Echo-Mapping of Swift J1753.5-0127

We present two epochs of coordinated X-ray-optical timing observations of the black hole candidate Swift J1753.5-0127 during its 2005 outburst. The first epoch in July occurred at outburst peak. Two consecutive nights of observations using the McDonald Observatory Argos camera with the Rossi X-ray Timing Explorer show a consistent correlation with an immediate response and an extended tail lasting ~5s. The properties of the variability and the correlation are consistent with thermal reprocessing in an accretion disk. The shortness of the lag suggests a short orbital period consistent with that recently claimed. The second epoch in August used the VLT FORS2 HIT mode again in conjunction with RXTE. Again a repeatable correlation is seen between two independent subsets of the data. In this case, though, the cross-correlation function has an unusual structure comprising a dip followed by a double-peak. We suggest that this may be equivalent to the dip plus single peak structure seen by Kanbach et al. (2001) in XTE J1118+480 and attributed there to synchrotron emission; a similar structure was seen during later activity of Swift J1753.5-0127 by Durant et al. (2008).Comment: 7 pages, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Towards definition of an ECM parts list: An advance on GO categories

Those of us interested in the extracellular matrix (ECM) are faced with significant challenges of definition. ECM proteins are large, complex and assembled into crosslinked insoluble matrices. This has meant that defining the biochemical composition of ECMs has been difficult. Nonetheless, protein chemistry and molecular biology have defined many familiar ECM proteins — collagens, proteoglycans, laminins, thrombospondins, tenascins, fibronectins, etc. With the completion of many genomes it should now be possible to develop complete “parts lists” for the ECM. Such lists are needed for analyzing data from “omic” approaches such as expression arrays, latest-generation sequencing and proteomics. These approaches generate long lists and it is typically necessary to extract from those lists the genes/proteins of interest. Anyone who attempts to do this using the commonly used gene ontology (GO) categories soon discovers that they are largely useless for defining ECM proteins. Many ECM proteins are unannotated and those which are, are sorted, with little evidence of logic or consistency, into diverse categories such “extracellular matrix,” “basement membrane,” “cell surface” and many others. The human and mouse orthologs are often found in different categories and attempts to use GO categories to extract a complete list of ECM genes or proteins from a data set are unsatisfactory at best

Designed to Benefit Whom? An Evaluation of Irish Early Childhood Education and Care Policy using Policy Design Theory.

The overarching aim of the research was to evaluate whether the mechanisms used by the state to implement policy were designed to effectively realise national early childhood education and care (ECEC) policy objectives and children‟s rights within that context. The theoretical framework selected for the project was policy design theory, a framework that emerged from within the field of implementation study. A focus on the distinct implementation phase within the policy process enabled an evaluation of policy achievements relative to policy intentions articulated in various policy documents. Five separate policy tool design models were selected and applied to data which was presented through three distinct research elements. First, a macro-level review of non-financial ECEC policy tools was conducted in order to reveal their scale, scope and nature. This provided the contextual background for the second element which involved a more detailed investigation of the financial policy tools selected and designed by the state. This gradually revealed a complex array of competing rationales informing investment decisions in ECEC in Ireland. Finally, new data were generated through semi-structured interviews and questionnaires to contribute towards a micro-level review in which the social constructions and behavioural assumptions informing ECEC subsidy design in Ireland were explored in more detail. The key findings revealed that policy tools were designed to realise a limited interpretation of policy goals while increasingly perpetuating inequality and promoting stereotypes, thus creating a more socially unjust society. In particular, a focus on the quality of ECEC services was subordinated to a focus on affordability and access and this was even more pronounced amongst supports for social inclusion targets. Likewise, the provision of services and protection of children was the key focus in relation to realising rights for children with inadequate resources being allocated to addressing the participatory element of children‟s rights. An overall lack of co-ordination and biases in investment decisions realised a split system in ECEC where under-threes were cared for while pre-school children were educated. Less visibly, advocates and stakeholders were being managed through the design of policy tools to minimise dissent and conflict thus reducing opportunities for discourse and exploration of the role and ECEC and children‟s rights in Ireland. This thesis argues that it is necessary to encourage a wider and more transparent debate to explore the rationale and values informing the design of ECEC policy tools. Systemic change is also needed to enable and empower advocacy within the sector and improve overall coordination efforts. Finally, burdens and benefits can be more equitably distributed through the redesign of policy tools to provide universal access and the development of a unitary system in which there is space to recognise children as rights holders and citizens

Alternative Splicing of Endothelial Fibronectin Is Induced by Disturbed Hemodynamics and Protects Against Hemorrhage of the Vessel Wall

