Innovations for Sustainability: Pathways to an efficient and post-pandemic future

3rd Report prepared by The World in 2050 initiativ

Trim Regions for Online Computation of From-Region Potentially Visible Sets

International audienceVisibility computation is a key element in computer graphics applications. More specifically, a from-region potentially visible set (PVS) is an established tool in rendering acceleration, but its high computational cost means a from-region PVS is almost always precomputed. Precomputation restricts the use of PVS to static scenes and leads to high storage cost, in particular, if we need fine-grained regions. For dynamic applications, such as streaming content over a variable-bandwidth network, online PVS computation with configurable region size is required. We address this need with trim regions, a new method for generating from-region PVS for arbitrary scenes in real time. Trim regions perform controlled erosion of object silhouettes in image space, implicitly applying the shrinking theorem known from previous work. Our algorithm is the first that applies automatic shrinking to unconstrained 3D scenes, including non-manifold meshes, and does so in real time using an efficient GPU execution model. We demonstrate that our algorithm generates a tight PVS for complex scenes and outperforms previous online methods for from-viewpoint and from-region PVS. It runs at 60 Hz for realistic game scenes consisting of millions of triangles and computes PVS with a tightness matching or surpassing existing approaches

Chimeric Antigen Receptor Library Screening Using a Novel NF-kappa B/NFAT Reporter Cell Platform

Chimeric antigen receptor (CAR)-T cell immunotherapy is under intense preclinical and clinical investigation, and it involves a rapidly increasing portfolio of novel target antigens and CAR designs. We established a platform that enables rapid and high-throughput CAR-screening campaigns with reporter cells derived from the T cell lymphoma line Jurkat. Reporter cells were equipped with nuclear factor kappa B (NF kappa B) and nuclear factor of activated T cells (NFAT) reporter genes that generate a duplex output of enhanced CFP (ECFP) and EGFP, respectively. As a proof of concept, we modified reporter cells with CD19-specific and ROR1-specific CARs, and we detected high-level reporter signals that allowed distinguishing functional from non-functional CAR constructs. The reporter data were highly reproducible, and the time required for completing each testing campaign was substantially shorter with reporter cells (6 days) compared to primary CAR-T cells (21 days). We challenged the reporter platform to a large-scale screening campaign on a ROR1-CAR library, and we showed that reporter cells retrieved a functional CAR variant that was present with a frequency of only 6 in 1.05 x 10(6). The data illustrate the potential to implement this reporter platform into the preclinical development path of novel CAR-T cell products and to inform and accelerate the selection of lead CAR candidates for clinical translation

Follicle-Stimulating Hormone (FSH) Transiently Blocks FSH Receptor Transcription by Increasing Inhibitor of Deoxyribonucleic Acid Binding/Differentiation-2 and Decreasing Upstream Stimulatory Factor Expression in Rat Sertoli Cells

FSH acts through the FSH receptor (FSHR) to modulate cell processes that are required to support developing spermatozoa. Within the testis, only Sertoli cells possess receptors for FSH and are the major targets for this regulator of spermatogenesis. FSH stimulation of Sertoli cells for 24–48 h is known to induce Fshr mRNA expression through an E-box motif (CACGTG) located 25 bp upstream of the transcription start site. In contrast, FSH stimulation for 8 h inhibits Fshr transcription. DNA-protein binding studies performed using nuclear extracts from Sertoli cells show that protein binding to the Fshr promoter E-box was reduced 68% after 6 h of FSH stimulation but increased 191% over basal levels after 48 h of stimulation. The proteins binding to the Fshr E-box were identified as upstream stimulatory factor (USF)-1 and -2. FSH stimulation transiently decreased USF1 levels and increased the expression of the inhibitor of DNA binding/differentiation (ID)-2 repressor protein with the same kinetics as the decreased USF/E-box interactions. Overexpression of ID2 resulted in a dose-dependent decrease in USF-driven Fshr promoter activity in the MSC-1 Sertoli cell line, and ID2 inhibited USF binding to the Fshr E-box. Together, these studies suggest that stimulation of Sertoli cells with FSH transiently decreases expression of the USF1 activator and induces accumulation of the ID2 repressor, to block USF binding to the Fshr promoter and delay activation of Fshr transcription. This FSH-regulated mechanism may explain the cyclical changes in Fshr expression that occurs in Sertoli cells in vivo