| 1. |
- Aamodt, K., et al.
(författare)
-
The ALICE experiment at the CERN LHC
- 2008
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
-
Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
|
|
| 2. |
- Buitenhuis, M, et al.
(författare)
-
Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2
- 2005
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 105:11, s. 4272-4281
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibitor of DNA binding (Id) proteins function as inhibitors of members of the basic helix-loop-helix family of transcription factors and have been demonstrated to play an important role in regulating lymphopoiesis. However, the role of these proteins in regulation of myelopoiesis is currently unclear. In this study, we have investigated the role of Id1 and Id2 in the regulation of granulopoiesis. Id1 expression was initially upregulated during early granulopoiesis, which was then followed by a decrease in expression during final maturation. In contrast, Id2 expression was up-regulated in terminally differentiated granulocytes. In order to determine whether Id expression plays a critical role in regulating granulopoiesis, Id1 and Id2 were ectopically expressed in CD34(+) cells by retroviral transduction. Our experiments demonstrate that constitutive expression of Id1 inhibits eosinophil development, whereas in contrast neutrophil differentiation was modestly enhanced. Constitutive Id2 expression accelerates final maturation of both eosinophils and neutrophils, whereas inhibition of Id2 expression blocks differentiation of both lineages. Transplantation of beta 2-microglobulin(-/-) nonobese diabetic severe combined immunodeficient (NOD/SCID) mice with CD34(+) cells ectopically expressing Id1 resulted in enhanced neutrophil development, whereas ectopic expression of Id2 induced both eosinophil and neutrophil development. These data demonstrate that both Id1 and Id2 play a critical, although differential role in granulopolesis.
|
|
| 3. |
- Buitenhuis, Miranda, et al.
(författare)
-
Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 111:1, s. 112-121
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoiesis is a highly regulated process resulting in the formation of all blood lineages. Aberrant regulation of phosphatidylinositol-3-kinase (PI3K) signaling has been observed in hematopoietic malignancies, suggesting that regulated PI3K signaling is critical for regulation of blood cell production. An ex vivo differentiation system was used to investigate the role of PI3K and its downstream effector, protein kinase B (PKB/c-akt) in myelopoiesis. PI3K activity was essential for hematopoietic progenitor survival. High PKB activity was found to promote neutrophil and monocyte development, while, conversely, reduction of PKB activity was required to induce optimal eosinophil differentiation. In addition, transplantation of beta2-microglobulin (-/-) NOD/SCID mice with CD34(+) cells ectopically expressing constitutively active PKB resulted in enhanced neutrophil and monocyte development, whereas ectopic expression of dominant-negative PKB induced eosinophil development in vivo. Inhibitory phosphorylation of C/EBPalpha on Thr222/226 was abrogated upon PKB activation in hematopoietic progenitors. Ectopic expression of a nonphosphorylatable C/EBPalpha mutant inhibited eosinophil differentiation ex vivo, whereas neutrophil development was induced, demonstrating the importance of PKB-mediated C/EBPalpha phosphorylation in regulation of granulopoiesis. These results identify an important novel role for PKB in regulation of cell fate choices during hematopoietic lineage commitment.
|
|
| 4. |
- Castor, Anders, et al.
(författare)
-
Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
- 2005
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 11:6, s. 630-637
-
Tidskriftsartikel (refereegranskat)abstract
- The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.
|
|
| 5. |
- Castor, Anders, et al.