Objective—Abnormally low-flow conditions, sensed by the arterial endothelium, promote aneurysm rupture. Fibronectin (FN) is among the most abundant extracellular matrix proteins and is strongly upregulated in human aneurysms, suggesting a possible role in disease progression. Altered FN splicing can result in the inclusion of EIIIA and EIIIB exons, generally not expressed in adult tissues. We sought to explore the regulation of FN and its splicing and their possible roles in the vascular response to disturbed flow. Approach and Results—We induced low and reversing flow in mice by partial carotid ligation and assayed FN splicing in an endothelium-enriched intimal preparation. Inclusion of EIIIA and EIIIB was increased as early as 48 hours, with negligible increases in total FN expression. To test the function of EIIIA and EIIIB inclusion, we induced disturbed flow in EIIIAB[superscript −/−] mice unable to include these exons and found that they developed focal lesions with hemorrhage and hypertrophy of the vessel wall. Acute deletion of floxed FN caused similar defects in response to disturbed flow, consistent with a requirement for the upregulation of the spliced isoforms, rather than a developmental defect. Recruited macrophages promote FN splicing because their depletion by clodronate liposomes blocked the increase in endothelial EIIIA and EIIIB inclusion in the carotid model. Conclusions—These results uncover a protective mechanism in the inflamed intima that develops under disturbed flow, by showing that splicing of FN mRNA in the endothelium, induced by macrophages, inhibits hemorrhage of the vessel wall.National Institutes of Health (U.S.) (Grant 5F32HL110484)National Institutes of Health (U.S.) (Grant PO1-HL66105)Howard Hughes Medical InstituteNational Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051

Intravital imaging of metastasis in adult Zebrafish

Background Metastasis is a major clinical problem whose biology is not yet fully understood. This lack of understanding is especially true for the events at the metastatic site, which include arrest, extravasation, and growth into macrometastases. Intravital imaging is a powerful technique that has shown great promise in increasing our understanding of these events. To date, most intravital imaging studies have been performed in mice, which has limited its adoption. Zebrafish are also a common system for the intravital imaging of metastasis. However, as imaging in embryos is technically simpler, relatively few studies have used adult zebrafish to study metastasis and none have followed individual cells at the metastatic site over time. The aim of this study was to demonstrate that adult casper zebrafish offer a convenient model system for performing intravital imaging of the metastatic site over time with single-cell resolution. Methods ZMEL1 zebrafish melanoma cells were injected into 6 to 10-week-old casper fish using an intravenous injection protocol. Because casper fish are transparent even as adults, they could be imaged without surgical intervention. Individual cells were followed over the course of 2 weeks as they arrested, extravasated, and formed macroscopic metastases. Results Our injection method reliably delivered cells into circulation and led to the formation of tumors in multiple organs. Cells in the skin and sub-dermal muscle could be imaged at high resolution over 2 weeks using confocal microscopy. Arrest was visualized and determined to be primarily due to size restriction. Following arrest, extravasation was seen to occur between 1 and 6 days post-injection. Once outside of the vasculature, cells were observed migrating as well as forming protrusions. Conclusions Casper fish are a useful model for studying the events at the metastatic site using intravital imaging. The protocols described in this study are relatively simple. Combined with the reasonably low cost of zebrafish, they offer to increase access to intravital imaging.National Cancer Institute (U.S.) (Grant P30-CA14051)National Institutes of Health (U.S.) (Grant 5-T32-GM007287

The Impact of Policy Tool Selection on Early Childhood Education and Care (ECEC) in Ireland

This paper looks at the range of policy tools selected by the Irish State to fund and develop Early Childhood Education and Care (ECEC). The choice is influenced by cultural norms and ideological predisposition with Ireland demonstrating a pro-market bias and relying on a range of interdependencies and third parties for delivery of services. The tools selected by the Irish State are typically those associated with States that promote a liberal agenda, sometimes referred to as the Anglo/American model (Salamon 2002). However, a closer review of the tools characteristics in Ireland reveal a tendency to adopt a conservative corporatist (Dean 2001) stance that can discourage women’s participation in the workforce

Requirement for the NF-kappa B family member Re1A in the development of secondary lymphoid organs

The transcription factor nuclear factor (NF)-kappaB has been suggested to be a key mediator of the development of lymph nodes and Peyer's patches. However, targeted deletion of NF-kappaB/ Rel family members has not yet corroborated such a function. Here we report that when mice lacking the RelA subunit of NF-kappaB are brought to term by breeding onto a tumor necrosis factor receptor (TNFR)1-deficient background, the trice that are born lack lymph nodes, foyer's patches, and an organized splenic microarchitecture, and have a profound defect in T cell-dependent antigen responses. Analyses of TNFR1/1RelA-deficient embryonic tissues and of radiation chimeras suggest that the dependence on RelA is manifest not in hematopoietic cells but rather in radioresistant stromal cells needed for the development of secondary lymphoid organs

Spatial Microsimulation for Regional Analysis of Marine Related Employment

This paper presents a modelling framework that facilitates marine policy impact assessment at a scale that is below the national level. The spatial microsimulation approach provides a regional level of analysis not generally possible when dealing with ocean economy statistics that are often even difficult to compile at a national level and offers a powerful modelling tool for maritime spatial planning. The spatial microsimulation model is used to profile the spatial distribution of marine related employment in Ireland. It is then used to carry out a micro-level regional assessment of the impact of the Covid-19 pandemic restrictions on the distribution of employment in the Irish ocean economy. The results demonstrate that many of those made unemployed in the ocean economy during the first lock down were outside the main urban centers, particularly in the case of marine tourism and leisure and the marine natural resource based industries. The paper argues that the use of such spatial microsimulation approaches can facilitate a more evidence based policy response to an economic shock, such as the Covid-19 pandemic, in terms of industry and regional specific supports and can also inform more effective marine spatial planning