| 1. |
- Andersson, Carl-Henrik, et al.
(author)
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A Genetic Variant of the Sortilin 1 Gene isAssociated with Reduced Risk ofAlzheimer's Disease
- 2016
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 53:4, s. 1353-1363
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder represented by the accumulation of intracellular tau protein and extracellular deposits of amyloid-β (Aβ) in the brain. The gene sortilin 1 (SORT1) has previously been associated with cardiovascular disease in gene association studies. It has also been proposed to be involved in AD pathogenesis through facilitating Aβ clearance by binding apoE/Aβ complexes prior to cellular uptake. However, the neuropathological role of SORT1 in AD is not fully understood. To evaluate the associations between gene variants of SORT1 and risk of AD, we performed genetic analyses in a Swedish case-control cohort. Ten single nucleotide polymorphisms (SNPs), covering the whole SORT1 gene, were selected and genotyped in 620 AD patients and 1107 controls. The SNP rs17646665, located in a non-coding region of the SORT1 gene, remained significantly associated with decreased risk of AD after multiple testing (pc=0.0061). In addition, other SNPs were found to be nominally associated with risk of AD, as well as altered cognitive function and the CSF biomarker Aβ42, but these associations did not survive correction for multiple testing. The fact that SORT1 has been strongly associated with risk of cardiovascular disease is intriguing as cardiovascular disease is also regarded as a risk factor for AD. Finally, increased knowledge about SORT1 function has a potential to increase our understanding of APOE, the strongest risk factor for AD.
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| 2. |
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| 3. |
- Gunnarsson, Anders, 1981, et al.
(author)
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Kinetics of Ligand Binding to Membrane Receptors from Equilibrium Fluctuation Analysis of Single Binding Events
- 2011
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:38, s. 14852-14855
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Journal article (peer-reviewed)abstract
- Equilibrium fluctuation analysis of single binding events has been used to extract binding kinetics of ligand interactions with cell-membrane bound receptors. Time-dependent total internal reflection fluorescence (TIRF) imaging was used to extract residence-time statistics of fluorescently stained liposomes derived directly from cell membranes upon their binding to surface-immobilized antibody fragments. The dissociation rate constants for two pharmaceutical relevant antibodies directed against different B-cell expressed membrane proteins was clearly discriminated, and the affinity of the interaction could be determined by inhibiting the interaction with increasing concentrations of soluble antibodies. The single-molecule sensitivity made the analysis possible without overexpressed membrane proteins, which makes the assay attractive in early drug-screening applications.
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| 4. |
- Gutiérrez Pérez, Cristina, 1972, et al.
(author)
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High frequency of cognitive dysfunction before stroke in the elderly
- 2011
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In: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 26:6, s. 622-629
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Journal article (peer-reviewed)abstract
- Objectives We examined cognitive functions before and in acute phase of stroke studying frequency and profile of cognitive impairment and relationships between cognitive status.MethodsSeventy-four patients with early phase after stroke and 49 healthy controls were included and examined using the Mini-Mental State Examination (MMSE) and a battery of neuropsychological tests. Cognitive status before stroke-onset was investigated using Cognitive Impairment Questionnaire.ResultsCognitive impairments were present in 96% of patients after stroke onset using the battery of neuropsychological tests and in 39% of patients using the MMSE, but in only 9% of controls. Seventy-six percent exhibited reduced executive function and 75% reduced psychomotor tempo. Cognitive dysfunction was present in 52% before stroke onset without any impact on the frequency of impairment in the various cognitive areas in early phase after stroke.ConclusionsCognitive impairment is frequent before the onset of stroke among older people and may partially explain the very high frequency of cognitive impairment observed after stroke onset.
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| 5. |
- Hildeman, Anders, 1984, et al.
(author)
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Level set Cox processes
- 2018
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In: Spatial Statistics. - : Elsevier BV. - 2211-6753. ; 28, s. 169-193
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Journal article (peer-reviewed)abstract
- An extension of the popular log-Gaussian Cox process (LGCP) model for spatial point patterns is proposed for data exhibiting fundamentally different behaviors in different subregions of the spatial domain. The aim of the analyst might be either to identify and classify these regions, to perform kriging, or to derive some properties of the parameters driving the random field in one or several of the subregions. The extension is based on replacing the latent Gaussian random field in the LGCP by a latent spatial mixture model specified using a categorically valued random field. This classification is defined through level set operations on a Gaussian random field and allows for standard stationary covariance structures, such as the Matern family, to be used to model random fields with some degree of general smoothness but also occasional and structured sharp discontinuities. A computationally efficient MCMC method is proposed for Bayesian inference and we show consistency of finite dimensional approximations of the model. Finally, the model is fitted to point pattern data derived from a tropical rainforest on Barro Colorado island, Panama. We show that the proposed model is able to capture behavior for which inference based on the standard LGCP is biased. (C) 2018 Elsevier B.V. All rights reserved.
