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Integrated Metabolomic and Transcriptomic Analysis of Modified Nucleosides for Biomarker Discovery in Clear Cell Renal Cell Carcinoma
Abstract: Clear cell renal cell carcinoma (ccRCC) accounts for ~75% of kidney cancers. The biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is the truncal driver mutation of most cases of ccRCC. Cancer cells are metabolically reprogrammed and excrete modified nucleosides in larger amounts due to their increased RNA turnover. Modified nucleosides occur in RNAs and cannot be recycled by salvage pathways. Their potential as biomarkers has been demonstrated for breast or pancreatic cancer. To assess their suitability as biomarkers in ccRCC, we used an established murine ccRCC model, harboring Vhl, Trp53 and Rb1 (VPR) knockouts. Cell culture media of this ccRCC model an...
ATR Represents a Therapeutic Vulnerability in Clear Cell Renal Cell Carcinoma
Abstract: Metastatic clear cell renal cell carcinomas (ccRCCs) are resistant to DNA-damaging chemotherapies, limiting therapeutic options for patients whose tumors are resistant to tyrosine kinase inhibitors and/or immune checkpoint therapies. Here we show that mouse and human ccRCCs were frequently characterized by high levels of endogenous DNA damage and that cultured ccRCC cells exhibited intact cellular responses to chemotherapy-induced DNA damage. We identify that pharmacological inhibition of the DNA damage-sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) with the orally administered, potent, and selective drug M4344 (gartisertib) induced antiproliferative effects in...
Entrepreneurship and Culture
The book is an innovative compilation of papers that explore the relationship between cultural features and entrepreneurship. The relative stability of differences in entrepreneurial activity across countries suggests that other than economic factors are at play. The contributions to this edited volume deal with the foundations of entrepreneurship and with the effects of different cultural settings on the incidence and success of entrepreneurs. Topics are individual decision making in a cultural context, regional aspects of entrepreneurship, cross-country differences, and the influence of culture on entrepreneurial activity.
Race and Entrepreneurial Success
A comprehensive analysis of racial disparities and the determinants of entrepreneurial performance—in particular, why Asian-owned businesses on average perform relatively well and why black-owned businesses typically do not. Thirteen million people in the United States—roughly one in ten workers—own a business. And yet rates of business ownership among African Americans are much lower and have been so throughout the twentieth century. In addition, and perhaps more importantly, businesses owned by African Americans tend to have lower sales, fewer employees and smaller payrolls, lower profits, and higher closure rates. In contrast, Asian American-owned businesses tend to be more successf...
The Economics of Self-Employment and Entrepreneurship
As self-employment and entrepreneurship become increasingly important in our modern economies, Simon C. Parker provides a timely, definitive and comprehensive overview of the field. In this book he brings together and assesses the large and disparate literature on these subjects and provides an up-to-date overview of new research findings. Key issues addressed include: the impact of ability, risk, personal characteristics and the macroeconomy on entrepreneurship; issues involved in raising finance for entrepreneurial ventures, with an emphasis on the market failures that can arise as a consequence of asymmetric information; the job creation performance of the self-employed; the growth, innovation and exit behaviour of new ventures and small firms; and the appropriate role for governments interested in promoting self-employment and entrepreneurship. This book will serve as an essential reference guide to researchers, students and teachers of entrepreneurship in economics, business and management and other related disciplines.
Schumpeterian Perspectives on Innovation, Competition and Growth
Recent developments in economics have gone from the recognition of the importance of innovation for growth and the exploration of innovation mechanisms to the incorporation of the results of the previous research into economic models. An important lesson to be drawn from all this research is that a purely macro-based analysis of growth is not enough. The various mechanisms of innovation creation and diffusion, the importance of agent heterogeneity, of market selection processes, of the internal organization of the firm and of organizational routines, and the obsolescence and the consequent emergence of new types of capital goods are a few examples of micro-economic phenomena that contribute decisively to macro-economic development. The papers in this volume approach those issues from a Schumpeterian point of view and tackle issues like the growing importance of knowledge and human capital; increasing returns and path dependence; the role of variety in economic growth; competition and industry evolution.
Handbook of Social Capital and Regional Development
The role of social capital in regional development is a multifaceted topic which is studied all over the world using various methods and across numerous disciplines. It has long been evident that social capital is important for regional development, however, it is less clear how this works in practice. Do all types of social capital have the same effects and are different kinds of regions impacted in the same way? This book is the first to offer an overview of this rapidly expanding field of research and to thoroughly analyse the complex issue of social capital and regional development.
