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| 2. |
- van Es, Michael A, et al.
(författare)
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Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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| 3. |
- Zhou, Jianbiao, et al.
(författare)
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Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01.
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:5, s. 1607-11
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Tidskriftsartikel (refereegranskat)abstract
- In a prospective trial in 284 children with B-lineage acute lymphoblastic leukemia (ALL), we assessed the clinical utility of real-time quantitative polymerase chain reaction analysis of antigen receptor gene rearrangements for detection of minimal residual disease (MRD) to identify children at high risk of relapse. At the end of induction therapy, the 5-year risk of relapse was 5% in 176 children with no detectable MRD and 44% in 108 children with detectable MRD (P < .001), with a linear association of the level of MRD and subsequent relapse. Recursive partitioning and clinical characteristics identified that the optimal cutoff level of MRD to predict outcome was 10(-3). The 5-year risk of relapse was 12% for children with MRD less than one leukemia cell per 10(3) normal cells (low MRD) but 72% for children with MRD levels greater than this level (high MRD) (P < .001) and children with high MRD had a 10.5-fold greater risk of relapse. Based upon these results we have altered our treatment regimen for children with B-lineage ALL and children with MRD levels greater than or equal to 10(-3) at the end of 4 weeks of multiagent induction chemotherapy now receive intensified treatment to attempt to decrease their risk of subsequent relapse.
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| 4. |
- Blomberg, C, et al.
(författare)
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Pattern of Accessory Regions and Invasive Disease Potential in Streptococcus pneumoniae.
- 2009
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 199, s. 1032-1042
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Tidskriftsartikel (refereegranskat)abstract
- Background. The invasive disease potential (IDP) of Streptococcus pneumoniae differs between serotypes, but the reason for this is unknown. Methods. A total of 47 pneumococcal isolates from 13 serotypes with different IDPs in humans that belonged to 37 multilocus sequence types were compared by whole genome microarrays and mutant analyses. Results. Approximately 34% of the genes were variable, including 95 genes previously shown by signature-tagged mutagenesis (STM) to be required for invasive disease in mice. Many variable genes were localized to 41 accessory regions (ARs), of which 24 contained genes previously identified by STM as required for invasive disease. Only AR6 and AR34 were preferentially found in isolates of serotypes with high IDPs. Neither AR6, which carries a gene previously identified by STM as required for invasive disease and encodes a 6-phospho-beta glucosidase, nor the putative adhesin expressed by AR34 was required for mouse virulence in TIGR4. Conclusions. Pneumococci possess a repertoire of ARs that differ between clones and even between isolates of the same clone. The ARs required for invasive disease in humans may be redundant, as no unique pattern distinguished the most invasive clones from others. The ARs that contained genes previously identified by STM as required for virulence in mice were frequently absent from invasive human isolates. Only 1 AR (AR6) was present in almost all isolates from the serotypes with the highest IDP (1, 4, and 7F), whereas it was missing from many others.
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| 5. |
- Dahlberg, Björn E. J.
(författare)
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A discrete four vertex theorem
- 2008
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Ingår i: Geometriae Dedicata. - : Springer Science and Business Media LLC. - 0046-5755 .- 1572-9168. ; 133:1, s. 111-128
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Tidskriftsartikel (refereegranskat)abstract
- A discrete four vertex theorem is proved for a general plane polygon using a method of proof that also yields a proof, that appears to be new, for the classical four vertex theorem.
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| 6. |
- Dahlberg, Björn E. J.
(författare)
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The converse of the four vertex theorem
- 2005
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Ingår i: Proceedings of the American Mathematical Society. - 0002-9939 .- 1088-6826. ; 133:7, s. 2131-2135
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Tidskriftsartikel (refereegranskat)abstract
- We establish the converse to the four vertex theorem without the positivity condition.
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| 7. |
- Dahlberg, Björn E. J.
(författare)
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Total curvature and rearrangements.
- 2005
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Ingår i: Arkiv för matematik. - 0004-2080 .- 1871-2487. ; 43:2, s. 323-345
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Tidskriftsartikel (refereegranskat)abstract
- We study to what extent rearrangements preserve the integrability properties of higher order derivatives. It is well known that the second order derivatives of the rearrangement of a smooth function are not necessarily inL 1. We obtain a substitute for this fact. This is done by showing that the total curvature for the graph of the rearrangement of a function is bounded by the total curvature for the graph of the function itself.
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| 8. |
- Dahlberg, E., et al.
(författare)
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The dynamic rollover threshold - a heavy truck sensitivity study
- 2006
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Ingår i: International Journal of Vehicle Design. - 0143-3369 .- 1741-5314. ; 40:03-jan, s. 228-250
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of rollover mechanics, which is required in heavy truck development, commonly relies on a static analysis, providing the steady-state rollover threshold, SSRT. In a rolling vehicle, kinetic energy is always present and that deteriorates the analysis of roll stability from SSRT and implies the need for a dynamic rollover threshold, DRT as a complement. A method to determine DRT is presented and a parameter sensitivity study The influences on SSRT and DRT, including interaction effects, from roll stiffnesses and roll centre heights, are calculated. Results show that a rigid truck and a tractor semitrailer combination are unequally sensitive to parameter changes. Design changes can hence affect SSRT and DRT differently, which indicates that two vehicles can be equally stable statically but differently dynamically. Therefore, if DRT is not analysed, a redesign of a vehicle can deteriorate roll stability even though it appears to improve it.
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| 9. |
- Dehlin, Mats, 1968, et al.
(författare)
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Intra-articular fms-like tyrosine kinase 3 ligand expression is a driving force in induction and progression of arthritis.
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). CONCLUSIONS/SIGNIFICANCE: Our findings indicate that Flt3-L is strongly expressed at the site of inflammation in human RA. It exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. Owing to these properties, treatment attempts to neutralize this molecule should be considered in RA.
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| 10. |
- Drakenberg, Olof, 1964, et al.
(författare)
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Greening Development Planning: A review of country case studies for making the economic case for improved management of environment and natural resources : OECD Environment Working Papers, No. 5
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Different approaches to making the economic case for improved management of natural capital in national planning are reviewed in this report. In many low-income countries natural resources sectors (agriculture, mining, forestry, fishery, nature-based tourism) are identified as the engines of economic growth. However, a majority of the ecosystems on which human well-being depends are being degraded. The difficulties in providing economic and policy-relevant information about sustainable economic management of natural capital are often seen as an important reason for inadequate integration of the environment in macroeconomic and sector polices. The report concludes that the analysed country studies (Lao People's Democratic Republic, Mozambique, Peru, Tajikistan and Uganda) mainly relied on existing domestic or international analytical work, used relatively basic calculations/data (such as the market value of fisheries, the value of timber sold etc.) and often formed part of a broader analytical effort. Examples of findings in the country reports include prospects for increasing fiscal revenues from natural resources with more than 150 % (Mozambique) and estimates of costs associated with poor environmental management to be equivalent to 3.9 % of GDP (Peru). By involving policy makers in the process of making the country reports, and focusing on environmental and natural resources issues in function of their links with prioritised objectives like economic growth, poverty reduction and public health, the chances to influence policy making have been enhanced. Drawing from the review of these country case studies as well as literature on public policy, this report provides recommendations for governments wishing to undertake an economic analysis of the environment and natural resources management for planning purposes, and for OECD members interested in supporting the process.
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