Global Projects Scott, W. Richard; Levitt, Raymond E; Orr, Ryan J
06/2011
eBook
As the world's population continues to grow, there is an ever increasing need for huge investment in basic infrastructure: water and sewage, energy production and distribution, transportation and ...telecommunication. At the same time, infrastructure systems in developed countries are deteriorating and in need of renewal. Today, many of the engineering and economic problems surrounding infrastructure construction projects have been solved, but the threat of social misalignments and political conflicts renders the development and management of such projects more challenging than ever before. This book presents a new theoretical framework that allows us to analyze the institutional and social movement processes, both negative and positive, that surround global infrastructure projects as they confront cross-national and cross-sectoral (such as private-public partnerships) institutional differences. The value of this framework is illustrated through a series of studies on a wide range of infrastructure projects, including roads, railroads, ports, airports, water supply and energy pipelines.
More so than other types of social actors, the professions in modern society have assumed leading roles in the creation and tending of institutions. They are the preeminent institutional agents of ...our time. Different professions work in various ways: some attempt to create general cultural-cognitive frameworks; others to devise normative prescriptions to guide behavior; and still others to exercise coercive authority. Also, individual professionals assume varying roles within their professional community: some concentrate on devising and testing general principles, others transport these ideas to varying communities; and still others work to apply the principles to individual cases. Professions themselves adhere to an institutional model, but this model has undergone important changes over time.
I summarize seven general trends in the institutional analysis of organizations which I view as constructive and provide evidence of progress in the development of this perspective. I emphasize ...corrections in early theoretical limitations as well as improvements in the use of empirical indicators and an expansion of the types of organizations included and issues addressed by institutional theorists.
Cancers are highly heterogeneous and contain many passenger and driver mutations. To functionally identify tumor suppressor genes relevant to human cancer, we compiled pools of short hairpin RNAs ...(shRNAs) targeting the mouse orthologs of genes recurrently deleted in a series of human hepatocellular carcinomas and tested their ability to promote tumorigenesis in a mosaic mouse model. In contrast to randomly selected shRNA pools, many deletion-specific pools accelerated hepatocarcinogenesis in mice. Through further analysis, we identified and validated 13 tumor suppressor genes, 12 of which had not been linked to cancer before. One gene,
XPO4, encodes a nuclear export protein whose substrate, EIF5A2, is amplified in human tumors, is required for proliferation of XPO4-deficient tumor cells, and promotes hepatocellular carcinoma in mice. Our results establish the feasibility of in vivo RNAi screens and illustrate how combining cancer genomics, RNA interference, and mosaic mouse models can facilitate the functional annotation of the cancer genome.
This paper presents a review and critique of the 20-year-old literature on institutional distance, which has greatly proliferated. We start with a discussion of the three institutional perspectives ...that have served as a theoretical foundation for this construct: organizational institutionalism, institutional economics, and comparative institutionalism. We use this as an organizing framework to describe the different ways in which institutional distance has been conceptualized and measured, and to analyze the most common organizational outcomes that have been linked to institutional distance, as well as the proposed explanatory mechanisms of those effects. We substantiate our qualitative review with a meta-analysis, which synthesizes the main findings in this area of research. Building on our review and previous critical work, we note key ambiguities in the institutional distance literature related to underlying theoretical perspectives and associated mechanisms, distance versus profile effects, and measurement. We conclude with actionable recommendations for improving institutional distance research.
Monitoring the progress of DNA molecules through a membrane pore has been postulated as a method for sequencing DNA for several decades. Recently, a nanopore-based sequencing instrument, the Oxford ...Nanopore MinION, has become available, and we used this for sequencing the Saccharomyces cerevisiae genome. To make use of these data, we developed a novel open-source hybrid error correction algorithm Nanocorr specifically for Oxford Nanopore reads, because existing packages were incapable of assembling the long read lengths (5-50 kbp) at such high error rates (between ∼5% and 40% error). With this new method, we were able to perform a hybrid error correction of the nanopore reads using complementary MiSeq data and produce a de novo assembly that is highly contiguous and accurate: The contig N50 length is more than ten times greater than an Illumina-only assembly (678 kb versus 59.9 kbp) and has >99.88% consensus identity when compared to the reference. Furthermore, the assembly with the long nanopore reads presents a much more complete representation of the features of the genome and correctly assembles gene cassettes, rRNAs, transposable elements, and other genomic features that were almost entirely absent in the Illumina-only assembly.
