| 1. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 2. |
- Djoussé, Luc, et al.
(författare)
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Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
- 2004
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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| 3. |
- Harland, N.R., et al.
(författare)
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Adaptive-passive control of vibration transmission in beams using electro/magnetorheological fluid filled inserts
- 2001
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Ingår i: IEEE Transactions on Control Systems Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 1063-6536 .- 1558-0865. ; 9:2, s. 209-220
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Tidskriftsartikel (refereegranskat)abstract
- A method for the control of the transmission of bending vibrations in beams is described. A composite beam (a structural insert) is inserted into a part of the structure to affect the transmission there. The insert comprises two elastic face plates and a central core of tunable fluid such as an electrorheological (ER) or magnetorheological (MR) fluid. By adjusting the applied electric or magnetic field the rheological properties of the fluid can be controlled and hence so too can the vibration transmission properties of the insert. Theoretical results concerning the transmission of vibrations in beam-like structures are reviewed. Numerical results are presented for the transmission through ER and MR fluid filled inserts, with experimental results for an ER case. The transmission is seen to show a pass/stopband structure with the stopbands being tunable.
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| 4. |
- Harland, N.R., et al.
(författare)
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Auto-tuning of a tunable structural insert
- 2001
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Ingår i: Proceedings of ISMA 25, 2000 International Conference on Noise and Vibration Engineering. - Leuven : Katholieke universiteit. - 9073802725 ; , s. 99-106
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Konferensbidrag (refereegranskat)abstract
- This paper considers the auto-tuning of structural inserts, placed into part of a structure to affect the transmission of bending vibrations there. Auto-tuning has the potential to optimise the vibration reduction produced by the insert even in the face of time-varying changes in the dynamic properties of the structure or of the disturbance signal. A particular type of tunable insert is considered, namely one which comprises two elastic face plates and a central core of tunable fluid such as an electro-rheological (ER) or magneto-rheological (MR) fluid. By adjusting the applied electric or magnetic field the visco-elastic properties of the fluid can be controlled and hence so, too, can the vibration transmission properties of the insert. The autotuning scheme itself utilises a downstream sensor, which provides a measure of the vibration energy after the insert, and an adaptive algorithm in the feedback loop. The adaptive algorithm determines the optimal field applied to the tunable insert.
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| 5. |
- Jones, Dylan T, et al.
(författare)
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Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis.
- 2003
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 101:8, s. 3174-80
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Tidskriftsartikel (refereegranskat)abstract
- Activation of the phosphatidylinositol 3- kinase/AKT pathway antagonizes apoptosis in diverse cellular systems. We previously showed that human plasma activated AKT and potently blocked the ability of chlorambucil or gamma radiation to induce apoptosis of B-chronic lymphocytic leukemia (CLL) cells. Here we report experiments that identify albumin as the major component of plasma that blocks CLL cell killing by chlorambucil or radiation. Intact plasma depleted of albumin by chromatography on Cibacron blue-Sepharose or plasma from a subject with analbuminemia failed either to activate AKT or to protect CLL cells from chlorambucil-induced apoptosis. Both functions were restored by re-addition of albumin. The protective action of albumin as well as AKT activation was compromised by the binding of lipids. Fluorescence-activated cell sorter (FACScan) analysis demonstrated the uptake of fluoresceinated albumin by CLL cells. Accumulation of albumin in intracellular vesicles was also shown by confocal microscopy. Indirect inhibition of AKT activation by the phosphatidylinositol 3-kinase inhibitor LY294002 reversed the blockade of chlorambucil-induced killing by plasma albumin. The data suggest that activation of AKT consequent to binding of albumin by CLL cells blocks chlorambucil- and radiation-induced apoptosis. Strategies designed to block albumin-induced antiapoptotic signaling may, therefore, be of value in enhancing cytotoxic drug action on CLL cells.
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| 6. |
- Jones, Kristine, et al.
