| 1. |
- Elbaz, Alexis, et al.
(författare)
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Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease
- 2011
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 69:5, s. 778-792
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. Methods: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. Results: Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 30 end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. Interpretation: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects. ANN NEUROL 2011; 69: 778-792
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| 3. |
- Heckman, Michael G., et al.
(författare)
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Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:12, s. 1740-1744
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
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| 4. |
- Ross, Owen A., et al.
(författare)
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Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
- 2011
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Ingår i: Lancet Neurology. - 1474-4465. ; 10:10, s. 898-908
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Tidskriftsartikel (refereegranskat)abstract
- Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
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| 9. |
- Harlin, Ulrika, et al.
(författare)
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Towards efficient automation implementation
- 2006
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Ingår i: IFAC Proc. Vol. (IFAC-PapersOnline). - : IFAC Secretariat. - 9783902661050 ; , s. 71-76
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Konferensbidrag (refereegranskat)abstract
- New technology may contribute to several advantages, but shop-floor requirements need to be considered to achieve expected benefits. Results are based on an industrial study, where new machinery was implemented. Identified critical aspects include transfer of new knowledge related to the modified production system, scenario building, and situation awareness both within and outside the company. These critical aspects may also be relevant during planned changeovers between different levels of automation. An initial model is proposed, describing effects of varying the levels of automation and the potential of automation if critical aspects are sufficiently regarded.
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| 10. |
- Ross, Owen A., et al.
(författare)
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Genomic investigation of alpha-synuclein multiplication and parkinsonism
- 2008
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 63:6, s. 743-750
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Copy number variation is a common polymorphic phenomenon within the human genome. Although the majority of these events are non-deleterious they can also be highly pathogenic. Herein we characterize five families with parkinsonism that have been identified to harbor multiplication of the chromosomal 4q21 locus containing the a-synuclein gene (SNCA). Methods: A methodological approach using fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) 250K SNP microarrays was used to characterize the multiplication in each family and to identify the genes encoded within the region. The telomeric and centromeric breakpoints of each family were further narrowed using semiquantitative polymerase chain reaction with microsatellite markers and then screened for transposable repeat elements. Results: The severity of clinical presentation is correlated with SNCA dosage and does not appear to be overtly affected by the presence of other genes in the multiplicated region. With the exception of the Lister kindred, in each family the multiplication event appears de novo. The type and position of Alu/LINE repeats are also different at each breakpoint. Microsatellite analysis demonstrates two genomic mechanisms are responsible for chromosome 4q21 multiplications, including both SNCA duplication and recombination. Interpretation: SNCA dosage is responsible for parkinsonism, autonomic dysfunction, and dementia observed within each family. We hypothesize dysregulated expression of wild-type (alpha-synuclein results in parkinsonism and may explain the recent association of common SNCA variants in sporadic Parkinson's disease. SNCA genomic duplication results from intraallelic (segmental duplication) or interallelic recombination with unequal crossing over, whereas both mechanisms appear to be required for genomic SNCA triplication.
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| 13. |
- Berglund, M, et al.
(författare)
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VERTICAL INFORMATION TRANSFER IN KNOWLEDGE INTENSE MANUFACTURING
- 2004
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Konferensbidrag (refereegranskat)abstract
- The objective of this paper is to highlight vertical information transfer in relation to operator involvement in development work and to analyze the information channels utilized. A special focus is put on product, production, organisation and information system development. Data were collected in 14 Swedish companies through interviews with operators, production support, and production management. The study indicated a need of strategies for vertical information distribution. Verbal information channels are mostly used. However, formalized information transfer is needed to better utilize the operators’ knowledge and experience for development work as well as to provide personnel with relevant knowledge required for their work. Information flow may be simplified through IT-systems, intranet, documents and instructions, but it implies strong support from management and adapted working methods.
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| 20. |
- Harlin, Ulrika, et al.
