| 1. |
- Andersson, Anna, et al.
(författare)
-
Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations
- 2005
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 19:6, s. 1042-1050
-
Tidskriftsartikel (refereegranskat)abstract
- Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.
|
|
| 2. |
- Andersson, Anna, et al.
(författare)
-
Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status.
- 2007
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 21:6, s. 1198-1203
-
Tidskriftsartikel (refereegranskat)abstract
- Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (40.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.
|
|
| 3. |
- Bergström, Erik, 1976-, et al.
(författare)
-
Erfarenheter, lärdomar och effekter med gränsöverskridande arbete för utbytesstudier
- 2018
-
Ingår i: NU2018 - Det akademiska lärarskapet.
-
Konferensbidrag (refereegranskat)abstract
- I Högskolan i Skövdes (HS) nuvarande utvecklingsplan beskrivs att samtliga utbildningsprogram som ges vid lärosätet skall erbjuda möjligheter till studier utomlands. Som en konsekvens har en strategisk satsning för att stimulera en ökad mobilitet vid HS initierats genom att Institutionen för informationsteknologi (IIT) tillsammans med verksamhetsstödet har deltagit i ett UHR-projekt med fokus på vägledningsprocessen i samband med mobilitet.Projektet har pågått under 18 månader och ett 10-tal deltagare som representerar de flesta roller som är involverade i internationaliseringsarbetet på IIT och verksamhetsstödet har ingått. Projektet har bedrivits främst som en serie av workshoppar där parallell datainsamling har skett med hjälp av intervjuer och enkätstudier.I detta bidrag vill vi visa några av de mål som projektet fokuserat på samt syftet med dessa. Projektet har haft följande mål:Identifiera minst tre partnerlärosäten som passar varje utbildningsprogram - Målet syftar till att kartlägga både existerande och nya partnerlärosäte för att på så sätt sänka tröskeln för studenter som är intresserade av utbyte, men som har svårt att hitta lämpliga alternativ.Tydliggöra roll- och ansvarsfördelning i mobilitetsprocessen - Detta mål syftar till att utforma processbeskrivningar för att tydliggöra roll- och ansvarsfördelning kring utresandeprocessen för programansvarig, ämnesföreträdare, internationell koordinator, studie- och karriärvägledaren, studenten och partnerlärosätet. Även kommunikationsaspekter och studentperspektiv beaktas i detta mål.Skapa adekvat vägledning och informationsinsatser gentemot studenterna - Syftet med målet är att utveckla, strukturera och systematisera informationsvägar och kommunikation mellan vägledning, programansvarig, partnerlärosäte och studenter.Identifiera och utvärdera nyckelfaktorerna för att förbättra stödet till studenterna, undanröja hinder i mobilitetsprocessen samt underlätta programansvarigas och studie- och karriärvägledarnas arbete med utresande studenter - Målet är att identifiera och utvärdera nyckelfaktorer som hindrar mobilitet som kan spridas internt på HS samt externt för att i förlängningen öka mobiliteten bland Sveriges studenter.Se till att samtliga kandidatprogram på IIT har en termin avsatt för utlandsstudier och undanröja de hinder som finns i befintliga programstrukturer - Syftet är att göra det enklare för studenter att under sin ordinarie studietid genomföra utbytesstudier utan att deras studier vid HS blir drabbade av förkunskapsstrukturer som hindrar fortsatta studier vid hemkomst.I studien inkludera de studenter som har varit intresserade eller sökt utbytesstudier men som inte kommit iväg på utbyte - Syftet är att skapa en god översikt över vilka skäl denna studentkategori har haft för att avstå utbytesstudier för att på så vis kunna förbättra existerande processer för utbytesstudier och därmed minimera risken att intresserade studenter väljer att avstå från utbytesstudier.Vid projektets avslut analyserades projektets direkta och indirekta interorganisatoriska effekter tillsammans med aktuell statistik för de studenter som under 2017 nominerats för utbytesstudier. En uppenbar effekt av projektets arbete är att antalet studenter som 2017 vid IIT nominerats för utbytesstudier ökat kraftigt. Likaså observeras ökade kunskaper om processen kring utbytesstudier och ett förbättrat studentperspektiv och bättre kunskaper om studenternas upplevelse av nomineringsprocessen.Under presentation vill vi visa upp fler detaljer från vår analys samt hur vi planerar att arbeta vidare med de resultat vi fått fram i projektet.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Damstra, Alyt, et al.
