The philosophy and principles of welding design

The welding designer requires a philosophy for his design responsibilities and a thorough understanding of the basic principles in the subjects covering his responsibilities. The education of the welding designer must provide a spectrum of studies which will define these responsibilities and which will help him to understand and apply the science and technology relevant to his work

Understanding the impacts of exploitation and fragmentation on the upstream migrating, adult river lamprey (Lampetra fluviatilis [L.]): implications for conservation

Globally, freshwater ecosystems are heavily impacted by anthropogenic pressures, including fragmentation and exploitation. Consequently, many negative impacts are observed on numerous fish populations, especially anadromous species.Currently, there is a dearth of knowledge of river lamprey migration in the Humber catchment, one of the UKs largest river lamprey populations and home to the main English lamprey fishery. Consequently, this study aimed to improve our understanding of the impact of fragmentation and exploitation on the upstream spawning migration of river lamprey in the Humber catchment by carrying out fish tracking studies across three consecutive years (2018/19 to 2020/21) in the two main tributaries to the Humber Estuary: Yorkshire Ouse (2018/19 and 2019/20) and Trent (2020/21).Lamprey migration throughout the Humber catchment was severely inhibited by barriers to migration, specifically Naburn and Linton-on-Ouse weirs on the Yorkshire Ouse and Cromwell Weir on the River Trent. These structures significantly impacted lamprey distribution throughout the catchment and reduced the numbers reaching spawning habitat upstream. Despite this, Humber lamprey populations were abundant although the vast majority runs up the Yorkshire Ouse compared to the Trent. Nevertheless, lamprey catches in the Ouse were shown to be more complex than lamprey movements throughout the exploited reach, Naburn Weir passage and vulnerability to capture.Overall, passage remediation is vital to facilitate improved lamprey migration in the Humber catchment, and consequently increase the number of individuals reaching potential spawning habitat whilst management decisions must also account for variability by managing the fishery according to temporal/environmental fluctuations and their potential impact on lamprey behaviour, allowing flexibility in trapping dates and location to ensure sustainability. Nevertheless, the Trent population estimate should be excluded from the current Humber quota with no consumptive take allowed until Cromwell Weir passage is remediated and populations are shown to increase and stabilise relative to the Ouse

Targeting DLL4 in tumors shows preclinical activity but potentially significant toxicity.

Evaluation of: Yan M, Callahan CA, Beyer JC et al.: Chronic DLL4 blockade induces vascular neoplasms. Nature 463, E6-E7 (2010). Delta-like ligand 4 (DLL4) is a Notch ligand that is critical in the formation of a functional vascular network in tumors. Blockade of DLL4-mediated Notch signaling strikingly increases nonproductive angiogenesis, but significantly inhibits tumor growth in preclinical mouse models. Thus, DLL4 has emerged as an attractive target for cancer therapy. Anti-DLL4 antibodies have recently entered clinical trials. However, the potential toxic effects of anti-DLL4 are poorly understood. In this article, Yan et al. reported that chronic DLL4 blockade abnormally activates endothelial cells, causes pathological changes of multiple organs and induces vascular neoplasms. The findings need confirmation in further studies using different tumor-bearing animals but, nevertheless, raise important safety concerns regarding the use of anti-DLL4 agents and warrant monitoring for these effects in clinical trials for targeting DLL4

Towards a competitive and sustainable OA market in Europe - A study of the open access market and policy environment

Deliverable 5.3 of OpenAIRE WP5: FP7 Post Grant Gold Open Access Pilot. This deliverable consists of a study and an annex - and it will be supplemented by a roadmap in May 2017. This study considers the economic factors contributing to the current state of the open-access publishing market, and evaluates the potential for European policymakers to enhance market competition and sustainability in parallel to increasing access. It was commissioned within the scope of the OpenAIRE FP7 Post-Grant Open Access Pilot, and it will be accompanied by a Roadmap document developed with inputs from an expert workshop to be held in The Hague on 20 April 2017. In accordance with the project brief, the study aims to: Explore the current status of the OA publishing market Analyse existing OA publishing business models Evaluate how different national and international policies are complementing each other as a means to achieve a transition to OA Evaluate the impact of the Framework Programme 7 Post-grant OA pilot and its implications for future similar initiatives and the transition to OA. Provide a roadmap leading to a sustainable and competitive market The transition to open access concerns all kinds of academic research outputs, including monographs, journal articles, and data. This study focuses on open access to peer-reviewed research articles, which constitute the bulk of the market and the primary mechanism through which research is disseminated across disciplinary communities and beyond. This report is supplemented by an Annex containing a mid-term evaluation of the FP7 Post-Grant Open Access Pilot.This report will be accompanied by a Roadmap document developed with inputs from an expert workshop to be held in The Hague on 20 April 201

Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases

BACKGROUND: Anti-angiogenic therapy with bevacizumab (an anti-vascular endothelial growth factor (VEGF) antibody) predominantly targets immature blood vessels. Bevacizumab has shown a survival benefit in non-small cell lung carcinoma (NSCLC) and has recently been demonstrated to be safe in patients with brain metastases. However, it is not known whether bevacizumab is effective against brain metastases or whether metastases are representative of their primary in terms of VEGF expression, hypoxia, proliferation and vascular phenotype. The aim of this study was to evaluate these factors in a series of matched primary NSCLCs and brain metastases. METHODS AND RESULTS: Immunohistochemistry showed strong correlation of carbonic anhydrase 9 expression (a marker of hypoxia) in primary and secondary cancers (P=0.0002). However, the proliferation index, VEGF expression, microvessel density and the proportion of mature vessels were discordant between primary and secondary cancers. The mean proportion of mature vessels was 63.2% higher in the brain metastases than the primary tumours (P=0.004). Moreover, the vascular pattern of the primary tumour was not representative of the metastasis. CONCLUSIONS: Brain metastases have a significantly higher proportion of mature vasculature, suggesting that they may be refractory to anti-VEGF therapy. These findings may have implications for clinical trials and biomarker studies evaluating anti-angiogenic agents in brain metastases

Can Modus Vivendi Save Liberalism from Moralism? A Critical Assessment of John Gray’s Political Realism

This chapter assesses John Gray’s modus vivendi-based justification for liberalism. I argue that his approach is preferable to the more orthodox deontological or teleological justificatory strategies, at least because of the way it can deal with the problem of diversity. But then I show how that is not good news for liberalism, for grounding liberal political authority in a modus vivendi undermines liberalism’s aspiration to occupy a privileged normative position vis-à-vis other kinds of regimes. So modus vivendi can save liberalism from moralism, but at cost many liberals will not be prepared to pay