(författare)
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Cost-effectiveness of critical time intervention to reduce homelessness among persons with mental illness
- 2003
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Ingår i: Psychiatric Services. - : American Psychiatric Association Publishing. - 1075-2730 .- 1557-9700. ; 54:6, s. 884-890
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cost-effective programs are needed to assist homeless persons with severe mental illness in their transition from shelters to community living. The authors investigated the cost-effectiveness of the critical time intervention program, a time-limited adaptation of intensive case management, which has been shown to significantly reduce recurrent homelessness among men with severe mental illness. Methods: Ninety-six study participants recruited from a psychiatric program in a men's public shelter from 1991 to 1993 were randomly assigned to the critical time intervention program or to usual services. Costs and housing outcomes for the two groups were examined over 18 months. Results: Over the study period, the critical time intervention group and the usual services group incurred mean costs of $52,374 and $51,649, respectively, for acute care services, outpatient services, housing and shelter services, criminal justice services, and transfer income. During the same period, the critical time intervention group experienced significantly fewer homeless nights than the usual care group (32 nights versus 90 nights). For each willingness-to-pay value - the additional price society is willing to spend for an additional nonhomeless night - greater than $152, the critical time intervention group exhibited a significantly greater net housing stability benefit, indieating cost-effectiveness, compared with usual care. Conclusions: Although difficult to conduct, studies of the cost-effectiveness of community mental health programs can yield rich information for policy makers and program planners. The critical time intervention program is not only an effective method to reduce recurrent homelessness among persons with severe mental illness but also represents a cost-effective alternative to the status quo.
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| 7. |
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| 8. |
- Jones, Richard W., et al.
(författare)
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A framework for intelligent medical diagnosis using the theory of evidence
- 2002
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Ingår i: Knowledge-Based Systems. - 0950-7051 .- 1872-7409. ; 15:1-2, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- In designing fuzzy logic systems for fault diagnosis, problems can be encountered in the choice of symptoms to use fuzzy operators and an inability to convey the reliability of the diagnosis using just one degree of membership for the conclusion. By turning to an evidential framework, these problems can be resolved whilst still preserving a fuzzy relational model structure. The theory of evidence allows for utilisation of all available information. Relationships between sources of evidence determine appropriate combination rules. By generating belief and plausibility measures it also communicates the reliability of the diagnosis, and completeness of information. In this contribution medical diagnosis is considered using the theory of evidence, in particular the diagnosis of inadequate analgesia is considered
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| 9. |
- Jones, Richard W., et al.
(författare)
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Computerised anaesthesia monitoring using fuzzy trend templates
- 2001
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Ingår i: Artificial Intelligence in Medicine. - 0933-3657 .- 1873-2860. ; 21:1-3, s. 247-251
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Tidskriftsartikel (refereegranskat)abstract
- The task of administering anaesthesia requires the clinician to be vigilant for long periods of time to detect the onset of adverse conditions. Large amounts of data must be analysed in real-time and, if a problem is detected, it must be diagnosed as a matter of urgency, this being done while other management protocols are being carried out. For these reasons it would be of benefit if automated decision support could be provided for anaesthesia monitoring, to lighten the cognitive load on the anaesthetist. The Sentinel anaesthesia monitor has been developed with this objective in mind. It uses a fuzzy time-domain pattern matching technique, termed fuzzy trend templates, to detect vaguely specified patterns in multiple physiological data streams. These patterns are representative of symptoms associated with undesirable patient states. The system is capable of detecting trends and states such as 'significant rise' and 'high', and associating vague duration and temporal intervals with individual trends. Fuzzy trend templates have proven to be quite intuitive to specify, given linguistic (anaesthetists') knowledge about the problem domain. Sentinel's implementation of fuzzy trend templates also uses an extension to fuzzy logic based on the theory of evidence, to handle situations where desired information is not available, for example, when sensors are not being used. In off-line testing, Sentinel has achieved sensitivity and specificity of above 90% in the diagnosis of seven common or serious conditions that can arise during anaesthesia
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| 10. |
- Li, Jian-Liang, et al.
(författare)
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A genome scan for modifiers of age at onset in Huntington disease : The HD MAPS study.
- 2003
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:3, s. 682-7
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
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