Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

The relative roles of SULF1 and SULF2 enzymes in tumour growth are controversial, but short SULF1/SULF2 splice variants predominate in human mammary tumours despite their non-detectable levels in normal mammary tissue. Compared with the normal, the level of receptor tyrosine kinase (RTK) activity was markedly increased in triple-positive mammary tumours during later stages of tumour progression showing increased p-EGFR, p-FGFR1 and p-cMet activity in triple-positive but not in triple-negative tumours. The abundance of catalytically inactive short SULF1/SULF2 variants permits high levels of HS sulphation and thus growth driving RTK cell signalling in primary mammary tumours. Also observed in this study, however, was increased N-sulphation detected by antibody 10E4 indicating that not only 6-O sulphation but also N-sulphation may contribute to increased RTK cell signalling in mammary tumours. The levels of such increases in not only SULF1/SULF2 but also in pEGFR, pFGFR1, p-cMet and Smad1/5/8 signalling were further enhanced following lymph node metastasis. The over-expression of Sulf1 and Sulf2 variants in mammary tumour-derived MDA-MB231 and MCF7 cell lines by transfection further confirms Sulf1-/Sulf2-mediated differential modulation of growth. The short variants of both Sulf1 and Sulf2 promoted FGF2-induced MDA-MB231 and MCF7 in vitro growth while full-length Sulf1 inhibited growth supporting in vivo mammary tumour cell signalling patterns of growth. Since a number of mammary tumours become drug resistant to hormonal therapy, Sulf1/Sulf2 inhibition could be an alternative therapeutic approach to target such tumours by down-regulating RTK-mediated cell signalling

True Blue

https://digitalcommons.library.umaine.edu/mmb-vp/6583/thumbnail.jp

Interurban Corporate Headquarters Relocation in Canada

This study examines the interurban migration of corporate headquarters in Canada for the period 1970-1982 by investigating the premise that changing socio-economic and political conditions are contributing to the relocation of corporate headquarters. The paper demonstrates that in Canada corporate relocations are tending to create a spatially more concentrated location pattern.Cette étude explore la migration interurbaine des sièges sociaux au Canada à partir de 1970 jusqu'en 1982, en examinant le principe que les conditions changeantes, tant sur les plans socio-économique que politique, contribuent au déplacement des sièges sociaux. Cet article démontre qu'au Canada les migrations des sièges sociaux ont tendance à établir un système spatialement plus concentré

Old Town and Milford Water Power

A brief pamphlet seeking investors to buy land in Milford and Old Town, Maine, so that an public/industrial water power supply system may be constructed for use of those and surrounding towns.https://digicom.bpl.lib.me.us/books_pubs/1286/thumbnail.jp

The roots to conflicting interests among different partners in a dbfm consortium

The paper describes a theory for identifying the roots of conflicting interests in DBFM-consortia. The Theory that ha been developed analyses the possible conflicting interests based on three complementary tension fields, where for every tension field relevant aspects are defined from existing literature. By rating the individual aspects a statement can be made about the possibility that conflicting interests might occur in one of these three tension fields. Because of the fact that (some of) the aspects are controllable (like investments made, or possible future deals), the probability of conflicting interests to occur can be reduced. This should lead to more insight in the way a consortium should be managed with regard to conflicting interests. The principles described are not only applicable to DBFM-projects, but can also be used in other forms of collaboration

Believe me! Why tesla’s recent alleged malfunction further highlights the need for transparent dialogue

On November the 13th, 2022 video footage was released purportedly showing a Tesla Model Y malfunctioning by speeding through the streets of a Chinese city killing two people. Video footage such as this has the potential to undermine trust in AVs. While Tesla has responded by stating they will get to the “truth,” there are questions as to how this truth is to be decided, and perhaps more importantly how the public can trust either Tesla or negative press. We explore the “facts” of the incident and discuss the challenges of building trust in new AVs systems based on transparency. In this article we argue that transparency is more than simply getting to the “truth.” It is fostering a relational dialogue between the facts and stakeholder. Using O’Brien’s window metaphor, this article explores the need for AV manufacturers to consider the content of such incidents, the different perceptions of stakeholders, and the medium through which the content is presented. Apart from the need for independent crash investigators, there is a need for AV manufacturers to go beyond simply’ getting to the truth’ and to engage with the public responsibly

Production Cost Modeling for High Levels of Photovoltaics Penetration

The goal of this report is to evaluate the likely avoided generation, fuels, and emissions resulting from photovoltaics (PV) deployment in several U.S. locations and identify new tools, methods, and analysis to improve understanding of PV impacts at the grid level

What the general dental practitioner needs to know about HPV-related oropharyngeal malignancy.

The rates of oropharyngeal squamous cell carcinoma have continued to rise secondary to the increasing prevalence of the human papillomavirus (HPV). HPV-related disease is typically found in younger patients who do not have the traditional risk factors for malignancy. General dental practitioners (GDPs) often examine patients regularly and may therefore have an opportunity to identify oropharyngeal malignancies at an early stage. However, many GDPs are unfamiliar with oropharyngeal anatomy, pathology and clinical examination. This review summarises the key points in identifying patients with oropharyngeal malignancy who necessitate urgent referral

Beyond ‘witnessing’: children’s experiences of coercive control in domestic violence and abuse

Children’s experiences and voices are underrepresented in academic literature and professional practice around domestic violence and abuse. The project ‘Understanding Agency and Resistance Strategies’ addresses this absence, through direct engagement with children. We present an analysis from interviews with 21 children in the United Kingdom (12 girls and 9 boys, aged 8-18 years), about their experiences of domestic violence and abuse, and their responses to this violence. These interviews were analysed using interpretive interactionism. Three themes from this analysis are presented: a) ‘Children’s experiences of abusive control’, which explores children’s awareness of controlling behaviour by the adult perpetrator, their experience of that control, and its impact on them; b) ‘Constraint’, which explores how children experience the constraint associated with coercive control in situations of domestic violence, and c) ‘Children as agents’ which explores children’s strategies for managing controlling behaviour in their home and in family relationships. The paper argues that, in situations where violence and abuse occurs between adult intimate partners, children are significantly impacted, and can be reasonably described as victims of abusive control. Recognising children as direct victims of domestic violence and abuse would produce significant changes in the way professionals respond to them, by 1) recognising children’s experience of the impact of domestic violence and abuse; 2) recognising children’s agency, undermining the perception of them as passive ‘witnesses’ or ‘collateral damage’ in adult abusive encounters; and 3) strengthening professional responses to them as direct victims, not as passive witnesses to violence