| 1. |
- Bahr, Carsten, et al.
(författare)
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A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies
- 2018
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 553:7689, s. 515-520
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies1. Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a ‘super-enhancer’2 is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors. This caused an accumulation of differentiation-arrested multipotent progenitors and loss of myeloid and B cells, mimicking the phenotype caused by Mx1-Cre-mediated conditional deletion of the Myc gene in haematopoietic stem cells3. This super-enhancer comprises multiple enhancer modules with selective activity that recruits a compendium of transcription factors, including GFI1b, RUNX1 and MYB. Analysis of mice carrying deletions of individual enhancer modules suggests that specific Myc expression levels throughout most of the haematopoietic hierarchy are controlled by the combinatorial and additive activity of individual enhancer modules, which collectively function as a ‘blood enhancer cluster’ (BENC). We show that BENC is also essential for the maintenance of MLL–AF9-driven leukaemia in mice. Furthermore, a BENC module, which controls Myc expression in mouse haematopoietic stem cells and progenitors, shows increased chromatin accessibility in human acute myeloid leukaemia stem cells compared to blasts. This difference correlates with MYC expression and patient outcome. We propose that clusters of enhancers, such as BENC, form highly combinatorial systems that allow precise control of gene expression across normal cellular hierarchies and which also can be hijacked in malignancies.
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| 2. |
- Kvisteroy, Terje, et al.
(författare)
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Far infrared low-cost uncooled bolometer for automotive use
- 2007
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Ingår i: Advanced Microsystems for Automotive Applications 2007. - BERLIN : SPRINGER-VERLAG BERLIN. - 9783540713241 ; , s. 265-278
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Konferensbidrag (refereegranskat)abstract
- A proposed EU regulation requires the automotive industry to develop technologies that will substantially decrease the risk for vulnerable road users such as pedestrians when hit by a vehicle. Automatic brake assist systems, activated by a suitable sensor, will reduce the speed of the vehicle before the impact. Far InfraRed (FIR) detectors are ideal candidates for such sensing systems. In order to enable high volume serial installation, the main development must be focused on cost reduction. Optimizing all aspects of the system, including sensor size, production yield and 3D wafer level vacuum packaging will lower today's "high end" FIR product costs by an order of magnitude. A low-cost FIR infrared bolometer is developed in the Eureka labeled PIMS (Pedestrian Injury Mitigation System) project. In the paper the background and the actual design of the first demonstrator to be finished in 2008 are described in detail.
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| 3. |
- Lechman, Eric R, et al.
(författare)
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miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
- 2016
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 29:2, s. 214-228
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Tidskriftsartikel (refereegranskat)abstract
- To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
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| 4. |
- Schijven, Dick, et al.
(författare)
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Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
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Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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| 5. |
- Stanley, Dick, et al.
(författare)
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Extended analyses : finding deep structure in standard high school mathematics
- 2007
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Ingår i: Journal of Mathematics Teacher Education. - : Springer Science and Business Media LLC. - 1386-4416 .- 1573-1820. ; 10:4-6, s. 391-397
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes an approach for pre-service or in-service mathematics education thatteaches sophisticated mathematics using only the tools of high school mathematics. The idea is to start witha standard problem from high school mathematics and let the solution to this problem serve as a platform forasking good mathematical questions and searching for deeper mathematical structure beyond the obvious"answer" to the question. Surprisingly, it turns out that high school mathematics is remarkably open to thissort of analysis, and the results are more interesting mathematically than one might initially think.
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| 6. |
- Vieider, Christian, et al.
(författare)
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Low-cost far infrared bolometer camera for automotive use
- 2007
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Ingår i: P SOC PHOTO-OPT INSTRUM ENG. - : SPIE. - 9780819466648 ; , s. 5421-5421
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Konferensbidrag (refereegranskat)abstract
- A new low-cost long-wavelength infrared bolometer camera system is under development. It is designed for use with an automatic vision algorithm system as a sensor to detect vulnerable road users in traffic. Looking 15 in in front of the vehicle it can in case of an unavoidable impact activate a brake assist system or other deployable protection system. To achieve our cost target below epsilon 100 for the sensor system we evaluate the required performance and can reduce the sensitivity to 150 mK and pixel resolution to 80 x 30. We address all the main cost drivers as sensor size and production yield along with vacuum packaging, optical components and large volume manufacturing technologies. The detector array is based on a new type of high performance thermistor material. Very thin Si/SiGe single crystal multi-layers are grown epitaxially. Due to the resulting valence barriers a high temperature coefficient of resistance is achieved (3.3%/K). Simultaneously, the high quality crystalline material provides very low 1/f-noise characteristics and uniform material properties. The thermistor material is transferred from the original substrate wafer to the read-out circuit using adhesive wafer bonding and subsequent thinning. Bolometer arrays can then be fabricated using industry standard MEMS process and materials. The inherently good detector performance allows us to reduce the vacuum requirement and we can implement wafer level vacuum packaging technology used in established automotive sensor fabrication. The optical design is reduced to a single lens camera. We develop a low cost molding process using a novel chalcogenide glass (GASIR (R) 3) and integrate anti-reflective and anti-erosion properties using diamond like carbon coating.
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