| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Kueppers, Michael, et al.
(författare)
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Triple F-a comet nucleus sample return mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 809-847
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Tidskriftsartikel (refereegranskat)abstract
- The Triple F (Fresh From the Fridge) mission, a Comet Nucleus Sample Return, has been proposed to ESA's Cosmic Vision program. A sample return from a comet enables us to reach the ultimate goal of cometary research. Since comets are the least processed bodies in the solar system, the proposal goes far beyond cometary science topics (like the explanation of cometary activity) and delivers invaluable information about the formation of the solar system and the interstellar molecular cloud from which it formed. The proposed mission would extract three sample cores of the upper 50 cm from three locations on a cometary nucleus and return them cooled to Earth for analysis in the laboratory. The simple mission concept with a touch-and-go sampling by a single spacecraft was proposed as an M-class mission in collaboration with the Russian space agency ROSCOSMOS.
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| 3. |
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| 4. |
- Fynbo, H. O. U., et al.
(författare)
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Revised rates for the stellar triple-alpha process from measurement of C-12 nuclear resonances
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687 .- 1476-4679. ; 433:7022, s. 136-139
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Tidskriftsartikel (refereegranskat)abstract
- In the centres of stars where the temperature is high enough, three alpha-particles (helium nuclei) are able to combine to form C-12 because of a resonant reaction leading to a nuclear excited state(1). (Stars with masses greater than similar to0.5 times that of the Sun will at some point in their lives have a central temperature high enough for this reaction to proceed.) Although the reaction rate is of critical significance for determining elemental abundances in the Universe(1), and for determining the size of the iron core of a star just before it goes supernova(2), it has hitherto been insufficiently determined(2). Here we report a measurement of the inverse process, where a C-12 nucleus decays to three alpha-particles. We find a dominant resonance at an energy of similar to11 MeV, but do not confirm the presence of a resonance at 9.1 MeV (ref. 3). We show that interference between two resonances has important effects on our measured spectrum. Using these data, we calculate the triple-a rate for temperatures from 10(7) K to 10(10) K and find significant deviations from the standard rates(3). Our rate below similar to5 x 10(7) K is higher than the previous standard, implying that the critical amounts of carbon that catalysed hydrogen burning in the first stars are produced twice as fast as previously believed(4). At temperatures above 10(9) K, our rate is much less, which modifies predicted nucleosynthesis in supernovae(5,6).
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| 5. |
- Ruchowska, E., et al.
(författare)
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Nuclear structure of Th-229
- 2006
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Ingår i: Physical Review C. Nuclear Physics. - : American Physical Society. - 0556-2813 .- 1089-490X. ; 73:4
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of excited states in Th-229, populated in the beta decay of Ac-229, have been measured using the advanced time-delayed beta gamma gamma(t) method. Half-lives of 14 states have been determined including 11 of them for the first time. Twenty-seven new gamma lines have been introduced into the beta-decay scheme of Ac-229 based on results of gamma gamma coincidence measurements. Reduced transition probabilities have been determined for more than 70 gamma transitions in Th-229. Average parallel to D-0 parallel to values of 0.029(1), 0.077(3), and 0.024(5) e fm have been deduced for the lowest K-pi=1/2(+/-),3/2(+/-), and 5/2(+/-) parity partner bands, respectively. Excited states in Th-229 and experimental transition rates have been interpreted within the quasiparticle-plus-phonon model. The half-life of the 3.5-eV, 3/2(+) isomeric state is predicted to be about 10 h. Potential energy surfaces on the (beta(2),beta(3)) plane for the lowest single quasiparticle configurations in Th-229 have been calculated using the Strutinsky method.
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| 6. |
- Bhattacharya, Deepta, et al.
(författare)
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Niche recycling through division-independent egress of hematopoietic stem cells
- 2009
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 114:22, s. 37-37
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning. To explain this apparent paradox, we calculated, through cell surface phenotyping and transplantation of unfractionated blood, that similar to 1-5% of the total pool of HSCs enters into the circulation each day. Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches. Consistent with this, repetitive daily transplantations of small numbers of HSCs administered as new niches became available over the course of 7 d led to significantly higher levels of engraftment than did large, single-bolus transplantations of the same total number of HSCs. These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress.
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| 7. |
- Bhattacharya, Deepta, et al.