(författare)
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INFORMATION AND KNOWLEDGE RELATED TO PRODUCTION REQUIREMENTS DURING CHANGES
- 2005
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Konferensbidrag (refereegranskat)abstract
- Manufacturing systems are increasingly subject to changes. Information and knowledge are therefore essential for the ability to predict potential problems. Results are presented from 16 companies with focus on how production requirements, as perceived from production personnel´s perspective, are considered when changes are planned and realized. A gap between production and information system development is identified according to less competence and authority within the latter area. To improve preparedness, information access in a structured but rapid way, not always dependent on individuals or formalized meetings, is desired. Even though there are advantages with formalized information transfer through e.g. structured work procedures, it is not obvious that user requirements in production are fulfilled. This indicates a need of further research on efficient information system strategies regarding the degree of formal and/or informal information transfer.
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| 21. |
- Harlin, Ulrika, et al.
(författare)
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Towards a Methodology for Assessment of Operator Involvement in Manufacturing Development
- 2002
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Konferensbidrag (refereegranskat)abstract
- Industry is facing global competition and high demands on flexibility, customer adaptation, fast product realization, and rapid industrialization. Consequently, there is a significant pressure on manufacturing systems which requires increasing skill and competence at many levels in the company. This also requires organizations with high involvement of different actors in manufacturing development, why assessment of operator involvement is needed. An issue of growing importance is what strategy Swedish manufacturing industry should develop for the future. In this paper a methodology is presented including an approach for investigating how knowledge-intensive manufacturing can be described, identified and facilitated in 14 Swedish companies. Furthermore, the methodology includes investigation of operator involvement within product, production, organization, and information system development. As this is an ongoing project, the paper presents preliminary results from individual company analyses. However, conceivable results from the proposed approach include characteristics of companies with a great deal of operator involvement in development work, descriptions of implications for operator involvement, the need and use of information as facilitator for development, as well as hindrances and prerequisites for development. Finally, the project can be expected to result in a deeper understanding of how to identify and facilitate development work, in which the manufacturing system operator is well integrated.
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| 22. |
- Hassila, C.J., et al.
(författare)
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Potential of nitrogen atomized alloy 625 in the powder bed fusion laser beam process
- 2022
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 221, s. 110928-110928
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Tidskriftsartikel (refereegranskat)abstract
- Powder based metal additive manufacturing processes like Powder Bed Fusion – Laser Beam utilize gasatomized metal powders as feedstock material. Typically, for nickel-based alloys such as Alloy 625, argongas is used during the atomization process. Considering the larger environmental impact of argon gascompared to nitrogen gas, and the increasing use of gas atomized metal powders, the environmentalimpact of powder based additive manufacturing techniques could be mitigated if gas atomization ofalloys such as Alloy 625 using nitrogen was possible. This work investigates the feasibility of tailoringan alloy to allow atomization using nitrogen gas while remaining within the Alloy 625 specification.This is achieved by limiting the nitrogen pick-up during the atomization process, primarily by reducingthe titanium content. The metallurgical implications of this tailored alloy and the subsequent atomizationusing nitrogen, as well as the attained microstructure from the Powder Bed Fusion – Laser Beam processis investigated and compared to a more common 625 alloy composition which was atomized usingargon. Furthermore, the microstructural development of the alloys after heat treatments are evaluated.Lastly corrosive properties, as well as tensile and impact properties are evaluated both in the as-builtand hot isostatic pressed condition.
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| 24. |
- Liden, R, et al.
(författare)
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Hydrological modelling of fine sediments in the Odzi River, Zimbabwe
- 2001
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Ingår i: WATER SA. - : WATER RESEARCH COMMISSION. - 0378-4738. ; 27:3, s. 303-314
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Tidskriftsartikel (refereegranskat)abstract
- Siltation of reservoirs is a major concern in Zimbabwe. Therefore, development of prediction tools is of great importance. In the present study a recently developed empirical sediment model (MV-SED) based on a daily rainfall-runoff model was applied to st
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