(författare)
-
Knowledge and the News: An Investigation of the Relation Between News Use, News Avoidance, and the Presence of (Mis)beliefs
- 2023
-
Ingår i: The International Journal of Press/Politics. - : SAGE Publications. - 1940-1612 .- 1940-1620. ; 28:1, s. 29-48
-
Tidskriftsartikel (refereegranskat)abstract
- While increasing scholarly attention has been devoted to news avoidance, there are only few studies taking the distinction between intentional and unintentional news avoidance into consideration, and none that has investigated the linkage between the two types of news avoidance and knowledge about politics and society. To fill this void, this study explores this relationship while distinguishing between knowledge related to uncontested issues and knowledge related to issues that have been subject to public controversies (climate change, vaccination, genetically modified organisms, crime, and immigration). Relying on a large-scale survey among Swedish citizens conducted in 2020 (N = 2,160), we find that the relationship with patterns of news use is substantially different across these types of beliefs. Among other things, the results suggest that knowledge of uncontested issue domains is positively related to news use, but knowledge of contested issue domains is not. The intentional avoidance of news is only negatively related to knowledge of contested issues. Taken together, the results suggest that the mechanisms driving beliefs related to uncontested versus contested issues are substantially different.
|
|
| 7. |
|
|
| 8. |
- Damstra, Alyt, et al.
(författare)
-
What does fake look like? A review of the literature on intentional deception in the news and on social media
- 2021
-
Ingår i: Journalism Studies. - 1461-670X. ; 22:14, s. 1947-1963
-
Tidskriftsartikel (refereegranskat)abstract
- This paper focuses on the content features of intentional deceptive information in the news (i.e., fake news) and on social media. Based on an extensive review of relevant literature (i.e., political journalism and communication, computational linguistics), we take stock of existing knowledge and present an overview of the structural characteristics that are indicative of intentionally deceptive information. We discuss the strength of underlying empirical evidence and identify underdeveloped areas of research. With this paper, we aim to contribute to the systematic study of intentional deception in the news and on social media and to help setting up new lines of research in which intentionally deceptive news items can be operationalized in consistent ways.
|
|
| 9. |
- Draxler, Joar
(författare)
-
Modeling and Simulation of Weld Hot Cracking
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several alloy systems are susceptible to weld hot cracking. Weld hot cracking occurs by fracture of liquid films, normally grain boundary liquid films, at the late stage of the solidification of the weld. The cracks can be small and therefore difficult to detect by nondestructive test methods. If hot cracks are not repaired, they can act as sites for initiation of fatigue and stress corrosion cracking, which in turn can lead to catastrophic failure in critical applications such as aerospace engines and nuclear power plants. Therefore, it is of highest importance to design weld processes so that hot cracking can be avoided. Here, numerical simulation can be a powerful tool for optimizing weld speed, heat input, weld path geometry, weld path sequences, weld fixturing, etc., such that the risk for hot cracking can be minimized. In this thesis, we propose a modeling approach for simulating weld hot cracking in sheet metals with low welding speeds and fully penetrating welds. These conditions are assumed to give rise to isolated grain boundary liquid films (GBLFs) whose crack susceptibility can be analyzed using one-dimensional models. The work is divided into four journal papers. The three first papers treat hot cracking that occurs in the fusion zone of the weld while the last paper treats hot cracking in the partially melted zone of the weld. The main content of the four papers are summarized below. In paper A, a pore-based crack criterion for hot cracking has been developed. This criterion states that cracking occurs in a GBLF if the liquid pressure in the film goes below a fracture pressure. The fracture pressure is determined from a pore model as the liquid pressure that is required to balance the surface tension of an axisymmetric pore in a liquid film located between two parallel plates at a given critical pore radius. The fracture pressure depends on the surface tension, the spacing between the parallel plates and the gas concentration in the liquid. In order to evaluate the above pore-based crack criterion in a GBLF the liquid pressure in the film most be known. In paper B, a one-dimensional GBLF pressure model for a columnar dendritic microstructure has been developed. This model is based on a combination of Poiseuille parallel plate flow and Darcy porous flow. Flow induced by mechanical straining of the GBLF is accounted for by a macroscopic mechanical strain field that is localized to the GBLF by a temperature dependent length scale. In paper C, a computational welding mechanics model for a Varestraint test is developed. The model is used to calibrate the crack criterion in paper A and the pressure model in paper B. It is then used to test the crack criterion in Varestraint tests with different augmented strains. Calculated crack locations, orientations, and widths are shown to correlate well to the experimental Varestraint tests. vii Finally, in paper D, a segregation model for predicting the thickness of eutectic bands has been developed. The thickness of eutectic bands affects the degree of liquation in partially melted zone, and therefore is an important factor for hot cracking in this region of the weld.
|
|
| 10. |
- Folkersen, Lasse, et al.
(författare)
-
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
-
Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
|
|