(författare)
-
Mycket svåra beslut
- 2008
-
Ingår i: Risk & Risici. - 9789157805188 ; , s. 231-248
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 6. |
- Castor, Anders
(författare)
-
Stem and progenitor cell involvement in acute lymphoblastic leukemia
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Leukemic stem cells (LSCs) share the capacity of self renewal and extensive proliferation with normal hematopoietic stem cells (HSCs), and are therefore obvious targets for therapy. As such, they need to be identified and characterized in order to elucidate what drives them, and what separates them from their normal counterparts. The focus of this thesis is on pre B cell Acute Lymphoblastic Leukemia (ALL), the most common form of cancer in children. We have investigated 2 distinct subtypes of ALL, characterized by the gene fusions ETV6-RUNX1 (found mainly in pediatric ALL, conferring a favorable prognosis) and BCR-ABL1 (producing two different onco-proteins, designated P190 and P210, both of which are associated with a poor prognosis in both children and adults). We show that ETV6-RUNX1 ALL are propagated by B-cell committed LSCs expressing the lymphoid marker CD19, leaving the normal HSC compartment intact. In BCR-ABL1-positive ALL we show an unexpected difference between the two forms of the fusion protein, such that the LSC in P190 BCR-ABL1 ALL, similar to ETV6-RUNX1 ALL, are B-cell committed progenitors, whereas P210 BCR-ABL1 ALL originates in a multipotent HSC, expressing the same phenotypical markers as the normal HSC, and with a retained, albeit severely reduced, capacity to produce a clonal myeloid progeny. Interestingly, the LSC still displays the B cell commitment marker CD19, as only CD19+ cells propagates the disease in immunocompromised mice. We cannot, however, exclude very rare, and/or very quiscent CD19-ve P210 LSCs. This represents a hitherto unanticipated distinct biological difference between P190 and P210 ALLs, possibly indicating different requirements for eradication. In the second paper we describe a method to prospectively purify a large part of the leukemic cells from bone marrow or peripheral blood from patients with ALL, for relevant comparisons across samples. We compared ALL cells harvested from bone marrow and peripheral blood from the same patient by gene expression profiling, and found a striking similarity between cells from the two locations, indicating that bone marrow derived biological cues necessary for normal pre B cells not seem to segregate ALL cells in a blood and a bone marrow compartment, and that cells thus can be harvested from either compartment for further gene expression analyses. Finally, in the discussion part of the two papers, are preliminary data from follow up studies discussed, where we find indications for the existence of distinct sets of LSCs within the same patient with ALL or chronic myeloid leukemia in lymphoid blast crisis, contrary to the generally held view of a homogeneous LSC population.
|
|
| 7. |
- Castor, Martin, 1972-
(författare)
-
The use of structural equation modeling to describe the effect of operator functional state on air-to-air engagement outcomes
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Computational evidence of the operative usefulness of a new system is crucial in large system development processes concerning billions of euros or dollars. Although it is obvious that the human often is the most important and critical component of many systems, it has often been hard for Human Factors researchers to express human aspects in a computational and strict way. The thesis describes, through data based statistical modeling, how the concepts or constructs of sensor effectiveness, usability of information, mental workload, situation awareness and teamwork relates to each other and to the operative performance in a fourship of fighter pilots. Through the use of structural equation modeling, ad modum LISREL, a statistical model that describes how the operators’ functional state mediates the effects between technical system oriented variables, was developed.The constructs used in the modeling process have received widespread scientific and operational attention. They have also been identified as multi-dimensional. Many different ways of measuring them have been developed in the scientific community, and the thesis focuses on the next step, i.e. how do these higher order constructs relate to each other in something as multi-dimensional as human activity in real situations?A comprehensive human factors related dataset was collected in a large simulation based acquisition study that examined the requirements and properties of aircraft radar systems. The dataset contains 308 simulated engagements with data from four pilots each, i.e. 1232 cases in a database with 24 variables, generated by 37 pilots. The collected data and the resulting models thus summarizes more than 700 hours of experienced pilots’ complex behavior in an operationally valid environment, and in a way that is of theoretical interest as well as of importance in system development processes. The data thus comes from a real world study of complex processes in a dynamic context, although from a simulator. The thesis is a case example of modern ecologically valid experimental psychology. The data collection does not represent a classical experimental setup, but instead demonstrates methodological needs and considerations for human factors practitioners when working in system development studies. The fact that parts of the used data are classified has not affected the models and scientific conclusions, although the practical findings have been partly circumscribed in the presentation.As a result of the statistical modeling effort, a structural equation model of how the chosen constructs relate to each other, and mediate effects between technical measures by a model of the operator, is proposed. Simplicity of the model was the goal, and based on former experiences and findings, a simplex structure was hypothesized. The final model shows that the covariances between the 24 measures can be explained by a quasi-simplex structure of seven factors.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
