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

X-Ray Polarimetry of the Dipping Accreting Neutron Star 4U 1624-49

We present the first X-ray polarimetric study of the dipping accreting neutron star 4U 1624$-$49 with the Imaging X-ray Polarimetry Explorer (IXPE). We report a detection of polarization in the non-dip time intervals with a confidence level of 99.99%. We find an average polarization degree (PD) of $3.1\pm0.7$% and a polarization angle of $81\pm6$ degrees east of north in the 2-8 keV band. We report an upper limit on the PD of 22% during the X-ray dips with 95% confidence. The PD increases with energy, reaching from $3.0\pm0.9$% in the 4-6 keV band to $6\pm2$% in the 6-8 keV band. This indicates the polarization likely arises from Comptonization. The high PD observed is unlikely to be produced by Comptonization in the boundary layer or spreading layer alone. It can be produced by the addition of an extended geometrically thin slab corona covering part of the accretion disk, as assumed in previous models of dippers, and/or a reflection component from the accretion disk

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 20ka, 15ka, 10ka and 5ka, 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 priorit. © 2014 The Authors

Ace Lake: three decades of research on a meromictic, Antarctic lake

Ace Lake (Vestfold Hills, Antarctica) has been investigated since the 1970s. Its close proximity to Davis Station has allowed year-long, as well as summer only, investigations. Ace Lake is a saline meromictic (permanently stratified) lake with strong physical and chemical gradients. The lake is one of the most studied lakes in continental Antarctica. Here we review the current knowledge of the history, the physical and chemical environment, community structure and functional dynamics of the mixolimnion, littoral benthic algal mats, the lower anoxic monimolimnion and the sediment within the monimolimnion. In common with other continental meromictic Antarctic lakes, Ace Lake possesses a truncated food web dominated by prokaryote and eukaryote microorganisms in the upper aerobic mixolimnion, and an anaerobic prokaryote community in the monimolimnion, where methanogenic Archaea, sulphate-reducing and sulphur-oxidizing bacteria occur. These communities are functional in winter at subzero temperatures, when mixotrophy plays an important role in survival in dominant photosynthetic eukaryotic microorganisms in the mixolimnion. The productivity of Ace Lake is comparable to other saline lakes in the Vestfold Hills, but higher than that seen in the more southerly McMurdo Dry Valley lakes. Finally we identify gaps in the current knowledge and avenues that demand further investigation, including comparisons with analogous lakes in the North Polar region

An empirical analysis of the Navy Junior Reserve Officer Training Corps (NJROTC).

http://archive.org/details/empiricalanalysi00zwarNAN

Computer gevoed.

Verslag van een symposium dat georganiseerd werd door de Nederlandse Vereniging van Dietisten en de Nederlandse Vereniging voor Voedingsleer en Levensmiddelentechnologie. De verschillende aspecten van electronische informatie over voeding en de daarbij benodigde soft- en hardware werden belich