(författare)
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Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning
- 2006
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 203:1, s. 73-85
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Tidskriftsartikel (refereegranskat)abstract
- In the absence of irradiation or other cytoreductive conditioning, endogenous hematopoietic stem cells (HSCs) are thought to fill the unique niches within the bone marrow that allow maintenance of full hematopoietic potential and thus prevent productive engraftment of transplanted donor HSCs. By transplantation of purified exogenous HSCs into unconditioned congenic histocompatible strains of mice, we show that approximately 0.1-1.0% of these HSC niches are available for engraftment at any given point and find no evidence that endogenous HSCs can be displaced from the niches they occupy. We demonstrate that productive engraftment of HSCs within these empty niches is inhibited by host CD4+ T cells that recognize very subtle minor histocompatibility differences. Strikingly, transplantation of purified HSCs into a panel of severe combined immunodeficient (SCID) mice leads to a rapid and complete rescue of lymphoid deficiencies through engraftment of these very rare niches and expansion of donor lymphoid progenitors. We further demonstrate that transient antibody-mediated depletion of CD4+ T cells allows short-term HSC engraftment and regeneration of B cells in a mouse model of B(-) non-SCID. These experiments provide a general mechanism by which transplanted HSCs can correct hematopoietic deficiencies without any host conditioning or with only highly specific and transient lymphoablation.
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| 8. |
- Bryder, David, et al.
(författare)
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Hematopoietic stem cells: the paradigmatic tissue-specific stem cell
- 2006
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 169:2, s. 338-346
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Tidskriftsartikel (refereegranskat)abstract
- The recent prospective isolation of a wide variety of somatically derived stem cells has affirmed the notion that homeostatic maintenance of most tissues and organs is mediated by tissue-specific stem and progenitor cells and fueled enthusiasm for the use of such cells in strategies aimed at repairing or replacing damaged, diseased, or genetically deficient tissues and organs. Hematopoietic stem cells (HSCs) are arguably the most well-characterized tissue-specific stem cell, with decades of basic research and clinical application providing not only a profound understanding of the principles of stem cell biology, but also of its potential pitfalls. It is our belief that emerging stem cell fields can benefit greatly from an understanding of the lessons learned from the study of HSCs. In this review we discuss some general concepts regarding stem cell biology learned from the study of HSCs with a highlight on recent work pertaining to emerging topics of interest for stem cell biology.
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| 9. |
- Fritioff, T., et al.
(författare)
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Purification of radioactive neutron-rich argon beams using an ion source in charge breeding mode
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576 .- 0167-5087. ; 556:1, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of nuclear properties of some neutron-rich asymmetric fission isotopes at an ISOL laboratory present a severe problem when a plasma ion source is used as the primary ion-source. The problem is associated with intense multi-charged symmetric fission contaminants that cannot be mass-separated from asymmetric fission products. In this work we demonstrate how this problem can be overcome on-line by using an electron cyclotron resonance ion source (ECRIS) as a charge-breeding secondary ion-source. Mixed Ar+/Kr2+/Xe3+ radioactive beams from an plasma ion-source were injected into the PHOENIX ECRIS that currently is installed at the ISOLDE facility at CERN in order to improve the ratio of Ar to the background contaminants of Kr and Xe. The signal to noise ratio was improved by more than two orders of magnitude after charge-breeding and mass-separation of the Ar8+, Ar9+ beams. The information on the decay of the Ar-48 nucleus obtained in these tests is useful for a better understanding of the origin of the Ca-48/Ca-46 meteorite isotopic anomaly. Potential applications of the method are discussed.
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| 10. |
- Pronk, Cornelis J. H., et al.
(författare)
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Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy
- 2007
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Ingår i: Cell Stem Cell. - : Elsevier (Cell Press). - 1934-5909 .- 1875-9777. ; 1:4, s. 428-442
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Tidskriftsartikel (refereegranskat)abstract
- The major myeloid blood cell lineages are generated from hematopoietic stem cells by differentiation through a series of increasingly committed progenitor cells. Precise characterization of intermediate progenitors is important for understanding fundamental differentiation processes and a variety of disease states, including leukemia. Here, we evaluated the functional in vitro and in vivo potentials of a range of prospectively isolated myeloid precursors with differential expression of CD150, Endoglin, and CD41. Our studies revealed a hierarchy of myeloerythroid progenitors with distinct lineage potentials. The global gene expression signatures of these subsets were consistent with their functional capacities, and hierarchical clustering analysis suggested likely lineage relationships. These studies provide valuable tools for understanding myeloid lineage commitment, including isolation of an early erythroid-restricted precursor, and add to existing models of hematopoietic differentiation by suggesting that progenitors of the innate and adaptive immune system can separate late, following the divergence of megakaryocytic/erythroid potential.
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