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- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 4. |
- Beier, R. A., et al.
(author)
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Borehole resistance and vertical temperature profiles in coaxial borehole heat exchangers
- 2013
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In: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 102, s. 665-675
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Journal article (peer-reviewed)abstract
- Ground source heat pump systems are often coupled to the ground by circulating a fluid through vertical Borehole Heat Exchangers (BHEs). The design of a system requires estimates of the ground thermal conductivity and the borehole thermal resistance, which are usually determined by an in situ thermal response test on a completed borehole. The usual test interpretation methods average the inlet and outlet fluid temperatures and use this mean temperature as the average temperature along the borehole length. This assumption is convenient but does not strictly apply. For a coaxial heat exchanger this paper develops an analytical model for the vertical temperature profiles, which can be used instead of the mean temperature approximation to estimate borehole resistance. The model is verified with measured temperatures on a BHE, where an optical technique allows continuous measurements along a coaxial borehole during a distributed thermal response test. A sensitivity study shows that the proposed method corrects errors in the mean temperature approximation, which overestimates the borehole resistance in a coaxial borehole.
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| 5. |
- Beier, R. A., et al.
(author)
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Vertical temperature profiles and borehole resistance in a U-tube borehole heat exchanger
- 2012
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In: Geothermics. - : Elsevier BV. - 0375-6505 .- 1879-3576. ; 44, s. 23-32
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Journal article (peer-reviewed)abstract
- The design of ground source heat pump systems requires values for the ground thermal conductivity and the borehole thermal resistance. In situ thermal response tests (TRT) are often performed on vertical boreholes to determine these parameters. Most TRT analysis methods apply the mean of the inlet and outlet temperatures of the circulating fluid along the entire borehole length. This assumption is convenient but not rigorous. To provide a more general approach, this paper develops an analytical model of the vertical temperature profile in the borehole during the late-time period of the in situ test. The model also includes the vertical temperature profile of the undisturbed ground. The model is verified with distributed temperature measurements along a vertical borehole using fiber optic cables inside a U-tube for the circulating fluid. The borehole thermal resistance is calculated without the need for the mean temperature approximation. In the studied borehole, the mean temperature approximation overestimates the borehole resistance by more than 20%.
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| 6. |
- Li, Jie, et al.
(author)
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Sphenostylisins A-K : bioactive modified isoflavonoid constituents of the root bark of Sphenostylis marginata ssp. erecta
- 2013
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 78:20, s. 10166-10177
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Journal article (peer-reviewed)abstract
- Sphenostylisins A-C (1-3), three complex dimeric compounds representing two novel carbon skeletons, along with an additional eight new compounds, sphenostylisins D-K (4-11), were isolated from the active chloroform-soluble extract of the root bark of Sphenostylis marginata ssp. erecta using a bioactivity-guided isolation approach. The structures were elucidated by means of detailed spectroscopic analysis, including NMR and HRESIMS analysis, and tandem MS fragmentation was utilized to further support the structures of 1-3. The absolute configuration of sphenostylisin C (3) was established by electronic circular dichroism analysis. Plausible biogenetic relationships between the modified isoflavonoids 1-11 are proposed, and a cyclization reaction of 9 was conducted to support one of the biogenetic proposals made. All of these pure isolates were evaluated against a panel of in vitro bioassays, and among the results obtained, sphenostylisin A (1) was found to be a very potent NF-κB inhibitor (IC50 = 6 nM).
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