Image Segmentation, Registration, Compression, and Matching

A novel computational framework was developed of a 2D affine invariant matching exploiting a parameter space. Named as affine invariant parameter space (AIPS), the technique can be applied to many image-processing and computer-vision problems, including image registration, template matching, and object tracking from image sequence. The AIPS is formed by the parameters in an affine combination of a set of feature points in the image plane. In cases where the entire image can be assumed to have undergone a single affine transformation, the new AIPS match metric and matching framework becomes very effective (compared with the state-of-the-art methods at the time of this reporting). No knowledge about scaling or any other transformation parameters need to be known a priori to apply the AIPS framework. An automated suite of software tools has been created to provide accurate image segmentation (for data cleaning) and high-quality 2D image and 3D surface registration (for fusing multi-resolution terrain, image, and map data). These tools are capable of supporting existing GIS toolkits already in the marketplace, and will also be usable in a stand-alone fashion. The toolkit applies novel algorithmic approaches for image segmentation, feature extraction, and registration of 2D imagery and 3D surface data, which supports first-pass, batched, fully automatic feature extraction (for segmentation), and registration. A hierarchical and adaptive approach is taken for achieving automatic feature extraction, segmentation, and registration. Surface registration is the process of aligning two (or more) data sets to a common coordinate system, during which the transformation between their different coordinate systems is determined. Also developed here are a novel, volumetric surface modeling and compression technique that provide both quality-guaranteed mesh surface approximations and compaction of the model sizes by efficiently coding the geometry and connectivity/topology components of the generated models. The highly efficient triangular mesh compression compacts the connectivity information at the rate of 1.5-4 bits per vertex (on average for triangle meshes), while reducing the 3D geometry by 40-50 percent. Finally, taking into consideration the characteristics of 3D terrain data, and using the innovative, regularized binary decomposition mesh modeling, a multistage, pattern-drive modeling, and compression technique has been developed to provide an effective framework for compressing digital elevation model (DEM) surfaces, high-resolution aerial imagery, and other types of NASA data

Transcriptional regulation of miR-196b by ETS2 in gastric cancer cells

E26 transformation-specific sequence (ETS)-2 is a transcriptional modulator located on chromosome 21, alterations in its expression have been implicated with a reduced incidence of solid tumors in Down syndrome patients. MicroRNAs (miRNAs) are thought to participate in diverse biological functions; however, the regulation of miRNAs is not well characterized. Recently, we reported that miR-196b is highly expressed in gastric cancers. Herein, we demonstrate that miR-196b expression was significantly repressed by ETS2 during gastric cancer oncogenesis. We demonstrate that knockdown of endogenous ETS2 expression increases miR-196b expression. A genomic region between −751 and −824 bp upstream of the miR-196b transcriptional start site was found to be critical for the repression activity. This putative regulatory promoter region contains three potential ETS2-binding motifs. Mutations within the ETS2 binding sites blocked the repression activity of ETS2. Furthermore, knockdown of ETS2 or overexpression of miR-196b significantly induced migration and invasion in gastric cancer cells. In addition, alterations in ETS2 and miR-196b expression in gastric cancer cell lines affected the expression of epithelial–mesenchymal transition-related genes. The levels of vimentin, matrix metalloproteinase (MMP)-2 and MMP9 were drastically induced, but levels of E-cadherin were decreased in shETS2- or miR-196b-transfected cells. Our data indicate that ETS2 plays a key role in controlling the expression of miR-196b, and miR-196b may mediate the tumor suppressor effects of ETS2. We demonstrated that miR-196b was transcriptionally regulated by ETS2 and there was an inverse expression profile between miR-196b and ETS2 in clinical samples. This finding could be beneficial for the development of effective cancer diagnostic and alternative therapeutic strategies

Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with KrasG12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy

Macrophage biology in development, homeostasis and disease

Macrophages the most plastic cells of the hematopoietic system are found in all tissues and exhibit great functional diversity. They have roles in development, homeostasis, tissue repair, and immunity. While anatomically distinct, resident tissue macrophages exhibit different transcriptional profiles, and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this review, we discuss how macrophages regulate normal physiology and development and provide several examples of their pathophysiologic roles in disease. We define the “hallmarks” of macrophages performing particular functions, taking into account novel insights into the diversity of their lineages, identity, and regulation. This diversity is essential to understand because macrophages have emerged as important therapeutic targets in many important human diseases

Erk1 and Erk2 regulate endothelial cell proliferation and migration during mouse embryonic angiogenesis.

Angiogenesis is a complex process orchestrated by both growth factors and cell adhesion and is initiated by focal degradation of the vascular basement membrane with subsequent migration and proliferation of endothelial cells. The Ras/Raf/MEK/ERK pathway is required for EC function during angiogenesis. Although in vitro studies implicate ERK1 and ERK2 in endothelial cell survival, their precise role in angiogenesis in vivo remains poorly defined. Cre/loxP technology was used to inactivate Erk1 and Erk2 in endothelial cells during murine development, resulting in embryonic lethality due to severely reduced angiogenesis. Deletion of Erk1 and Erk2 in primary endothelial cells resulted in decreased cell proliferation and migration, but not in increased apoptosis. Expression of key cell cycle regulators was diminished in the double knockout cells, and decreased DNA synthesis could be observed in endothelial cells during embryogenesis. Interestingly, both Paxillin and Focal Adhesion Kinase were expressed at lower levels in endothelial cells lacking Erk1 and Erk2 both in vivo and in vitro, leading to defects in the organization of the cytoskeleton and in cell motility. The regulation of Paxillin and Focal Adhesion Kinase expression occurred post-transcriptionally. These results demonstrate that ERK1 and ERK2 coordinate endothelial cell proliferation and migration during angiogenesis