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- Junttila, T T, et al.
(författare)
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Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells
- 2005
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Ingår i: Cancer Research. - 1538-7445. ; 65:4, s. 1384-1393
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Tidskriftsartikel (refereegranskat)abstract
- ErbB1 and ErbB2 receptors are well-characterized targets for anticancer drugs, but the clinical relevance of the related ErbB4 receptor is unknown. Here, we have assessed the clinical significance of the proteolytically cleavable ErbB4 isoforms in breast cancer patients and investigated their functions in vitro. The expression of transcripts encoding the cleavable ErbB4 isoforms associated with estrogen receptor-{alpha} (ER) expression (P < 0.001) and a high histologic grade of differentiation (P ≤ 0.002) in real-time reverse transcription-PCR analysis of 62 breast cancer samples. Despite high ErbB4 mRNA expression levels in a subset of samples, ErbB4 gene amplification was not observed. High ErbB4 protein expression levels, as assessed by immunohistochemistry, associated with a favorable outcome in ER-positive cases from a series of 458 breast cancer patients (P = 0.01), whereas no association between ErbB4 expression and survival was found among women with ER-negative cancer (P = 0.86). However, nuclear ErbB4 immunoreactivity was associated with poor survival as compared with women whose cancer had membranous ErbB4 staining (P = 0.04). In vitro, overexpression of a cleavable ErbB4 isoform in ER-positive breast cancer cells resulted in translocation of a proteolytically released intracellular ErbB4 receptor fragment into the nucleus, as well as, enhanced proliferation, anchorage-independent growth, and estrogen response element–mediated transcriptional activity. These results suggest that the association of ErbB4 expression with clinical outcome is dependent on the subcellular localization of ErbB4 and that a proteinase-cleavable ErbB4 isoform promotes growth of ER-positive breast cancer and enhances ER-mediated gene transcription.
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- Klein, Richard J.T., et al.
(författare)
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Portfolio screening to support the mainstreaming of adaptation to climate change into development assistance
- 2007
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Ingår i: Climate change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 84:1, s. 23-44
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Tidskriftsartikel (refereegranskat)abstract
- The need to mainstream adaptation to climate change into development planning and ongoing sectoral decision-making is increasingly recognised, and several bilateral and multilateral development agencies are starting to take an interest. Over the past years at least six development agencies have screened their project portfolios, generally with two goals in mind: (1) to ascertain the extent to which existing development projects already consider climate risks or address vulnerability to climate variability and change, and (2) to identify opportunities for incorporating climate change explicitly into future projects. As each portfolio screening was conducted independently, the broader lessons emerging from the screenings have not been systematically analysed. In this paper we assess the screening activities to date, focusing on both the results and the methods applied. Based on this assessment we identify opportunities for development agencies to expand their current focus on the links between climate and development. Most agencies already consider climate change as a real but uncertain threat to future development, but they have given less thought to how different development patterns might affect vulnerability to climate change. The screenings undertaken have shown the need to take a comprehensive approach to adaptation and its integration into development planning and sectoral decision-making, and a number of policy initiatives have been taken to promote such integration. We provide some initial guidance as to how portfolio screening can be carried out in a way that would allow agencies to assess systematically the relevance of climate change to their ongoing and planned development projects.
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- Ahlquist, Mårten, et al.
(författare)
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An experimental and theoretical study of the mechanism of stannylcupration of alpha, beta-acetylenic ketones and esters
- 2006
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 12:10, s. 2866-2873
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Tidskriftsartikel (refereegranskat)abstract
- The title reaction has been investigated by experimental and computational (DFT) techniques, and subsequently compared to the corresponding carbocupration reaction, with particular emphasis oil the stereoselectivity. For stannylcupration of an ynone substrate, only the anti-addition product is observed, whereas for the corresponding ynoate substrate, the stereoselectivity can be affected by the reaction conditions: in the presence of methanol as proton donor, the initial syn-addition product can be trapped, whereas a syn/anti mixture is obtained in a non-protic solvent. This is in sharp contrast to the carbocupration of the same ynone substrate with a cyanocuprate (RCu(CN)Li), which is highly selective for syn-addition. The product selectivities can be understood from a detailed computational characterization of the reaction paths, and in particular from the relative stabilities of the vinyl cuprate and allenolate intermediates. It is suggested that the stereodetermining step is protonation of vinyl cuprate intermediates.
