 42:10, s. 233-238
-
Tidskriftsartikel (refereegranskat)abstract
- The paper describes an on-line identification algorithm to estimate the steam production of a municipal solid waste incinerator. The algorithm has to learn on-line the system dynamics due to the heavy disturbances acting on the incineration process. The learning algorithm is based on radial basis function networks and combines the growth criterion of the resource allocating network technique with an adaptive extended Kalman filter to update all the parameters of the networks.
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| 34. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
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Characterization of methylation patterns associated with lifestyle factors and vitamin D supplementation in a healthy elderly cohort from Southwest Sweden
- 2022
-
Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways. We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70-95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the solute carrier family 25 (SCL25A24) gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt pathway and general cancer processes. To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D3 can be monitored.
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| 35. |
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| 36. |
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| 37. |
- Ekendahl, S, et al.
(författare)
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Characterization of attached bacterial populations in deep granitic groundwaters from the deep chrystalline bedrock of the Stripa research mine by 16S rRNA gene sequencing and scanning electron microscopy
- 1994
-
Ingår i: Microbiology. - : Society for General Microbiology. - 1350-0872 .- 1465-2080. ; 140, s. 1575-1583
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents the molecular characterization of attached bacterial populations growing in slowly flowing artesian groundwater from deep crystalline bed-rock of the Stripa mine, south central Sweden. Bacteria grew on glass slides in laminar flow reactors connected to the anoxic groundwater flowing up through tubing from two levels of a borehole, 812-820 m and 970-1240 m. The glass slides were collected, the bacterial DNA was extracted and the 16S rRNA genes were amplified by PCR using primers matching universally conserved positions 519-536 and 1392-1405. The resulting PCR fragments were subsequently cloned and sequenced. The sequences were compared with each other and with 16S rRNA gene sequences in the EMBL database. Three major groups of bacteria were found. Signature bases placed the clones in the appropriate systematic groups. All belonged to the proteobacterial groups beta and gamma. One group was found only at the 812-820 m level, where it constituted 63% of the sequenced clones, whereas the second group existed almost exclusively at the 970-1240 m level, where it constituted 83% of the sequenced clones. The third group was equally distributed between the levels. A few other bacteria were also found. None of the 16S rRNA genes from the dominant bacteria showed more than 88% similarity to any of the others, and none of them resembled anything in the database by more than 96%. Temperature did not seem to have any effect on species composition at the deeper level. SEM images showed rods appearing in microcolonies. The conditions at the levels differ in pH, temperature, redox and flow rate, and in content of sulphate, iron and sulphide. The presence of one dominant species in the laminar-flow reactors at each level indicates that the environments might have offered restrictive physical or physiological conditions difficult to adapt to.
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| 38. |
- Ekerljung, Lina, 1980-, et al.
(författare)
-
Generation and Evaluation of Bispecific Affibody Molecules for Simultaneous Targeting of EGFR and HER2
- 2012
-
Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 23:9, s. 1802-1811
-
Tidskriftsartikel (refereegranskat)abstract
- Co-expression of several ErbB receptors has been found in many cancers and has been linked with increased aggressiveness of tumors and a worse patient prognosis. This makes the simultaneous targeting of two surface receptors by using bispecific constructs an increasingly appreciated strategy. Here we have generated six such bispecific targeting proteins, which each comprising two monomeric affibody molecules with specific binding to either of the two human epidermal growth factor receptors, EGFR and HER2, respectively. The bispecific constructs were designed with (i) alternative positioning (N- or C-terminal) of the different affibody molecules, (ii) two alternative peptide linkers (Gly4Ser)3 or (Ser4Gly)3, and (iii) affibody molecules with different affinity (nanomolar or picomolar) for HER2. Using both Biacore technology and cell binding assays it was demonstrated that all six constructs could bind simultaneously to both their target proteins. N-terminal positioning of the monomeric affibody molecules was favorable to promote the binding to respective target. Interestingly, bispecific constructs containing the novel (Ser4Gly)3 linker displayed a higher affinity in cell binding, as compared to constructs containing the more conventional linker, (Gly4Ser)3. It could further be concluded that bispecific constructs (but not the monomeric affibody molecules) induced dimerization and phosphorylation of EGFR in SKBR3 cells, which express fairly high levels of both receptors. It was also investigated whether the bispecific binding would influence cell growth or sensitize cells for ionizing radiation, but no such effects were observed.
