The remodeling of the stromal extracellular matrix (ECM) has a crucial, but incompletely understood role during tumor progression and metastasis. Hic-5, a focal adhesion scaffold protein, has previously been implicated in tumor cell invasion, proliferation and metastasis. To investigate the role of Hic-5 in breast tumor progression in vivo, Hic-5−/− mice were generated and crossed with the Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen mouse. Tumors from the Hic-5−/−;PyMT mice exhibited increased latency and reduced growth, with fewer lung metastases, as compared with Hic-5+/−;PyMT mice. Immunohistochemical analysis showed that Hic-5 is primarily expressed in the cancer-associated fibroblasts (CAFs). Further analysis revealed that the Hic-5−/−;PyMT tumor stroma contains fewer CAFs and exhibits reduced ECM deposition. The remodeling of the stromal matrix by CAFs has been shown to increase tumor rigidity to indirectly regulate FAK Y397 phosphorylation in tumor cells to promote their growth and invasion. Accordingly, the Hic-5−/−;PyMT tumor cells exhibited a reduction in FAK Y397 phosphorylation. Isolated Hic-5−/−;PyMT CAFs were defective in stress fiber organization and exhibited reduced contractility. These cells also failed to efficiently deposit and organize the ECM in two and three dimensions. This, in turn, impacted three-dimensional MDA-MB-231 tumor cell migration behavior. Thus, using a new knockout mouse model, we have identified Hic-5 expression in CAFs as a key requirement for deposition and remodeling of the stromal ECM to promote non-cell autonomous breast tumor progression.

Amato MS, Shaw BR, Olson E, Turyk N, Genskow K, Moore CF. 2016. The challenge of motivated cognition in promoting lake health among shoreline property owners: biased estimation of personal environmental impact. Lake Reserve Manage. 32:386-391.Habitat loss through shoreline development on inland lakes threatens biodiversity. Property owners can reduce their impact by growing vegetated shoreline buffers, but many do not adopt these land management behaviors. One factor that may influence individuals' decisions to participate in conservation initiatives to promote natural shorelines is beliefs about their personal impact. A field study tested whether motivation to protect positive self-view would influence property owners' judgments about their shoreline's impact on lake health. Participants rated photos of their own property and other participants' properties on 4 dimensions: beauty, usability, water quality, and habitat. Linear mixed-effect modeling revealed photos were rated higher by their owners than other participants on all dimensions (mean beta = 1.13, P < 0.05 for all), consistent with the hypothesis that motivation to protect self-view biased property owners to judge their own shoreline development as less harmful than it was judged by others. These results identify a potential barrier to outreach efforts for enlisting property owner cooperation in mitigating habitat degradation from shoreline development.

Proton computed tomography (pCT) is an imaging modality that has been in development to support targeted dose delivery in proton therapy. It aims to accurately map the distribution of relative stopping power. Because protons traverse material media in non-linear paths, pCT requires individual proton processing. Image reconstruction then becomes a time-consuming process. Clinical-use scenarios that require images from billions of protons in less than ten or fifteen minutes have motivated us to use distributed and hardware-accelerated computing methods to achieve fast image reconstruction. Combined use of MPI and GPUs demonstrates that clinically viable image reconstruction is possible. On a 60-node CPU/GPU computer cluster, we achieved efficient strong and weak scaling when reconstructing images from two billion histories in under seven minutes. This represents a significant improvement over the previous state-of-the-art in pCT, which took almost seventy minutes to reconstruct an image from 131 million histories on a single-CPU, single-GPU computer.

Proton computed tomography (pCT) is an imaging modality being developed to support targeted dose delivery in proton therapy. It aims to accurately map the distribution of relative stopping power in the imaged body. Because protons traverse material in non-linear paths, pCT requires individual proton processing and image reconstruction becomes a time-consuming process. We discuss the transformation of image reconstruction techniques from single CPU/GPU implementations to create a hybrid multi-CPU/GPU approach. We demonstrate a reduction of computation time from almost 7 hours down to 53 seconds.

The top supercomputers typically have aggregate memories in excess of 100 TB, with simulations running on these systems producing datasets of comparable size. The size of these datasets and the speed with which they are produced define the minimum performance that modern analysis and visualization must achieve. We report on interactive visualizations of large simulations performed on Kraken at the National Institute for Computational Sciences using the parallel cosmology code Enzo, with grid sizes ranging from 10243 to 64003. In addition to the asynchronous rendering of over 570 timesteps of a 40963 simulation (150 TB in total), we developed the ability to stream the rendering result to multi-panel display walls, with full interactive control of the renderer(s).

This simulation uses a flux-limited diffusion solver to explore the radiation hydrodynamics of early galaxies, in particular, the ionizing radiation created by Population III stars. At the time of this rendering, the simulation has evolved to a redshift of 3.5. The simulation volume is 11.2 comoving megaparsecs, and has a uniform grid of 10243 cells, with over 1 billion dark matter and star particles. This animation shows a combined view of the baryon density, dark matter density, radiation energy and emissivity from this simulation. The multi-variate rendering is particularly useful because is shows both the baryonic matter ("normal") and dark matter, and the pressure and temperature variables are properties of only the baryonic matter. Visible in the gas density are "bubbles", or shells, created by the radiation feedback from young stars. Seeing the bubbles from feedback provides confirmation of the physics model implemented. Features such as these are difficult to identify algorithmically, but easily found when viewing the visualization

Simulations running on the top supercomputers are routinely producing multi-terabyte data sets. Enabling scientists, at their home institutions, to analyze, visualize and interact with these data sets as they are produced is imperative to the scientific discovery process. We report on interactive visualizations of large simulations performed on Kraken at the National Institute for Computational Sciences using the parallel cosmology code Enzo, with grid sizes ranging from 10243 to 64003. In addition to the asynchronous rendering of over 570 timesteps of a 40963 simulation (150 TB in total), we developed the ability to stream the rendering result to multipanel display walls, with full interactive control of the renderer(s).