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- Eastwood, D. S., et al.
(författare)
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X-ray scattering from two-dimensionally patterned magnetic thin film nanoscale arrays
- 2007
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Ingår i: Superlattices and Microstructures. - : Elsevier BV. - 0749-6036 .- 1096-3677. ; 41:2-3, s. 163-167
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Tidskriftsartikel (refereegranskat)abstract
- Thin metallic films patterned into nanoscale periodic arrays give rise to coherent satellites on either side of the specular reflection when illuminated at grazing incidence with x-rays. We have used grazing incidence x-ray scattering to probe the crystallography of two-dimensional patterned arrays. Excellent agreement is obtained between experimental scattering profiles and those simulated using a fast Fourier transform method. The technique is appropriate to any shape of patterned element. It is shown that the symmetry of the satellites in an azimuthal rotation map of the scattered intensity provides a sensitive means of measuring symmetry of the two-dimensional order in patterned nanostructures. Furthermore, the in-plane coherence length of the array is found to determine the lineshape of the coherent satellite peaks. We find very good agreement between experimental and simulated rotation maps for the two dimensional array.
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- Tanner, Anne C R, et al.
(författare)
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Clinical characteristics and microbiota of progressing slight chronic periodontitis in adults.
- 2007
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Ingår i: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 34:11, s. 917-930
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Tidskriftsartikel (refereegranskat)abstract
- AIM: This study sought clinical and microbial risk indicators for progressing slight periodontitis. MATERIAL AND METHODS: One hundred and seventeen periodontally healthy or slight periodontitis adults (20-40 years) were monitored clinically at 6-month intervals followed by supragingival cleaning. Inter-proximal sites with >1.5 mm increase in clinical attachment over 18 months were considered disease active. Subgingival plaque was analysed by 78 16S rDNA and 38 whole-genomic DNA probes and by PCR to Porphyromonas gingivalis and Tannerella forsythia. Characteristics were compared between active and inactive subjects. RESULTS: Twenty-two subjects showed disease activity principally at molars. Mean baseline gingival and plaque indices, bleeding on probing, probing depth and clinical attachment level (CAL) were higher in active subjects. DNA probes detected species and not-yet-cultivated phylotypes from chronic periodontitis, although few species were associated with active subjects. By PCR P. gingivalis (p=0.007) and T. forsythia (p=0.075) were detected more frequently during monitoring in active subjects. Stepwise logistic analysis associated baseline levels of gingival index, clinical attachment and bleeding with subsequent clinical attachment loss. CONCLUSIONS: Gingivitis and CAL were significantly associated with progressing slight periodontitis in 20--40-year-old adults. Species associated with moderate and advanced chronic periodontitis were detected in slight periodontitis.
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| 18. |
- Tanner, Anne C R, et al.
(författare)
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Subgingival and tongue microbiota during early periodontitis.
- 2006
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Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 85:4, s. 318-323
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal infections have a microbial etiology. Association of species with early disease would be useful in determining which microbes initiate periodontitis. We hypothesized that the microbiota of subgingival and tongue samples would differ between early periodontitis and health. A cross-sectional evaluation of 141 healthy and early periodontitis adults was performed with the use of oligonucleotide probes and PCR. Most species differed in associations with sample sites; most subgingival species were associated with subgingival samples. Few species were detected more frequently in early periodontitis by DNA probes. Porphyromonas gingivalis and Tannerella forsythia (Tannerella forsythensis) were associated with early periodontitis by direct PCR. In conclusion, the microbiota of tongue samples was less sensitive than that of subgingival samples in detecting periodontal species, and there was overlap in species detected in health and early periodontitis. Detection of periodontal pathogens in early periodontitis suggests an etiology similar to that of more advanced disease.
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