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| 39. |
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| 40. |
- Fallqvist, Mikael, 1982-, et al.
(författare)
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Influence of the tool surface micro topography on the tribological characteristics in metal cutting – Part I Experimental observations of contact conditions
- 2013
-
Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 298, s. 87-98
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of surface micro topography of CVD α-Al2O3 coatings, deposited on cemented carbide inserts, on tribological characteristics in sliding contact and in metal cutting has been investigated using quenched and tempered steel as counter/work material. Pin-on-disc and turning tests were carried out and post-test characterization using 3D optical surface profilometry and scanning electron microscopy was performed in order to investigate the tribological response of the coatings. The results show that surface micro topography can have a significant impact on the tribological performance of Al2O3 coatings under initial and cutting contact conditions. For both kinds of tests the tendency for transfer of workpiece material strongly increases with increasing coating micro topography. In the pin-on-disc tests, a smooth coating surface significantly reduces the friction coefficient. In the turning tests the contact conditions at the flank face increase with decreasing micro topography. In contrast, no general conclusions can be drawn regarding the influence of coating micro topography on the contact conditions at the rake face. The resulting topography of the turned surface was found to increase with increasing coating topography.
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| 41. |
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| 42. |
- Fleetwood, Filippa, et al.
(författare)
-
Simultaneous targeting of two ligand-binding sites on VEGFR2 using biparatopic Affibody molecules results in dramatically improved affinity
- 2014
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4, s. 7518-
-
Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis plays an important role in cancer and ophthalmic disorders such as age-related macular degeneration and diabetic retinopathy. The vascular endothelial growth factor (VEGF) family and corresponding receptors are regulators of angiogenesis and have been much investigated as therapeutic targets. The aim of this work was to generate antagonistic VEGFR2-specific affinity proteins having adjustable pharmacokinetic properties allowing for either therapy or molecular imaging. Two antagonistic Affibody molecules that were cross-reactive for human and murine VEGFR2 were selected by phage and bacterial display. Surprisingly, although both binders independently blocked VEGF-A binding, competition assays revealed interaction with non-overlapping epitopes on the receptor. Biparatopic molecules, comprising the two Affibody domains, were hence engineered to potentially increase affinity even further through avidity. Moreover, an albumin-binding domain was included for half-life extension in future in vivo experiments. The best-performing of the biparatopic constructs demonstrated up to 180-fold slower dissociation than the monomers. The new Affibody constructs were also able to specifically target VEGFR2 on human cells, while simultaneously binding to albumin, as well as inhibit VEGF-induced signaling. In summary, we have generated small antagonistic biparatopic Affibody molecules with high affinity for VEGFR2, which have potential for both future therapeutic and diagnostic purposes in angiogenesis-related diseases.
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| 43. |
- Fornebo, Ida, et al.
(författare)
-
Role of antithrombotic therapy in the risk of hematoma recurrence and thromboembolism after chronic subdural hematoma evacuation: a population-based consecutive cohort study.
