Control of the adaptive response of the heart to stress via the Notch1 receptor pathway

In the damaged heart, cardiac adaptation relies primarily on cardiomyocyte hypertrophy. The recent discovery of cardiac stem cells in the postnatal heart, however, suggests that these cells could participate in the response to stress via their capacity to regenerate cardiac tissues. Using models of cardiac hypertrophy and failure, we demonstrate that components of the Notch pathway are up-regulated in the hypertrophic heart. The Notch pathway is an evolutionarily conserved cell-to-cell communication system, which is crucial in many developmental processes. Notch also plays key roles in the regenerative capacity of self-renewing organs. In the heart, Notch1 signaling takes place in cardiomyocytes and in mesenchymal cardiac precursors and is activated secondary to stimulated Jagged1 expression on the surface of cardiomyocytes. Using mice lacking Notch1 expression specifically in the heart, we show that the Notch1 pathway controls pathophysiological cardiac remodeling. In the absence of Notch1, cardiac hypertrophy is exacerbated, fibrosis develops, function is altered, and the mortality rate increases. Therefore, in cardiomyocytes, Notch controls maturation, limits the extent of the hypertrophic response, and may thereby contribute to cell survival. In cardiac precursors, Notch prevents cardiogenic differentiation, favors proliferation, and may facilitate the expansion of a transient amplifying cell compartment

Hierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases

Complex hierarchical structure governs emergent properties in biopolymeric materials; yet, the material processing involved remains poorly understood. Here, we investigated the multi-scale structure and composition of the mussel byssus cuticle before, during and after formation to gain insight into the processing of this hard, yet extensible metal cross-linked protein composite. Our findings reveal that the granular substructure crucial to the cuticle’s function as a wear-resistant coating of an extensible polymer fiber is pre-organized in condensed liquid phase secretory vesicles. These are phase-separated into DOPA-rich proto-granules enveloped in a sulfur-rich proto-matrix which fuses during secretion, forming the sub-structure of the cuticle. Metal ions are added subsequently in a site-specific way, with iron contained in the sulfur-rich matrix and vanadium coordinated by DOPA-catechol in the granule. We posit that this hierarchical structure self-organizes via phase separation of specific amphiphilic proteins within secretory vesicles, resulting in a meso-scale structuring that governs cuticle function

Sex-specific development of avian flight performance under experimentally altered rearing conditions

Numerous studies have examined predation risk resulting from the costs of impaired flight performance associated with many key life-history stages such as reproduction and migration. Interestingly, although avian nestlings experience multiple resource-based physiological trade-offs and undergo considerable morphological and physiological changes during postnatal development, there is no data available on how nestlings manage the competing demands of growth and the development of flight ability at this critical life-history stage. We examined numerous morphological traits to determine which are responsible for variation in flight performance in juvenile European starlings (Sturnus vulgaris), a sexually size-dimorphic passerine. We then manipulated maternal quality during chick rearing (via feather clipping) to examine sex-specific sensitivity of fledgling flight performance to the quality of the rearing environment. Results suggest that the mechanics underlying variation in juvenile flight performance are relatively simple, being principally determined by the ratio of pectoral muscle mass to body mass (BM) and the surface area of the wings. Interestingly, although the maternal quality manipulation decreased BM and structural size in daughters, only the flight performance of sons was negatively affected. Our results suggest that a survival-related trait can be significantly affected in the larger sex when raised under stressful conditions. Furthermore, measuring only BM and structural size may not be sufficient in understanding how the sexes are affected by stressful rearing conditions in sexually size-dimorphic species. © The Author 2007. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology. All rights reserved

Hybrid Energy-based Models for Image Generation and Classification

In recent years, deep neural networks (DNNs) have achieved state-of-the-art performance on a wide range of learning tasks. Among those tasks, two fundamental tasks are discriminative models and generative models. However, they are largely separated although prior works have shown that generative training is beneficial to classifiers to alleviate several notorious issues. Energy-based Model (EBM) especially the Joint Energy-based Model(JEM) only needs to train a single network with shared features for discriminative and generative tasks. However, EBMs are expensive to train and very unstable. It is crucial to understand the behavior of EBM training and thus improve the stability, speed, accuracy, and generative quality altogether. This dissertation mainly summarizes my research on EBMs for Hybrid Image Discriminative-Generative Models. We first proposed GMMC which models the joint density p(x, y). As an alternative to the SoftMax classifier utilized in JEM, GMMC has a well-formulated latent feature distribution, which fits well with the generative process of image synthesis. Then we came up with a variety of new training techniques to improve JEM\u27s accuracy, training stability, and speed altogether, and we named it JEM++. Based on JEM++, we analyzed and improved it from three different aspects, 1) the manifold, 2) the data augmentation, 3) the energy landscape. Hence, we propose Manifold-Aware EBM/JEM and Sharpness-Aware JEM to further improve the speed, generation quality, stability, and classification significantly. Beyond MCMC-based EBM, we found we can combine two recent emergent approaches Vision Transformer (ViT) and Denoising Diffusion Probabilistic Model (DDPM) to learn a simple but powerful model for image classification and generation. The new direction can get rid of most disadvantages of EBM, such as the expensive MCMC sampling and instability. Finally, we discuss future research topics including the speed, generation quality, and applications of hybrid models

