228 research outputs found

    Working Group 5: Information and training

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    CA-RES report - The Concerted Action to support the implementation of the RES Directive 2009/28/EC (CA-RES

    Working Group 5: Information and training

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    CA-RES report - The Concerted Action to support the implementation of the RES Directive 2009/28/EC (CA-RES

    Germline EMSY sequence alterations in hereditary breast cancer and ovarian cancer families

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    Background: BRCA1 and BRCA2 mutations explain approximately one-fifth of the inherited susceptibility in high-risk Finnish hereditary breast and ovarian cancer (HBOC) families. EMSY is located in the breast cancer-associated chromosomal region 11q13. The EMSY gene encodes a BRCA2-interacting protein that has been implicated in DNA damage repair and genomic instability. We analysed the role of germline EMSY variation in breast/ovarian cancer predisposition. The present study describes the first EMSY screening in patients with high familial risk for this disease.Methods: Index individuals from 71 high-risk, BRCA1/2-negative HBOC families were screened for germline EMSY sequence alterations in protein coding regions and exon-intron boundaries using Sanger sequencing and TaqMan assays. The identified variants were further screened in 36 Finnish HBOC patients and 904 controls. Moreover, one novel intronic deletion was screened in a cohort of 404 breast cancer patients unselected for family history. Haplotype block structure and the association of haplotypes with breast/ovarian cancer were analysed using Haploview. The functionality of the identified variants was predicted using Haploreg, RegulomeDB, Human Splicing Finder, and Pathogenic-or-Not-Pipeline 2.Results: Altogether, 12 germline EMSY variants were observed. Two alterations were located in the coding region, five alterations were intronic, and five alterations were located in the 3'untranslated region (UTR). Variant frequencies did not significantly differ between cases and controls. The novel variant, c.2709 + 122delT, was detected in 1 out of 107 (0.9%) breast cancer patients, and the carrier showed a bilateral form of the disease. The deletion was absent in 897 controls (OR = 25.28; P = 0.1) and in 404 breast cancer patients unselected for family history. No haplotype was identified to increase the risk of breast/ovarian cancer. Functional analyses suggested that variants, particularly in the 3'UTR, were located within regulatory elements. The novel deletion was predicted to affect splicing regulatory elements.Conclusions: These results suggest that the identified EMSY variants are likely neutral at the population level. However, these variants may contribute to breast/ovarian cancer risk in single families. Additional analyses are warranted for rare novel intronic deletions and the 3'UTR variants predicted to have functional roles

    Beyond Text: The co-creation of dramatised character and iStory

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    This article is an outcome of the Beyond Text Project (Autumn 2016-Summer2019)In exploring the impact of reflective and work applied approaches we are curious how vivid new insights and collective ‘Eureka’ momentums occur. These momentums can be forces for work communities to gain competitive advantages. However, we know little of how learning is actively involved in the processing of creating new insights and how such a turning to learning –mode (Pässilä and Owens, 2016) can be facilitated. In the light of cultural studies and art education, we explore how the method of dramatising characters in a specific innovation culture can be facilitated. In this viewpoint we are suggesting one approach for this type of turning to learning which we call Beyond Text, outlining its theoretical underpinnings, its co-creative development & its application In this Beyond Text context we are introducing the method of dramatising characters (DC) and the method of iStory both of which are our own design based on the theory of the four existing categories of research-based theatre (RBT). The findings of this viewpoint article are that both iStory as well as DC methods are useful and practical learning facilitation processes and platforms that can be adopted for use in organizations for promoting reflexivity. Especially they can act as a bridge between various forms of knowing and consummate the other knowledge types (experiential, practical and propositional) in a way that advances practice-based innovation. The originality and value of iStory and DC is that they can be utilized as dialogical evaluation methods when traditional evaluation strategies and pre-determined indicators are unusable

    Effect of alloy treatment and coiling temperature on microstructure and bending performance of ultra-high strength strip steel

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    Two different high strength B-containing microalloyed steel strips produced in industrial processing conditions, one treated with Ti and the other treated with Al, processed by controlled rolling, accelerated cooling and coiling in two different temperatures ranges [723 K to 733 K (450 °C to 460 °C)] and [633 K to 653 K (360 °C to 380 °C)] were subjected to bend testing. The Ti treated steel coiled at the higher temperature 733 K (460 °C) showed the best bending performance. The relatively softer (tensile strength of and even {112} in the sub-surface region as well as uniformity of through thickness texture of the rolled sheet improve the bendability. In the presence of crack initiators, like coarse and brittle TiN particles found in the Ti treated steel, a harder microstructure and the presence of Cube and Goss texture in the sub-surface layer, seen for the lower coiling temperature can cause local transgranular cleavage cracking. Finally the post-uniform elongation obtained from tensile testing and bendability follow a good correlation

    Chemical Linkage to Injected Tissues Is a Distinctive Property of Oxidized Avidin

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    We recently reported that the oxidized avidin, named AvidinOX®, resides for weeks within injected tissues as a consequence of the formation of Schiff's bases between its aldehyde groups and tissue protein amino groups. We also showed, in a mouse pre-clinical model, the usefulness of AvidinOX for the delivery of radiolabeled biotin to inoperable tumors. Taking into account that AvidinOX is the first oxidized glycoprotein known to chemically link to injected tissues, we tested in the mouse a panel of additional oxidized glycoproteins, with the aim of investigating the phenomenon. We produced oxidized ovalbumin and mannosylated streptavidin which share with avidin glycosylation pattern and tetrameric structure, respectively and found that neither of them linked significantly to cells in vitro nor to injected tissues in vivo, despite the presence of functional aldehyde groups. The study, extended to additional oxidized glycoproteins, showed that the in vivo chemical conjugation is a distinctive property of the oxidized avidin. Relevance of the high cationic charge of avidin into the stable linkage of AvidinOX to tissues is demonstrated as the oxidized acetylated avidin lost the property. Plasmon resonance on matrix proteins and cellular impedance analyses showed in vitro that avidin exhibits a peculiar interaction with proteins and cells that allows the formation of highly stable Schiff's bases, after oxidation

    Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

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    <p>Abstract</p> <p>Background</p> <p>Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour.</p> <p>The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient.</p> <p>Methods</p> <p>TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol.</p> <p>Results</p> <p>Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (<it>p </it>= 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72).</p> <p>Conclusion</p> <p>TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.</p
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