Agent-Based Model of Therapeutic Adipose-Derived Stromal Cell Trafficking during Ischemia Predicts Ability To Roll on P-Selectin

Intravenous delivery of human adipose-derived stromal cells (hASCs) is a promising option for the treatment of ischemia. After delivery, hASCs that reside and persist in the injured extravascular space have been shown to aid recovery of tissue perfusion and function, although low rates of incorporation currently limit the safety and efficacy of these therapies. We submit that a better understanding of the trafficking of therapeutic hASCs through the microcirculation is needed to address this and that selective control over their homing (organ- and injury-specific) may be possible by targeting bottlenecks in the homing process. This process, however, is incredibly complex, which merited the use of computational techniques to speed the rate of discovery. We developed a multicell agent-based model (ABM) of hASC trafficking during acute skeletal muscle ischemia, based on over 150 literature-based rules instituted in Netlogo and MatLab software programs. In silico, trafficking phenomena within cell populations emerged as a result of the dynamic interactions between adhesion molecule expression, chemokine secretion, integrin affinity states, hemodynamics and microvascular network architectures. As verification, the model reasonably reproduced key aspects of ischemia and trafficking behavior including increases in wall shear stress, upregulation of key cellular adhesion molecules expressed on injured endothelium, increased secretion of inflammatory chemokines and cytokines, quantified levels of monocyte extravasation in selectin knockouts, and circulating monocyte rolling distances. Successful ABM verification prompted us to conduct a series of systematic knockouts in silico aimed at identifying the most critical parameters mediating hASC trafficking. Simulations predicted the necessity of an unknown selectin-binding molecule to achieve hASC extravasation, in addition to any rolling behavior mediated by hASC surface expression of CD15s, CD34, CD62e, CD62p, or CD65. In vitro experiments confirmed this prediction; a subpopulation of hASCs slowly rolled on immobilized P-selectin at speeds as low as 2 µm/s. Thus, our work led to a fundamentally new understanding of hASC biology, which may have important therapeutic implications

A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum

A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse 1a. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community

Freedom of religion and belief in 21st century Australia: A research report prepared for the Australian Human Rights Commission

In July 2006 the Ministerial Council on Immigration and Multicultural Affairs endorsed the National Action Plan to Build Social Cohesion, Harmony and Security (NAP). Under the NAP, the Australian Human Rights Commission (AHRC) was funded to undertake a range of projects; one is this research report, Freedom of Religion and Belief in the 21st Century. The AHRC commissioned the Australian Multicultural Foundation in association with Monash University and RMIT University to prepare this report. It builds on two previous reports; the first is Article 18: Freedom of Religion and Belief produced in 1998 by the then Human Rights and Equal Opportunity Commission. The second is the 2004 report Religion, Cultural Diversity and Safeguarding Australia, which was produced by the then Department of Immigration and Multicultural and Indigenous Affairs and the Australian Multicultural Foundation, in association with Monash University, RMIT University and the World Conference of Religions for Peace (now Religions for Peace Australia). This research report has responded to the aims of the NAP in 'fostering connections and understanding between Muslims and non-Muslims'. But, considering that other previous and current work has focused specifically on Muslim communities, this research has taken a broader approach. It researched and documents the general issues and concerns of religious and non-religious communities in Australia, principally based on direct consultation with the Australian people. Data from the face-to-face consultations and written submissions provided a valuable perspective on religion in general and religious groups in Australia

Holocene relative sea-level changes in the inner Bredefjord area, southern Greenland

In this paper we present new relative sea-level data from southern Greenland, a key area for understanding the Greenland Ice Sheet (GIS) response to climate change. Within fourteen lakes and marine lagoons from the inner part of Bredefjord (Nordre Sermil