| 1. |
- Lewis, Cathryn M, et al.
(författare)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
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| 2. |
- Garber, Nicholas J, et al.
(författare)
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Distribution and characteristics of crashes at different locations within work zones in Virginia
- 2001
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Ingår i: Proceedings of the Conference Road Safety on Three Continents in Pretoria, South Africa, 20-22 September 2000. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 473-498
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Work zones tend to cause hazardous conditions for vehicle drivers and construction workers since these work zones generate conflicts between construction activities and the traffic, and therefore aggravate the existing traffic conditions. This study investigated the characteristics of work zone crashes in Virginia that occurred between 1996 and 1999. The information on each crash was obtained from the police crash records. Each crash was located in one of five areas of the work zone: 1) advance warning area; 2) transition area; 3) longitudinal buffer area; 4) activity area; and 5) termination area. An analysis of the percentage distributions was then carried out, with respect to the locations of the crashes, the severity, collision types and different types of highways. The proportionality test was used to determine significant differences at the 5% significance level. The results indicate that the Activity Area (Area 4) is the predominant location for work zone crashes regardless of the highway type, and that rear-end crashes are the predominant type of crashes. However, the results also indicated that the proportion of the sideswipe in same direction (SS) crashes in the Transition Area (area 2) is significantly higher than that in the Advance Warning Area (Area 1).
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| 3. |
- Stoka, Veronika, et al.
(författare)
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Lysosomal protease pathways to apoptosis - Cleavage of Bid, not pro-caspases, is the most likely route
- 2001
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 276:5, s. 3149-3157
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the mechanism of lysosome-mediated cell death using purified recombinant pro-apoptotic proteins, and cell-free extracts from the human neuronal progenitor cell line NT2, Potential effectors were either isolated lysosomes or purified lysosomal proteases. Purified lysosomal cathepsins B, H, K, L, S, and X or an extract of mouse lysosomes did not directly activate either recombinant caspase zymogens or caspase zymogens present in an NT2 cytosolic extract to any significant extent. In contrast, a cathepsin L-related protease from the protozoan parasite Trypanosana cruzi, cruzipain, showed a measurable caspase activation rate. This demonstrated that members of the papain family can directly activate caspases but that mammalian lysosomal members of this family may have been negatively selected for caspase activation to prevent inappropriate induction of apoptosis, Given the lack of evidence for a direct role in caspase activation by lysosomal proteases, we hypothesized that an indirect mode of caspase activation may involve the Bcl-2 family member Bid. In support of this, Bid was cleaved in the presence of lysosomal extracts, at a site six residues downstream from that seen for pathways involving capase 8, Incubation of mitochondria with Bid that had been cleaved by lysosomal extracts resulted in cytochrome c release. Thus, cleavage of Bid may represent a mechanism by which proteases that have leaked from the lysosomes can precipitate cytochrome c release and subsequent caspase activation. This is supported by the finding that cytosolic extracts from mice ablated in the bid gene are impaired in the ability to release cytochrome c in response to lysosome extracts, Together these data suggest that Bid represents a sensor that allows cells to initiate apoptosis in response to widespread adventitious proteolysis.
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| 4. |
- Zhao, Ming, et al.
(författare)
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Activation of the p38 MAP kinase pathway is required for foam cell formation from macrophages exposed to oxidized LDL
- 2002
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 110:6, s. 458-468
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Tidskriftsartikel (refereegranskat)abstract
- Endocytosis of oxidized low density lipoproteins (oxLDL) by macrophages, mediated by scavenger receptors, is thought to play a central role in foam cell formation and, thus, in the pathogenesis of atherosclerosis. OxLDL activates several MAP kinases, including the ERK, JNK and p38 MAP kinases, but the role of these activations in oxLDL uptake has not been studied. In the present investigation, we find that SB203580, a specific inhibitor of p38, blocks oxLDL-exposed J774 cells from becoming foam cells. Inhibition of foam cell formation by blockade of the p38 pathway is, at least in part, due to inhibition of oxLDL-induced up-regulation of the scavenger receptor CD36. Using pharmaceutical inhibitors and dominant active MAP kinase kinases, we demonstrated that activation of the p38 pathway, but not the ERK or JNK pathways, is necessary and sufficient to transactivate PPAR?, a nuclear receptor that has recently been shown to play a pivotal role in oxLDL-induced CD36 expression. Our results for the first time demonstrate a regulation of CD36 by p38, and the importance of the p38 pathway in regulation of foam cell formation.
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| 5. |
- Zhou, Qi, et al.
(författare)
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Miscibility, free volume behavior and properties of blends from cellulose acetate and castor oil-based polyurethane
- 2003
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Ingår i: Polymer. - 0032-3861 .- 1873-2291. ; 44:5, s. 1733-1739
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Tidskriftsartikel (refereegranskat)abstract
- A series of blend films from cellulose acetate (CA) and castor oil-based polyurethane (PU) were prepared. Morphology, miscibility, free volume behavior and properties of such blend films were investigated by wide-angle X-ray diffraction (WXRD), infrared, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), positron annihilation lifetime spectroscopy (PALS), thermogravimetric analysis and tensile test. The results indicated that lager free volume cavities did not form at the interface of two polymers although a certain degree of phase separation was found by the studies of SEM and DSC. Strong intermolecular hydrogen bonding interactions at the interface, which was proved by Fourier transform infrared spectroscopy, favors even better molecular packing, that is, PU dispersed in CA continuous phase to form fine microphase separation domain in the CA-rich blends. Due to such special interactions in the fine microphase separation domain structure, optimized properties of tensile strength, breaking elongation and cold-resistivity were obtained in the blend film with 75 wt% CA. The toughness of all the blend films was significantly higher than that of the film CA, owing to the plasticizing of PU elastomer in the blends.
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