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- Barocchi, M A, et al.
(författare)
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A pneumococcal pilus influences virulence and host inflammatory responses
- 2006
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:8, s. 2857-2862
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.
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| 4. |
- Kim, M.-Y., et al.
(författare)
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Respondent burden and patient-perceived validity of the PDQ-39
- 2006
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 113:2, s. 132-137
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the respondent burden and patient-perceived content validity of the Parkinson's disease (PD)-specific health status questionnaire PDQ-39, and the linguistic validity of its revised Swedish version.MATERIALS AND METHODS: Eighteen PD patients completed the revised Swedish version of the PDQ-39. Respondent burden was assessed by recording the time taken to complete the questionnaire. Content and linguistic validity was evaluated qualitatively.RESULTS: Patients with mild, moderate and advanced PD needed a mean time of 9.5, 11.3 and 20.1 min, respectively, to complete the PDQ-39. One-third of the patients identified irrelevant items and 50% identified important health-related areas that were missing. Revisions had eliminated previous linguistic problems with the Swedish PDQ-39.CONCLUSIONS: Undue respondent burden challenged the appropriateness of the PDQ-39 among patients with more advanced disease. Overall content validity was acceptable but compromised by lack of important content areas. Observations supported the linguistic validity of the revised Swedish PDQ-39.
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| 5. |
- 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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| 7. |
- Bunta, Juraj, et al.
(författare)
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Solvating, manipulating, damaging, and repairing DNA in a computer
- 2007
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Ingår i: International Journal of Quantum Chemistry. - New York : Wiley. - 0020-7608 .- 1097-461X. ; 107:2, s. 279-291
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Tidskriftsartikel (refereegranskat)abstract
- This work highlights four different topics in modeling of DNA: (i) the importance of water and ions together with the structure and function of DNA; the hydration structure around the ions appears to be the determining factor in the ion coordination to DNA, as demonstrated in the results of our MD simulations; (ii) how MD simulations can be used to simulate single molecule manipulation experiments as a complement to reveal the structural dynamics of the studied biomolecules; (iii) how damaged DNA can be studied in computer simulations; and (iv) how repair of damaged DNA can be studied theoretically.
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| 8. |
- Curescu, Calin, 1975-, et al.
(författare)
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Utility-based Adaptive Resource Allocation in Hybrid Wireless Networks
- 2005
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Ingår i: The 2nd IEEE International Conference on Quality of Service in Heterogeneous Wired/Wireless Networks QSHINE,2005. - Conference Proceedings : IEEE Computer Society. ; , s. 44-
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Konferensbidrag (refereegranskat)abstract
- Service availability in wireless networks is highly dependent on efficient resource allocation and guaranteed Quality of Service (QoS) amid overloads and failures. This paper addresses optimal bandwidth allocation in a hybrid network (cellular and ad hoc), where added reach through an ad hoc overlay is combined with the stability and essential services of a cellular network. The paper builds on a near optimal approach in which Resource-Utility functions are used as a means of adaptive delivery of QoS, user differentiation, and maximisation of system level utility. It distinguishes between non-adaptive, semi-adaptive, and fully adaptive applications. First, the global cellular bandwidth allocation (in the presence of multiple routes through ad hoc relays) is cast in terms of a Linear Programming problem. Second, a heuristic algorithm that has far lower computational overhead and accrues at worse 12% less than the utility of the optimal solution is presented. Both algorithms are implemented within a model of a hybrid network on top of the Jsim simulation environment. Comparative tudies are made to show effective load balancing and crash tolerance in the presence of a high traffic overload.
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