Advancing Preclinical Biology for Ewing Sarcoma: An International Effort.

Ewing sarcoma is an aggressive bone and soft-tissue cancer affecting adolescents and young adults. In vitro and in vivo models of Ewing sarcoma have been instrumental in advancing our understanding of Ewing sarcoma biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease for which effective treatment options remain limited. Through an international collaborative effort between the Children’s Oncology Group Bone Tumor Committee and the Euro Ewing Consortium, we review the current landscape of preclinical modeling used in Ewing sarcoma research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and nonmammalian xenografts) model systems. We discuss factors that can influence experimental results, provide testing considerations for both in vitro and in vivo studies, and descriptions of existing preclinical data repositories. We highlight current needs in Ewing sarcoma modeling and the importance of enhanced international cooperative research and patient advocacy efforts which will be critical in expanding our resources of biologically relevant Ewing sarcoma models to enable translation of preclinical findings into effective therapeutic strategies for patients with Ewing sarcoma

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Heat Transfer Through Plasma-Sprayed Thermal Barrier Coatings in Gas Turbines: A Review of Recent Work

A review is presented of how heat transfer takes place in plasma-sprayed (zirconia-based) thermal barrier coatings (TBCs) during operation of gas turbines. These characteristics of TBCs are naturally of central importance to their function. Current state-of-the-art TBCs have relatively high levels of porosity (~15%) and the pore architecture (i.e., its morphology, connectivity, and scale) has a strong influence on the heat flow. Contributions from convective, conductive, and radiative heat transfer are considered, under a range of operating conditions, and the characteristics are illustrated with experimental data and modeling predictions. In fact, convective heat flow within TBCs usually makes a negligible contribution to the overall heat transfer through the coating, although what might be described as convection can be important if there are gross through-thickness defects such as segmentation cracks. Radiative heat transfer, on the other hand, can be significant within TBCs, depending on temperature and radiation scattering lengths, which in turn are sensitive to the grain structure and the pore architecture. Under most conditions of current interest, conductive heat transfer is largely predominant. However, it is not only conduction through solid ceramic that is important. Depending on the pore architecture, conduction through gas in the pores can play a significant role, particularly at the high gas pressures typically acting in gas turbines (although rarely applied in laboratory measurements of conductivity). The durability of the pore structure under service conditions is also of importance, and this review covers some recent work on how the pore architecture, and hence the conductivity, is affected by sintering phenomena. Some information is presented concerning the areas in which research and development work needs to be focussed if improvements in coating performance are to be achieved

Early Formation and Late Merging of the Giant Galaxies

The most luminous galaxies in the present Universe are found at the centers of the most massive dark matter haloes, rich galaxy clusters. In the LCDM cosmology, such massive halo cores are present at redshift z=6 with a comoving number density (as a function of mass interior to ~10 kpc) that is comparable to today's value. The identity of the matter in these central regions is, however, predicted to change as major mergers bring together stars and dark matter from initially well separated sub-units. We use N-body simulations to investigate how these mergers push pre-existing matter outwards in the dominant galaxy while preserving the inner density profile of collisionless matter. It appears that the central regions of large galaxies end up dominated by stars formed in a number of dense cores, well before the last major mergers. The density profile of collisionless matter (stars and dark matter combined) in these central regions appears to be stable and to have attractor-like behavior under merging. This suggests that the baryon loading associated with dissipative contraction and star formation may be erased as subsequent mergers drive the mass distribution back to a universal profile. Such suppression of the effects of baryon loading, along with the early assembly of mass concentrations, may help resolve some apparent challenges to the CDM model for structure formation.Comment: 25 pages, 9 figures, acctepted by ApJ. Minor changes in tex

Strengths and Weaknesses of a Planar Whole-Body Method of (153)Sm Dosimetry for Patients with Metastatic Osteosarcoma and Comparison with Three-Dimensional Dosimetry

PURPOSE: Dosimetric accuracy depends directly upon the accuracy of the activity measurements in tumors and organs. The authors present the methods and results of a retrospective tumor dosimetry analysis in 14 patients with a total of 28 tumors treated with high activities of (153)Sm-ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP) for therapy of metastatic osteosarcoma using planar images and compare the results with three-dimensional dosimetry. MATERIALS AND METHODS: Analysis of phantom data provided a complete set of parameters for dosimetric calculations, including buildup factor, attenuation coefficient, and camera dead-time compensation. The latter was obtained using a previously developed methodology that accounts for the relative motion of the camera and patient during whole-body (WB) imaging. Tumor activity values calculated from the anterior and posterior views of WB planar images of patients treated with (153)Sm-EDTMP for pediatric osteosarcoma were compared with the geometric mean value. The mean activities were integrated over time and tumor-absorbed doses were calculated using the software package OLINDA/EXM. RESULTS: The authors found that it was necessary to employ the dead-time correction algorithm to prevent measured tumor activity half-lives from often exceeding the physical decay half-life of (153)Sm. Measured half-lives so long are unquestionably in error. Tumor-absorbed doses varied between 0.0022 and 0.27 cGy/MBq with an average of 0.065 cGy/MBq; however, a comparison with absorbed dose values derived from a three-dimensional analysis for the same tumors showed no correlation; moreover, the ratio of three-dimensional absorbed dose value to planar absorbed dose value was 2.19. From the anterior and posterior activity comparisons, the order of clinical uncertainty for activity and dose calculations from WB planar images, with the present methodology, is hypothesized to be about 70%. CONCLUSION: The dosimetric results from clinical patient data indicate that absolute planar dosimetry is unreliable and dosimetry using three-dimensional imaging is preferable, particularly for tumors, except perhaps for the most sophisticated planar methods. The relative activity and patient kinetics derived from planar imaging show a greater level of reliability than the dosimetry