- 2017
-
Ingår i: Acta neurochirurgica. - : Springer Science and Business Media LLC. - 0942-0940 .- 0001-6268. ; 159:11, s. 2045-2052
-
Tidskriftsartikel (refereegranskat)abstract
- To establish the risk of recurrence in patients with chronic subdural hematoma (cSDH) on antithrombotic treatment (AT, i.e., antiplatelets and anticoagulants). Secondary end points were perioperative morbidity and mortality between groups (AT vs. no-AT group) and exploration if timing of resumption of AT treatment (i.e., prophylactic early vs. late resumption) influenced the occurrence of thromboembolism and hematoma recurrence.In a population-based consecutive cohort, we conducted a retrospective review of 763 patients undergoing primary burr hole procedures for cSDH between January 1, 2005, and December 31, 2010, at the Karolinska University Hospital, Stockholm, Sweden. Early AT resumption was ≤30days and late >30days after the procedure.A total of 308/763 (40.4%) cSDH patients were on AT treatment at the time of diagnosis. There was no difference in cSDH recurrence within 3months (11.0% vs. 12.0%, p=0.69) nor was there any difference in perioperative mortality (4.0% vs. 2.0%, p=0.16) between those using AT compared to those who were not. However, perioperative morbidity was more common in the AT group compared to no-AT group (10.7% vs. 5.1%, p=0.003). Comparing early vs. late AT resumption, there was no difference with respect to recurrence (7.0% vs. 13.9%, p=0.08), but more thromboembolism in the late AT resumption group (2.0% vs. 7.0%, p<0.01).In clinical practice, cSDH patients on AT therapy at the time of diagnosis have similar recurrence rates and mortality compared to those without AT therapy, but with higher morbidity. Early resumption was not associated with more recurrence, but with lower thromboembolic frequency. Early AT resumption seems favorable, and a prospective RCT is needed.
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| 44. |
- Friedman, Mikaela, 1977-
(författare)
-
Affibody molecules targeting the epidermal growth factor receptor for tumor imaging applications
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tumor targeting and molecular imaging of protein markers specific for or overexpressed in tumors can add useful information in deciding upon treatment and assessing the response to treatment for a cancer patient. The epidermal growth factor receptor (EGFR) is one such tumor-associated receptor, which expression is abnormal or upregulated in various cancers and associated with a poor patient prognosis. It is therefore considered a good target for imaging and therapy. Monoclonal antibodies and recently also antibody fragments have been investigated for in vivo medical applications, like therapy and imaging. In molecular imaging a small sized targeting agent is favorable to give high contrast and therefore, antibody fragments and lately also small affinity proteins based on a scaffold structure constitute promising alternatives to monoclonal antibodies. Affbody molecules are such affinity proteins that are developed by combinatorial protein engineering of the 58 amino acid residue Z-domain scaffold, derived from protein A. In this thesis, novel Affibody molecules specific for the EGFR have been selected from a combinatorial library using phage display technology. Affibody molecules with moderate high affinity demonstrated specific binding to native EGFR on the EGFR-expressing epithelial carcinoma A431 cell line. Further cellular assays showed that the EGFR-binding Affibody molecules could be labeled with radiohalogens or radiometals with preserved specific binding to EGFR-expressing cells. In vitro, the Affibody molecule demonstrated a high uptake and good retention to EGFR-expressing cells and was found to internalize. Furthermore, successful imaging of tumors in tumor-bearing mice was demonstrated. Low nanomolar or subnanomolar affinities are considered to be desired for successful molecular imaging and a directed evolution to increase the affinity was thus performed. This resulted in an approximately 30-fold improvement in affinity, yielding EGFR-binding Affibody molecules with KD´s in the 5-10 nM range, and successful targeting of A431 tumors in tumor-bearing mice. To find a suitable format and labeling, monomeric and dimeric forms of one affinity matured binder were labeled with 125I and 111In. The radiometal-labeled monomeric construct, 111In-labeled-ZEGFR:1907, was found to provide the best tumor-to-organ ratio due to good tumor localization and tumor retention. The tumor-to-blood ratio, which is often used as a measure of contrast, was 31±8 at 24 h post injection and the tumor was clearly visualized by gamma-camera imaging. Altogether, the EGFR-binding Affibody molecule is considered a promising candidate for further development of tumor imaging tracers for EGFR-expressing tumors and metastases. This could simplify the stratification of patients for treatment and the assessment of the response of treatment in patients.
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| 45. |
- Friedman, Mikaela, et al.
