eBank UK: linking research data, scholarly communication and learning

This paper includes an overview of the changing landscape of scholarly communication and describes outcomes from the innovative eBank UK project, which seeks to build links from e-research through to e-learning. As introduction, the scholarly knowledge cycle is described and the role of digital repositories and aggregator services in linking data-sets from Grid-enabled projects to e-prints through to peer-reviewed articles as resources in portals and Learning Management Systems, are assessed. The development outcomes from the eBank UK project are presented including the distributed information architecture, requirements for common ontologies, data models, metadata schema, open linking technologies, provenance and workflows. Some emerging challenges for the future are presented in conclusion

A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells

PPARγ ligands have been shown to have antiproliferative effects on many cell types. We herein report that a synthetic dominant-negative (DN) PPARγ mutant functions like a growth factor to promote cell cycle progression and cell proliferation in human coronary artery smooth muscle cells (CASMCs). In quiescent CASMCs, adenovirus-expressed DN-PPARγ promoted G1→S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation. DN-PPARγ expression also markedly enhanced positive regulators of the cell cycle, increasing Rb and CDC2 phosphorylation and the expression of cyclin A, B1, D1, and MCM7. Conversely, overexpression of wild-type (WT) or constitutively-active (CA) PPARγ inhibited cell cycle progression and the activity and expression of positive regulators of the cell cycle. DN-PPARγ expression, however, did not up-regulate positive cell cycle regulators in PPARγ-deficient cells, strongly suggesting that DN-PPARγ effects on cell cycle result from blocking the function of endogenous wild-type PPARγ. DN-PPARγ expression enhanced phosphorylation of ERK MAPKs. Furthermore, the ERK specific-inhibitor PD98059 blocked DN-PPARγ-induced phosphorylation of Rb and expression of cyclin A and MCM7. Our data thus suggest that DN-PPARγ promotes cell cycle progression and cell growth in CASMCs by modulating fundamental cell cycle regulatory proteins and MAPK mitogenic signaling pathways in vascular smooth muscle cells (VSMCs)

Projected future climatic forcing on the global distribution of vegetation types

Most emissions scenarios suggest temperature and precipitation regimes will change dramatically across the globe over the next 500 years. These changes will have large impacts on the biosphere, with species forced to migrate to follow their preferred environmental conditions, therefore moving and fragmenting ecosystems. However, most projections of the impacts of climate change only reach 2100, limiting our understanding of the temporal scope of climate impacts, and potentially impeding suitable adaptive action. To address this data gap, we model future climate change every 20 years from 2000 to 2500 CE, under different CO2 emissions scenarios, using a general circulation model. We then apply a biome model to these modelled climate futures, to investigate shifts in climatic forcing on vegetation worldwide, the feasibility of the migration required to enact these modelled vegetation changes, and potential overlap with human land use based on modern-day anthromes. Under a business-as-usual scenario, up to 40% of terrestrial area is expected to be suited to a different biome by 2500. Cold-adapted biomes, particularly boreal forest and dry tundra, are predicted to experience the greatest losses of suitable area. Without mitigation, these changes could have severe consequences both for global biodiversity and the provision of ecosystem services

Intentional research design in implementation science: implications for the use of nomothetic and idiographic assessment

The advancement of implementation science is dependent on identifying assessment strategies that can address implementation and clinical outcome variables in ways that are valid, relevant to stakeholders, and scalable. This paper presents a measurement agenda for implementation science that integrates the previously disparate assessment traditions of idiographic and nomothetic approaches. Although idiographic and nomothetic approaches are both used in implementation science, a review of the literature on this topic suggests that their selection can be indiscriminate, driven by convenience, and not explicitly tied to research study design. As a result, they are not typically combined deliberately or effectively. Thoughtful integration may simultaneously enhance both the rigor and relevance of assessments across multiple levels within health service systems. Background on nomothetic and idiographic assessment is provided as well as their potential to support research in implementation science. Drawing from an existing framework, seven structures (of various sequencing and weighting options) and five functions (Convergence, Complementarity, Expansion, Development, Sampling) for integrating conceptually distinct research methods are articulated as they apply to the deliberate, design-driven integration of nomothetic and idiographic assessment approaches. Specific examples and practical guidance are provided to inform research consistent with this framework. Selection and integration of idiographic and nomothetic assessments for implementation science research designs can be improved. The current paper argues for the deliberate application of a clear framework to improve the rigor and relevance of contemporary assessment strategies

Transformation in a changing climate: a research agenda

The concept of transformation in relation to climate and other global change is increasingly receiving attention. The concept provides important opportunities to help examine how rapid and fundamental change to address contemporary global challenges can be facilitated. This paper contributes to discussions about transformation by providing a social science, arts and humanities perspective to open up discussion and set out a research agenda about what it means to transform and the dimensions, limitations and possibilities for transformation. Key focal areas include: (1) change theories, (2) knowing whether transformation has occurred or is occurring; (3) knowledge production and use; (4), governance; (5) how dimensions of social justice inform transformation; (6) the limits of human nature; (7) the role of the utopian impulse; (8) working with the present to create new futures; and (9) human consciousness. In addition to presenting a set of research questions around these themes the paper highlights that much deeper engagement with complex social processes is required; that there are vast opportunities for social science, humanities and the arts to engage more directly with the climate challenge; that there is a need for a massive upscaling of efforts to understand and shape desired forms of change; and that, in addition to helping answer important questions about how to facilitate change, a key role of the social sciences, humanities and the arts in addressing climate change is to critique current societal patterns and to open up new thinking. Through such critique and by being more explicit about what is meant by transformation, greater opportunities will be provided for opening up a dialogue about change, possible futures and about what it means to re-shape the way in which people live

Narrow optical linewidths in erbium implanted in TiO2_2

Atomic and atom-like defects in the solid-state are widely explored for quantum computers, networks and sensors. Rare earth ions are an attractive class of atomic defects that feature narrow spin and optical transitions that are isolated from the host crystal, allowing incorporation into a wide range of materials. However, the realization of long electronic spin coherence times is hampered by magnetic noise from abundant nuclear spins in the most widely studied host crystals. Here, we demonstrate that Er$^{3+}$ ions can be introduced via ion implantation into TiO$_2$, a host crystal that has not been studied extensively for rare earth ions and has a low natural abundance of nuclear spins. We observe efficient incorporation of the implanted Er$^{3+}$ into the Ti$^{4+}$ site (40% yield), and measure narrow inhomogeneous spin and optical linewidths (20 and 460 MHz, respectively) that are comparable to bulk-doped crystalline hosts for Er$^{3+}$. This work demonstrates that ion implantation is a viable path to studying rare earth ions in new hosts, and is a significant step towards realizing individually addressed rare earth ions with long spin coherence times for quantum technologies

SvAnna: efficient and accurate pathogenicity prediction of coding and regulatory structural variants in long-read genome sequencing.

Structural variants (SVs) are implicated in the etiology of Mendelian diseases but have been systematically underascertained owing to sequencing technology limitations. Long-read sequencing enables comprehensive detection of SVs, but approaches for prioritization of candidate SVs are needed. Structural variant Annotation and analysis (SvAnna) assesses all classes of SVs and their intersection with transcripts and regulatory sequences, relating predicted effects on gene function with clinical phenotype data. SvAnna places 87% of deleterious SVs in the top ten ranks. The interpretable prioritizations offered by SvAnna will facilitate the widespread adoption of long-read sequencing in diagnostic genomics. SvAnna is available at https://github.com/TheJacksonLaboratory/SvAnn a