28 research outputs found
People, context, and devices: Defining the new landscape of TV experiences
Modern technologies (e.g., tablet, smartphone, large public displays) remove many of the constraints that define the scope of what television is or can be, but we often define it based upon our prior TV experiences with broadcast and cable television. This one-day workshop at TVX 2015 will address design challenges and opportunities (e.g., of video streams, social TV apps, second screens) in order to consolidate existing knowledge to describe the changing landscape of TV experiences. It's time to redefine what we think of when we say "television," and this workshop will engage participants in that process
Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?
Tyrosine kinases are important cellular signaling proteins that have a variety of biological activities including cell proliferation and migration. Multiple kinases are involved in angiogenesis, including receptor tyrosine kinases such as the vascular endothelial growth factor receptor. Inhibition of angiogenic tyrosine kinases has been developed as a systemic treatment strategy for cancer. Three anti-angiogenic tyrosine kinase inhibitors (TKIs), sunitinib, sorafenib and pazopanib, with differential binding capacities to angiogenic kinases were recently approved for treatment of patients with advanced cancer (renal cell cancer, gastro-intestinal stromal tumors, and hepatocellular cancer). Many other anti-angiogenic TKIs are being studied in phase I-III clinical trials. In addition to their beneficial anti-tumor activity, clinical resistance and toxicities have also been observed with these agents. In this manuscript, we will give an overview of the design and development of anti-angiogenic TKIs. We describe their molecular structure and classification, their mechanism of action, and their inhibitory activity against specific kinase signaling pathways. In addition, we provide insight into what extent selective targeting of angiogenic kinases by TKIs may contribute to the clinically observed anti-tumor activity, resistance, and toxicity. We feel that it is of crucial importance to increase our understanding of the clinical mechanism of action of anti-angiogenic TKIs in order to further optimize their clinical efficacy
Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis
Injury repair is characterized by the generation of transient cell states important for tissue recovery. Here, the authors present a single cell RNA-seq map of recovery from bleomycin lung injury in mice and uncover a Krt8+ transitional stem cell state that precedes the regeneration of AT1 cells and persists in human lung fibrosis
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Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis.
The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell-cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory programs leading to Krt8+ transitional cells and their terminal differentiation to alveolar type-1 cells. We propose that in lung fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states
Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis.
The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell-cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory programs leading to Krt8+ transitional cells and their terminal differentiation to alveolar type-1 cells. We propose that in lung fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states