(författare)
-
Directed evolution to low nanomolar affinity of a tumor-targeting epidermal growth factor receptor-binding affibody molecule
- 2008
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 376:5, s. 1388-1402
-
Tidskriftsartikel (refereegranskat)abstract
- The epidermal growth factor receptor 1 (EGFR) is overexpressed in various malignancies and is associated with a poor patient prognosis. A small, receptor-specific, high-affinity imaging agent would be a useful tool in diagnosing malignant tumors and in deciding upon treatment and assessing the response to treatment. We describe here the affinity maturation procedure for the generation of Affibody molecules binding with high affinity and specificity to EGFR. A library for affinity maturation was constructed by rerandomization of selected positions after the alignment of first-generation binding variants. New binders were selected with phage display technology, using a single oligonucleotide in a single-library effort, and the best second-generation binders had an approximately 30-fold improvement in affinity (K(d)=5-10 nM) for the soluble extracellular domain of EGFR in biospecific interaction analysis using Biacore. The dissociation equilibrium constant, K(d), was also determined for the Affibody with highest affinity using EGFR-expressing A431 cells in flow cytometric analysis (K(d)=2.8 nM). A retained high specificity for EGFR was verified by a dot blot assay showing staining only of EGFR proteins among a panel of serum proteins and other EGFR family member proteins (HER2, HER3, and HER4). The EGFR-binding Affibody molecules were radiolabeled with indium-111, showing specific binding to EGFR-expressing A431 cells and successful targeting of the A431 tumor xenografts with 4-6% injected activity per gram accumulated in the tumor 4 h postinjection.
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| 46. |
- Friedman, Mikaela, et al.
(författare)
-
Engineering and characterization of a bispecific HER2 x EGFR-binding affibody molecule
- 2009
-
Ingår i: Biotechnology and applied biochemistry. - 0885-4513 .- 1470-8744. ; 54, s. 121-131
-
Tidskriftsartikel (refereegranskat)abstract
- HER2 (human epidermal-growth-factor receptor-2; ErbB2) and EGFR (epidermal-growth-factor receptor) are overexpressed in various forms of cancer, and the co-expression of both HER2 and EGFR has been reported in a number of studies. The simultaneous targeting of HER2 and EGFR has been discussed as a strategy with which to potentially increase efficiency and selectivity in molecular imaging and therapy of certain cancers. In an effort to generate a molecule capable of bispecifically targeting HER2 and EGFR, a gene fragment encoding a bivalent HER2-binding affibody molecule was genetically fused in-frame with a bivalent EGFR-binding affibody molecule via a (G(4)S)(3) [(Gly(4)-Ser)(3)]-encoding gene fragment. The encoded 30 kDa affibody construct (Z(HER2))(2)-(G(4)S)(3)-(Z(EGFR))(2), with potential for bs (bispecific) binding to HER2 and EGFR, was expressed in Escherichia coli and characterized in terms of its binding capabilities. The retained ability to bind HER2 and EGFR separately was demonstrated using both biosensor technology and flow-cytometric analysis, the latter using HER2- and EGFR-overexpressing cells. Furthermore, simultaneous binding to HER2 and EGFR was demonstrated in: (i) a sandwich format employing real-time biospecific interaction analysis where the bs affibody molecule bound immobilized EGFR and soluble HER2; (ii) immunofluorescence microscopy, where the bs affibody molecule bound EGFR-overexpressing cells and soluble HER2; and (iii) a cell-cell interaction analysis where the bs affibody molecule bound HER2-overexpressing SKBR-3 cells and EGFR-overexpressing A-431 cells. This is, to our knowledge, the first reported bs affinity protein with potential ability for the simultaneous targeting of HER2 and EGFR. The potential future use of this and similar constructs, capable of bs targeting of receptors to increase the efficacy and selectivity in imaging and therapy, is discussed.
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| 47. |
- Friedman, Mikaela, et al.