The Synchrotron Radiation Center (SRC) is dedicated to enabling of innovative research using IR, ultraviolet, and soft X-ray synchrotron radiation. It delivers beam time with high reliability (99%) and continues to improve the Aladdin storage ring complex. A lower emittance tuning has been commissioned to support a microfocus capability. SRC successfully installed an APPLE II undulator providing elliptically polarized light with lattice compensation for flexible scanning. Installation of a new IR beamline at SRC is providing synchrotron chemical imaging with unprecedented structural and chemical information, simultaneously. In addition, SRC has established a strong education and outreach program to bring the knowledge and power of light source science to a wider national community. It is moving forward into the future by developing a new micro focus beamline producing a diffraction-limited focus of about 500nm at 22eV, proposing an additional diffraction-limited chemical imaging beamline, and advancing the Wisconsin Free Electron Laser (WiFEL) concept.

Increasingly massive datasets produced by simulations beg the question How will we connect this data to the computational and display resources that support visualization and analysis? This question is driving research into new approaches to allocating computational, storage, and network resources. In this paper we explore potential solutions that couple system resources in new ways. Examples of what we mean by resource-coupled computations abound. For example, remote visualization is an activity that may couple data and large computation resources at the shared facility to client software and display hardware at the remote site. In situ analysis and visualization contemporaneously merges simulation and analysis onto the shared resource of the supercomputing platform. Co-analysis approaches seek to directly couple simulations running on a primary supercomputer to live analysis running on an optimized visualization and analysis platform over a high-performance network. Consequently, we are working on a systems approach to modeling the end-to-end activity of extracting understanding from computational models. In this paper we present our methods and results from experiments.

Many prototype projects aspire to develop a sustainable model of immersive radiological volume visualization for virtual anatomic education. Some have focused on distributed or parallel architectures. However, very few, if any others, have combined multi-location, multi-directional, multi-stream sharing of video, audio, desktop applications, and parallel stereo volume rendering, to converge on an open, globally scalable, and inexpensive collaborative architecture and implementation method for anatomic teaching using radiological volumes. We have focused our efforts on bringing this all together for several years. We outline here the technology we're making available to the open source community and a system implementation suggestion for how to create global immersive virtual anatomy classrooms. With the releases of Access Grid 3.1 and our parallel stereo volume rendering code, inexpensive globally scalable technology is available to enable collaborative volume visualization upon an award-winning framework. Based upon these technologies, immersive virtual anatomy classrooms that share educational or clinical principles can be constructed with the setup described with moderate technological expertise and global scalability.

Rural communities in amenity rich areas continue to struggle in their efforts to manage growth and development in ways that protect key natural resources. Recent developments in GIS have made the development of alternative policy scenarios relatively easy to document and analyze. Parallel advances in landscape ecology have produced new metrics for estimating different dimensions of landscape fragmentation. Bringing these developments together, I compare the potential consequences of a set of proposed regulation schemes to evaluate likely impacts on landscape fragmentation. Researchers at the University of Wisconsin – Stevens Point created a spatial record of historic parcel and land use maps that allowed us to estimate baseline trends against which policy alternatives could be compared. I then projected future development based on a policy proposal presently being discussed as part of a comprehensive planning effort in the study area. The analysis shows a mixed ability of landscape metrics to more meaningfully express the outcomes of land use alternatives. I conclude by discussing the likelihood of policy adoption based on the potential consequences for actual landowners in the area.

For more than a decade, various approaches have been taken to teach anatomy using immersive virtual reality. This is the first complete anatomy course we are aware of which directly substitutes immersive virtual reality via stereo volume visualization of clinical radiological datasets for cadaver dissection. The students valued highly the new approach and the overall course was very well received. Students performed well on examinations. The course efficiently added human anatomy to the University of Chicago undergraduate biology electives.

Reelin and Disabled 1 (Dab1) are essential for positioning migrating neurons in the developing neocortex. Cell-autonomous RNA interference-mediated suppression of Dab1 in migrating neurons destined for layer 2/3 shifted the median position of these cells to deeper positions within the cortex. At the time of migration arrest [embryonic day 20 (E20) to E21], Dab1-suppressed cells were underrepresented in the upper ∼40 μm of the cortex compared with controls, suggesting that Dab1 is essential for somal translocation through the cell-dense cortical plate. Closer examination of the morphology of Dab1-suppressed neurons at E20 revealed simplified leading processes that are less likely to contact the marginal zone (MZ), in which high levels of Reelin are expressed. Examination of Dab1-suppressed cells 3 d later (postnatal day 2) revealed simplified dendrites that are also less likely to contact the MZ. These data reveal a cell-autonomous role of Dab1 in dendritogenesis in the neocortex and suggest that remodeling of the leading process of a migrating neuron into a nascent dendrite by Reelin/Dab1 signaling plays an important role in cell positioning.