New infection treatments are urgently needed to combat the rising threat of multi-drug resistant bacteria. Despite early clinical set-backs attention has re-focused on host defense proteins (HDPs), ...as potential sources for new and effective antimicrobial treatments. HDPs appear to act at multiple targets and their repertoire includes disruptive membrane and intracellular activities against numerous types of pathogens as well as immune modulatory functions in the host. Importantly, these novel activities are associated with a low potential for emergence of resistance and little crossresistance with other antimicrobial agents. Based on these properties, HDPs appear to be ideal candidates for new antibiotics; however, their development has been plagued by the many therapeutic limitations associated with natural peptidic agents. This review focuses on HDP mimetic approaches aimed to improve metabolic stability, pharmacokinetics, safety and manufacturing processes. Early efforts with β-peptide or peptoid analogs focused on recreating stable facially amphiphilic structures but demonstrated that antimicrobial activity was modulated by more, complex structural properties. Several approaches have used lipidation to increase the hydrophobicity and membrane activity. One lead compound, LTX-109, has entered clinical study as a topical agent to treat impetigo and nasal decolonization. In a more significant departure from the amino acid like peptidomimetics, considerable effort has been directed at developing amphiphilic compounds that recapitulate the structural and biological properties of HDPs on small abiotic scaffolds. The lead compound from this approach, brilacidin, has completed two phase 2 studies as an intravenous agent for skin infections.
Antimicrobial peptides (AMPs) provide protection against a variety of pathogenic bacteria and are, therefore, an important part of the innate immune system. Over the past decade, there has been ...considerable interest in developing AMPs as intravenously administered antibiotics. However, despite extensive efforts in the pharmaceutical and biotechnology industry, it has proven difficult to achieve this goal. While researchers have solved some relatively simple problems such as susceptibility to proteolysis, more severe problems have included the expense of the materials, toxicity, poor efficacy, and limited tissue distribution. In this Account, we describe our efforts to design and synthesize “foldamers”-- short sequence-specific oligomers based on arylamide and β-amino acid backbones, which fold into well-defined secondary structures-- that could act as antimicrobial agents. We reasoned that small “foldamers” would be less expensive to produce than peptides, and might have better tissue distribution. It should be easier to fine-tune the structures and activities of these molecules to minimize toxicity. Because the activities of many AMPs depends primarily on their overall physicochemical properties rather than the fine details of their precise amino acid sequences, we have designed and synthesized very small “coarse-grained” molecules, which are far simpler than naturally produced AMPs. The molecular design of these foldamers epitomizes the positively charged amphiphilic structures believed to be responsible for the activity of AMPs. The designed oligomers show greater activity than the parent peptides. They have also provided leads for novel small molecule therapeutics that show excellent potency in animal models for multidrug resistant bacterial infections. In addition, such molecules can serve as relatively simple experimental systems for investigations aimed at understanding the mechanism of action for this class of antimicrobial agents. The foldamers’ specificity for bacterial membranes relative to mammalian membranes appears to arise from differences in membrane composition and physical properties between these cell types. Furthermore, because experimental coarse-graining provided such outstanding results, we developed computational coarse-grained models to enable molecular dynamic simulations of these molecules with phospholipid membranes. These simulations allow investigation of larger systems for longer times than conventional molecular dynamics simulations, allowing us to investigate how physiologically relevant surface concentrations of AMP mimics affect the bilayer structure and properties. Finally, we apply the principles discovered through this work to the design of inexpensive antimicrobial polymers and materials.
Although the fields of organization theory and social movement theory have long been viewed as belonging to different worlds, recent events have intervened, reminding us that organizations are ...becoming more movement-like - more volatile and politicized - while movements are more likely to borrow strategies from organizations. Organization theory and social movement theory are two of the most vibrant areas within the social sciences. This collection of original essays and studies both calls for a closer connection between these fields and demonstrates the value of this interchange. Three introductory, programmatic essays by leading scholars in the two fields are followed by eight empirical studies that directly illustrate the benefits of this type of cross-pollination. The studies variously examine the processes by which movements become organized and the role of movement processes within and among organizations. The topics covered range from globalization and transnational social movement organizations to community recycling programs.
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly ...1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15541. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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