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| 2. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 3. |
- Karlsson, Göran, et al.
(författare)
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The Tetraspanin CD9 Affords High-Purity Capture of All Murine Hematopoietic Stem Cells
- 2013
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 4:4, s. 642-648
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Tidskriftsartikel (refereegranskat)abstract
- Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify the cell surface antigen CD9 as a positive marker that provides a simple alternative for hematopoietic stem cell isolation at high purity. Crucially, CD9 affords the capture of all hematopoietic stem cells in murine bone marrow in the absence of contaminating populations that lack authentic stem cell function. Using CD9 as a tool to subdivide hematopoietic stem-cell-containing populations, we provide evidence for heterogeneity at the cellular, functional, and molecular levels.
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| 4. |
- Kyriakidis, Miltos, et al.
(författare)
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A human factors perspective on automated driving
- 2017
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Ingår i: Theoretical Issues in Ergonomics Science. - : Taylor and Francis Ltd.. - 1463-922X .- 1464-536X. ; , s. 1-27
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Tidskriftsartikel (refereegranskat)abstract
- Automated driving can fundamentally change road transportation and improve quality of life. However, at present, the role of humans in automated vehicles (AVs) is not clearly established. Interviews were conducted in April and May 2015 with 12 expert researchers in the field of human factors (HFs) of automated driving to identify commonalities and distinctive perspectives regarding HF challenges in the development of AVs. The experts indicated that an AV up to SAE Level 4 should inform its driver about the AV's capabilities and operational status, and ensure safety while changing between automated and manual modes. HF research should particularly address interactions between AVs, human drivers and vulnerable road users. Additionally, driver-training programmes may have to be modified to ensure that humans are capable of using AVs. Finally, a reflection on the interviews is provided, showing discordance between the interviewees’ statements – which appear to be in line with a long history of HFs research – and the rapid development of automation technology. We expect our perspective to be instrumental for stakeholders involved in AV development and instructive to other parties.
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| 5. |
- Leist, Marcel, et al.
(författare)
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Adverse outcome pathways : opportunities, limitations and open questions
- 2017
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 91:11, s. 3477-3505
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Tidskriftsartikel (refereegranskat)abstract
- Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event erelationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.
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| 6. |
- Tabone, Wilbert, et al.
(författare)
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Vulnerable road users and the coming wave of automated vehicles: Expert perspectives
- 2021
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Ingår i: Transportation Research Interdisciplinary Perspectives. - : Elsevier BV. - 2590-1982. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Automated driving research over the past decades has mostly focused on highway environments. Recent technological developments have drawn researchers and manufacturers to look ahead at introducing automated driving in cities. The current position paper examines this challenge from the viewpoint of scientific experts. Sixteen Human Factors researchers were interviewed about their personal perspectives on automated vehicles (AVs) and the interaction with VRUs in the future urban environment. Aspects such as smart infrastructure, external human-machine interfaces (eHMIs), and the potential of augmented reality (AR) were addressed during the interviews. The interviews showed that the researchers believed that fully autonomous vehicles will not be introduced in the coming decades and that intermediate levels of automation, specific AV services, or shared control will be used instead. The researchers foresaw a large role of smart infrastructure and expressed a need for AV-VRU segregation, but were concerned about corresponding costs and maintenance requirements. The majority indicated that eHMIs will enhance future AV-VRU interaction, but they noted that implicit communication will remain dominant and advised against text-based and instructive eHMIs. AR was commended for its potential in assisting VRUs, but given the technological challenges, its use, for the time being, was believed to be limited to scientific experiments. The present expert perspectives may be instrumental to various stakeholders and researchers concerned with the relationship between VRUs and AVs in future urban traffic.
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| 7. |
- Wray, Jason P., et al.
(författare)
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Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The ETV6-RUNX1 onco-fusion arises in utero, initiating a clinically silent pre-leukemic state associated with the development of pediatric B-acute lymphoblastic leukemia (B-ALL). We characterize the ETV6-RUNX1 regulome by integrating chromatin immunoprecipitation- and RNA-sequencing and show that ETV6-RUNX1 functions primarily through competition for RUNX1 binding sites and transcriptional repression. In pre-leukemia, this results in ETV6-RUNX1 antagonization of cell cycle regulation by RUNX1 as evidenced by mass cytometry analysis of B-lineage cells derived from ETV6-RUNX1 knock-in human pluripotent stem cells. In frank leukemia, knockdown of RUNX1 or its co-factor CBFβ results in cell death suggesting sustained requirement for RUNX1 activity which is recapitulated by chemical perturbation using an allosteric CBFβ-inhibitor. Strikingly, we show that RUNX1 addiction extends to other genetic subtypes of pediatric B-ALL and also adult disease. Importantly, inhibition of RUNX1 activity spares normal hematopoiesis. Our results suggest that chemical intervention in the RUNX1 program may provide a therapeutic opportunity in ALL.
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