(författare)
-
Phage display selection of Affibody molecules with specific binding to the extracellular domain of the epidermal growth factor receptor
- 2007
-
Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 20:4, s. 189-199
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules specific for the epidermal growth factor receptor (EGFR) have been selected by phage display technology from a combinatorial protein library based on the 58-residue, protein A-derived Z domain. EGFR is overexpressed in various malignancies and is frequently associated with poor patient prognosis, and the information provided by targeting this receptor could facilitate both patient diagnostics and treatment. Three selected Affibody variants were shown to selectively bind to the extracellular domain of EGFR (EGFR-ECD). Kinetic biosensor analysis revealed that the three monomeric Affibody molecules bound with similar affinity, ranging from 130 to 185 nM. Head-to-tail dimers of the Affibody molecules were compared for their binding to recombinant EGFR-ECD in biosensor analysis and in human epithelial cancer A431 cells. Although the dimeric Affibody variants were found to bind in a range of 25-50 nM affinities in biosensor analysis, they were found to be low nanomolar binders in the cellular assays. Competition assays using radiolabeled Affibody dimers confirmed specific EGFR-binding and demonstrated that the three Affibody molecules competed for the same epitope. Immunofluorescence microscopy demonstrated that the selected Affibody dimers were initially binding to EGFR at the cell surface of A431, and confocal microscopy analysis showed that the Affibody dimers could thereafter be internalized. The potential use of the described Affibody molecules as targeting agents for radionuclide based imaging applications in various carcinomas is discussed.
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| 48. |
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| 49. |
- Giacomello, Stefania, et al.
(författare)
-
Spatially resolved transcriptome profiling in model plant species
- 2017
-
Ingår i: Nature Plants. - : Springer Science and Business Media LLC. - 2055-026X .- 2055-0278. ; 3:6
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding complex biological systems requires functional characterization of specialized tissue domains. However, existing strategies for generating and analysing high-throughput spatial expression profiles were developed for a limited range of organisms, primarily mammals. Here we present the first available approach to generate and study highresolution, spatially resolved functional profiles in a broad range of model plant systems. Our process includes highthroughput spatial transcriptome profiling followed by spatial gene and pathway analyses. We first demonstrate the feasibility of the technique by generating spatial transcriptome profiles from model angiosperms and gymnosperms microsections. In Arabidopsis thaliana we use the spatial data to identify differences in expression levels of 141 genes and 189 pathways in eight inflorescence tissue domains. Our combined approach of spatial transcriptomics and functional profiling offers a powerful new strategy that can be applied to a broad range of plant species, and is an approach that will be pivotal to answering fundamental questions in developmental and evolutionary biology.
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| 50. |
- Gillsjö, Catharina, Senior Lecturer, 1963-, et al.
(författare)
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Lifestyle's influence on community-dwelling older adults' health : A mixed-methods study design
- 2021
-
Ingår i: Contemporary Clinical Trials Communications. - Amsterdam : Elsevier. - 2451-8654. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Aging often involves health problems and difficulties, such as physical and psychological impairments, isolation, and loneliness, causing social and existential consequences. Studies have explored aging from different perspectives. However, few studies have examined healthy older adults’ genetic backgrounds, lifestyles, and meaning in life separately or in combination. This study aims to describe how healthy older adults experience aging, health, lifestyles, and meaning in life and explore potential genetic correlations.Methods and Design: The project will comprise three main parts: a quantitative section featuring the development and testing of a lifestyle questionnaire, a quantitative genetic analysis, and a qualitative interview study. Participants will be community-dwelling, healthy, older adults between 70 and 95 years of age. A sample size of 800 older adults will be invited to participate in seminars in collaboration with the national Swedish association Active Seniors. Data will be collected through lifestyle questionnaire, DNA extracted from saliva samples, and interviews. Based on questionnaire responses, profile groups will be created and compared statistically with variations in genetic backgrounds, providing the basis for recruiting participants to the qualitative interviews.Discussion: This study's expected outcome will be to gain knowledge about variations in genetic backgrounds correlated with individual experiences regarding aging, health, and meaning in life. This knowledge can improve the understanding of motivations for healthy lifestyle changes. The results can reveal potential implications for individual prerequisites to healthy aging and how health-promoting aging and lifestyle counseling can be adjusted to meet individual needs.
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