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| 6. |
- Klasson, Niklas, et al.
(author)
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Valid and efficient manual estimates of intracranial volume from magnetic resonance images
- 2015
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In: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 15
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Journal article (peer-reviewed)abstract
- Background: Manual segmentations of the whole intracranial vault in high-resolution magnetic resonance images are often regarded as very time-consuming. Therefore it is common to only segment a few linearly spaced intracranial areas to estimate the whole volume. The purpose of the present study was to evaluate how the validity of intracranial volume estimates is affected by the chosen interpolation method, orientation of the intracranial areas and the linear spacing between them. Methods: Intracranial volumes were manually segmented on 62 participants from the Gothenburg MCI study using 1.5 T, T-1-weighted magnetic resonance images. Estimates of the intracranial volumes were then derived using subsamples of linearly spaced coronal, sagittal or transversal intracranial areas from the same volumes. The subsamples of intracranial areas were interpolated into volume estimates by three different interpolation methods. The linear spacing between the intracranial areas ranged from 2 to 50 mm and the validity of the estimates was determined by comparison with the entire intracranial volumes. Results: A progressive decrease in intra-class correlation and an increase in percentage error could be seen with increased linear spacing between intracranial areas. With small linear spacing (<= 15 mm), orientation of the intracranial areas and interpolation method had negligible effects on the validity. With larger linear spacing, the best validity was achieved using cubic spline interpolation with either coronal or sagittal intracranial areas. Even at a linear spacing of 50 mm, cubic spline interpolation on either coronal or sagittal intracranial areas had a mean absolute agreement intra-class correlation with the entire intracranial volumes above 0.97. Conclusion: Cubic spline interpolation in combination with linearly spaced sagittal or coronal intracranial areas overall resulted in the most valid and robust estimates of intracranial volume. Using this method, valid ICV estimates could be obtained in less than five minutes per patient.
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| 7. |
- Landgren, Sara, 1980, et al.
(author)
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A novel ARC gene polymorphism is associated with reduced risk of Alzheimer's disease
- 2012
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In: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 119:7, s. 833-842
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid beta (A beta) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute A beta application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3'UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and A beta(1-42). The AA genotype of the newly found 3'-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3'UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed.
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| 8. |
- Palmqvist, Anders, 1966, et al.
(author)
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LOTUS: A co-operation for low temperature urea-based selective catalytic reduction of NOx
- 2004
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In: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191 .- 2688-3627. ; 20014
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Journal article (peer-reviewed)abstract
- The European research co-operation Lotus is presented. The main objectives of the project were i) to show the potential for a urea-based SCR system to comply with the EU standard of years 2005 and 2008 for heavy-duty Diesel engines for different driving conditions with optimal fuel consumption, ii) to reach 95 % conversion of NOx at steady state at full load on a Euro III. engine, iii) to reach 75 % NOx reduction for exhaust temperatures between 200-300°C, and 85 % average NOx reduction between 200-500°C. The energy content of the consumed urea should not exceed 1.0 %, calculated as specific fuel consumption. These targets were met in May 2003 and the Lotus SCR system fulfilled the Euro V NOx legislative objectives for year 2008. Copyright © 2004 SAE International.
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| 9. |
- Simonsson, Lisa, 1982, et al.
(author)
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Continuous Lipid Bilayers Derived from Cell Membranes for Spatial Molecular Manipulation
- 2011
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:35, s. 14027-14032
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Journal article (peer-reviewed)abstract
- Progress with respect to enrichment and separation of native membrane components in complex lipid environments, such as native cell membranes, has so far been very limited. The reason for the slow progress can be related to the lack of efficient means to generate continuous and laterally fluid supported lipid bilayers (SLBs) made from real cell membranes. We show in this work how the edge of a hydrodynamically driven SLB can be used to induce rupture of adsorbed lipid vesicles of compositions that typically prevent spontaneous SLB formation, such as vesicles made of complex lipid compositions, containing high cholesterol content or being derived from real cell membranes. In particular, upon fusion between the moving edge of a preformed SLB and adsorbed vesicles made directly from 3T3 fibroblast cell membranes, the membrane content of the vesicles was shown to be efficiently transferred to the SLB. The molecular transfer was verified using cholera toxin B subunit (CTB) binding to monosialoganglioside receptors (G(M1) and G(M3)), and the preserved lateral mobility was confirmed by spatial manipulation of the G(M1/M3)-CTB complex using a hydrodynamic flow. Two populations of CTB with markedly different drift velocity could be identified, which from dissociation kinetics data were attributed to CTB bound with different numbers of ganglioside anchors.
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| 10. |
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