| 1. |
- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 2. |
- Schulz, A, et al.
(författare)
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Arctic ozone loss in threshold conditions: Match observations in 1997/1998 and 1998/1999
- 2001
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Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES. - : AMER GEOPHYSICAL UNION. - 0747-7309. ; 106:D7, s. 7495-7503
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Tidskriftsartikel (refereegranskat)abstract
- Chemical ozone loss rates inside the Arctic polar vortex were determined in early 1998 and early 1999 by using the Match technique based on coordinated ozonesonde measurements. These two winters provide the only opportunities in recent years to investigat
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| 3. |
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| 4. |
- Charlton, D. G., et al.
(författare)
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System tests of radiation hard optical links for the ATLAS semiconductor tracker
- 2000
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 443:03-feb, s. 430-446
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Tidskriftsartikel (refereegranskat)abstract
- A prototype optical data and Timing Trigger and Control transmission system based on LEDs and PIN-diodes has been constructed. The system would be suitable in terms of radiation hardness and radiation length for use in the ATLAS SemiConductor Tracker. Bit error rate measurements were performed for the data links and for the links distributing the Timing, Trigger and Control data from the counting room to the front-end modules. The effects of cross-talk between the emitters and receivers were investigated. The advantages of using Vertical Cavity Surface Emitting Lasers (VCSELs) instead of LEDs are discussed.
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| 5. |
- Lee, W. N., et al.
(författare)
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Metabolic sensitivity of pancreatic tumour cell apoptosis to glycogen phosphorylase inhibitor treatment
- 2004
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Ingår i: Br J Cancer. - 0007-0920. ; 91:12, s. 2094-100
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of glycogen breakdown regulate glucose homeostasis by limiting glucose production in diabetes. Here we demonstrate that restrained glycogen breakdown also inhibits cancer cell proliferation and induces apoptosis through limiting glucose oxidation, as well as nucleic acid and de novo fatty acid synthesis. Increasing doses (50-100 microM) of the glycogen phosphorylase inhibitor CP-320626 inhibited [1,2-(13)C(2)]glucose stable isotope substrate re-distribution among glycolysis, pentose and de novo fatty acid synthesis in MIA pancreatic adenocarcinoma cells. Limited oxidative pentose-phosphate synthesis, glucose contribution to acetyl CoA and de novo fatty acid synthesis closely correlated with decreased cell proliferation. The stable isotope-based dynamic metabolic profile of MIA cells indicated a significant dose-dependent decrease in macromolecule synthesis, which was detected at lower drug doses and before the appearance of apoptosis markers. Normal fibroblasts (CRL-1501) did not show morphological or metabolic signs of apoptosis likely due to their slow rate of growth and metabolic activity. This indicates that limiting carbon re-cycling and rapid substrate mobilisation from glycogen may be an effective and selective target site for new drug development in rapidly dividing cancer cells. In conclusion, pancreatic cancer cell growth arrest and death are closely associated with a characteristic decrease in glycogen breakdown and glucose carbon re-distribution towards RNA/DNA and fatty acids during CP-320626 treatment.
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