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© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works Diamond-Blackfan anemia (DBA) is a rare hematopoietic disease characterized by a block in red cell differentiation. Most DBA cases are caused by mutations in ribosomal proteins and characterized by higher than normal activity of the tumor suppressor p53. Higher p53 activity is thought to contribute to DBA phenotypes by inducing apoptosis during red blood cell differentiation. Currently, there are few therapies available for patients with DBA. We performed a chemical screen using zebrafish ribosomal small subunit protein 29 (rps29) mutant embryos that have a p53-dependent anemia and identified calmodulin inhibitors that rescued the phenotype. Our studies demonstrated that calmodulin inhibitors attenuated p53 protein amount and activity. Treatment with calmodulin inhibitors led to decreased p53 translation and accumulation but does not affect p53 stability. A U.S. Food and Drug Administration-approved calmodulin inhibitor, trifluoperazine, rescued hematopoietic phenotypes of DBA models in vivo in zebrafish and mouse models. In addition, trifluoperazine rescued these phenotypes in human CD34+ hematopoietic stem and progenitor cells. Erythroid differentiation was also improved in CD34+ cells isolated from a patient with DBA. This work uncovers a potential avenue of therapeutic development for patients with DBA.

Develop and manage effective real-time streaming solutions by leveraging the power of Microsoft AzureAbout This BookAnalyze your data from various sources using Microsoft Azure Stream AnalyticsDevelop, manage and automate your stream analytics solution with Microsoft AzureA practical guide to real-time event processing and performing analytics on the cloudWho This Book Is ForIf you are looking for a resource that teaches you how to process continuous streams of data in real-time, this book is what you need. A basic understanding of the concepts in analytics is all you need to get started with this bookWhat You Will LearnPerform real-time event processing with Azure Stream AnalysisIncorporate the features of Big Data Lambda architecture pattern in real-time data processingDesign a streaming pipeline for storage and batch analysisImplement data transformation and computation activities over stream of eventsAutomate your streaming pipeline using Powershell and the .NET SDKIntegrate your streaming pipeline with popular Machine Learning and Predictive Analytics modelling algorithmsMonitor and troubleshoot your Azure Streaming jobs effectivelyIn DetailMicrosoft Azure is a very popular cloud computing service used by many organizations around the world. Its latest analytics offering, Stream Analytics, allows you to process and get actionable insights from different kinds of data in real-time.This book is your guide to understanding the basics of how Azure Stream Analytics works, and building your own analytics solution using its capabilities. You will start with understanding what Stream Analytics is, and why it is a popular choice for getting real-time insights from data. Then, you will be introduced to Azure Stream Analytics, and see how you can use the tools and functions in Azure to develop your own Streaming Analytics. Over the course of the book, you will be given comparative analytic guidance on using Azure Streaming with other Microsoft Data Platform resources such