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- Singh, A K, et al.
(författare)
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CFTR and its key role in in vivo resting and luminal acid-induced duodenal HCO3-secretion
- 2008
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 193:4, s. 357-365
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: We investigated the role of the recently discovered, villous-expressed anion exchanger Slc26a6 (PAT1) and the predominantly crypt-expressed cystic fibrosis transmembrane regulator (CFTR) in basal and acid-stimulated murine duodenal HCO3− secretion in vivo, and the influence of blood HCO3− concentration on both.Methods: The proximal duodenum of anaesthetized mice was perfused in situ, and HCO3− secretion was determined by back-titration. Duodenal mucosal permeability was assessed by determining 51Cr-EDTA leakage from blood to lumen.Results: Compared with wild type (WT) littermates basal duodenal HCO3− secretory rates were slightly reduced in Slc26-deficient mice at low (∼21 mm), and markedly reduced at high blood HCO3− concentration (∼29 mm). In contrast, basal HCO3− secretion was markedly reduced in CFTR-deficient mice compared with WT littermates both at high and low blood HCO3− concentration. A short-term application of luminal acid increased duodenal HCO3− secretory rate in Slc26a6-deficient and WT mice to the same degree, but had no stimulatory effect in the absence of CFTR. Luminal acidification to pH 2.5 did not alter duodenal permeability.Conclusions: The involvement of Slc26a6 in basal HCO3− secretion in murine duodenum in vivo is critically dependent on the systemic acid/base status, and this transporter is not involved in acid-stimulated HCO3− secretion. The presence of CFTR is essential for basal and acid-induced HCO3− secretion irrespective of acid/base status. This suggests a coupled action of Slc26a6 with CFTR for murine basal duodenal HCO3− secretion, but not acid-stimulated secretion, in vivo.
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| 3. |
- Abermann, S., et al.
(författare)
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Processing and evaluation of metal gate/high-k/Si capacitors incorporating Al, Ni, TiN, and Mo as metal gate, and ZrO2 and HfO2 as high-k dielectric
- 2007
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 84:5-8, s. 1635-1638
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Tidskriftsartikel (refereegranskat)abstract
- We evaluate various metal gate/high-k/Si capacitors by their resulting electrical characteristics. Therefore, we process MOS gate stacks incorporating aluminium (Al), nickel (Ni), titanium-nitride (TiN), and molybdenum (Mo) as the gate material, and metal organic chemical vapour deposited (MOCVD) ZrO2 and HfO2 as the gate dielectric, respectively. The influence of the processing sequence - especially of the thermal annealing treatment - on the electrical characteristics of the various gate stacks is being investigated. Whereas post metallization annealing in forming gas atmosphere improves capacitance-voltage behaviour (due to reduced interface-, and oxide charge density), current-voltage characteristics degrade due to a higher leakage current after thermal treatment at higher temperatures. The Flatband-voltage values for the TiN-, Mo-, and Ni-capacitors indicate mid-gap pinning of the metal gates, however, Ni seems to be thermally unstable on ZrO2, at least within the process scheme we applied.
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| 7. |
- Lin, Jimmy, et al.
(författare)
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A multidimensional analysis of genes mutated in breast and colorectal cancers
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:9, s. 1304-1318
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Tidskriftsartikel (refereegranskat)abstract
- A recent study of a large number of genes in a panel of breast and colorectal cancers identified somatic mutations in 1149 genes. To identify potential biological processes affected by these genes, we examined their putative roles based on sequence similarity, membership in known functional groups and pathways, and predicted interactions with other proteins. These analyses identified functional groups and pathways that were enriched for mutated genes in both tumor types. Additionally, the results pointed to differences in molecular mechanisms that underlie breast and colorectal cancers, including various intracellular signaling and metabolic pathways. These studies provide a multidimensional framework to guide further research and help identify cellular processes critical for malignant progression and therapeutic intervention.
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| 8. |
- Wood, Laura D, et al.
(författare)
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The genomic landscapes of human breast and colorectal cancers.
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 318:5853, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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