GREAT3 results I: systematic errors in shear estimation and the impact of real galaxy morphology

We present first results from the third GRavitational lEnsing Accuracy Testing (GREAT3) challenge, the third in a sequence of challenges for testing methods of inferring weak gravitational lensing shear distortions from simulated galaxy images. GREAT3 was divided into experiments to test three specific questions, and included simulated space- and ground-based data with constant or cosmologically-varying shear fields. The simplest (control) experiment included parametric galaxies with a realistic distribution of signal-to-noise, size, and ellipticity, and a complex point spread function (PSF). The other experiments tested the additional impact of realistic galaxy morphology, multiple exposure imaging, and the uncertainty about a spatially-varying PSF; the last two questions will be explored in Paper II. The 24 participating teams competed to estimate lensing shears to within systematic error tolerances for upcoming Stage-IV dark energy surveys, making 1525 submissions overall. GREAT3 saw considerable variety and innovation in the types of methods applied. Several teams now meet or exceed the targets in many of the tests conducted (to within the statistical errors). We conclude that the presence of realistic galaxy morphology in simulations changes shear calibration biases by $\sim 1$ per cent for a wide range of methods. Other effects such as truncation biases due to finite galaxy postage stamps, and the impact of galaxy type as measured by the S\'{e}rsic index, are quantified for the first time. Our results generalize previous studies regarding sensitivities to galaxy size and signal-to-noise, and to PSF properties such as seeing and defocus. Almost all methods' results support the simple model in which additive shear biases depend linearly on PSF ellipticity.Comment: 32 pages + 15 pages of technical appendices; 28 figures; submitted to MNRAS; latest version has minor updates in presentation of 4 figures, no changes in content or conclusion

High Fidelity Simulations of Plume Impingement to the International Space Station

With the retirement of the Space Shuttle, the United States now depends on recently developed commercial spacecraft to supply the International Space Station (ISS) with cargo. These new vehicles supplement ones from international partners including the Russian Progress, the European Autonomous Transfer Vehicle (ATV), and the Japanese H-II Transfer Vehicle (HTV). Furthermore, to carry crew to the ISS and supplement the capability currently provided exclusively by the Russian Soyuz, new designs and a refinement to a cargo vehicle design are in work. Many of these designs include features such as nozzle scarfing or simultaneous firing of multiple thrusters resulting in complex plumes. This results in a wide variety of complex plumes impinging upon the ISS. Therefore, to ensure safe "proximity operations" near the ISS, the need for accurate and efficient high fidelity simulation of plume impingement to the ISS is as high as ever. A capability combining computational fluid dynamics (CFD) and the Direct Simulation Monte Carlo (DSMC) techniques has been developed to properly model the large density variations encountered as the plume expands from the high pressure in the combustion chamber to the near vacuum conditions at the orbiting altitude of the ISS. Details of the computational tools employed by this method, including recent software enhancements and the best practices needed to achieve accurate simulations, are discussed. Several recent examples of the application of this high fidelity capability are presented. These examples highlight many of the real world, complex features of plume impingement that occur when "visiting vehicles" operate in the vicinity of the ISS

Are lizards sensitive to anomalous seasonal temperatures? long-term thermobiological variability in a subtropical species

Alterations in thermal niches have been widely associated with the Anthropocene erosion of reptiles’ diversity. They entail potential physiological constraints for organisms’ perfor- mance, which can lead to activity restrictions and impact fitness and demography. Reptiles are ectotherms which rely on seasonal periodicity to maximize the performance of biological functions. Despite it, the ecological implications of shifts in local temperatures are barely explored at the seasonal scale. This study aims to assess how changes in air temperature and substrate temperature affect the activity, body temperature (Tb) and thermoregulation patterns of the sand lizard, Liolaemus arambarensis (an endangered, microendemic spe- cies from southern Brazil), throughout a four-year period. Field surveys were conducted monthly on a restricted population in a sand-dune habitat. The annual fluctuations of the seasonal temperatures led to significant changes in the activity and Tb of L. arambarensis and shaped thermoregulation trends, suggesting biological plasticity as a key factor in the face of such variability. Lizards tended to maintain seasonal Tb in mild and harsh seasons through increased warming/cooling efforts. Anomalous winter conditions seemed especially critical for individual performance due to their apparent high impact favouring/constraining activity. Activity and thermoregulation were inhibited in frigid winters, probably due to a vul- nerable physiology to intense cold spells determined by higher preferred body temperatures than Tb. Our results warn of a complex sensitivity in lizards to anomalous seasonal tempera- tures, which are potentially enhanced by climate change. The current work highlights the importance of multiannual biomonitoring to disentangle long-term responses in the thermal biology of reptiles and, thereby, to integrate conservation needs in the scope of global change