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Standardization of sample collection, isolation and analysis methods in extracellular vesicle research
The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the \"ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)\", 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments.
Journal Article
Rebel : my life outside the lines
\"Legendary actor Nick Nolte delivers his most revealing performance yet. This intimate memoir is a tale of art, passion, commitment, addiction, and the quest for personal enlightenment as intense and hypnotic as the man himself. In a career spanning five decades and hundreds of roles, Nick Nolte has become a true Hollywood icon. Rising from a difficult childhood in the rural Midwest to leading roles and a trio of Oscar nominations in the golden West, he has been both celebrated and vilified; survived marriages, divorces, and a string of romances; was named People magazine's 'Sexiest Man Alive'; and suffered public humiliation over his addiction issues, including a drug-fueled trip down the Pacific Coast Highway that resulted in his infamous arrest. Despite these ups and downs, Nolte has remained true to the craft he loves, portraying a diverse range of characters with his trademark physicality and indelible gravelly voice ...\"--Jacket.
Book
Approaching a universal scaling relationship between fracture stiffness and fluid flow
A goal of subsurface geophysical monitoring is the detection and characterization of fracture alterations that affect the hydraulic integrity of a site. Achievement of this goal requires a link between the mechanical and hydraulic properties of a fracture. Here we present a scaling relationship between fluid flow and fracture-specific stiffness that approaches universality. Fracture-specific stiffness is a mechanical property dependent on fracture geometry that can be monitored remotely using seismic techniques. A Monte Carlo numerical approach demonstrates that a scaling relationship exists between flow and stiffness for fractures with strongly correlated aperture distributions, and continues to hold for fractures deformed by applied stress and by chemical erosion as well. This new scaling relationship provides a foundation for simulating changes in fracture behaviour as a function of stress or depth in the Earth and will aid risk assessment of the hydraulic integrity of subsurface sites.
Fractures in rock can be altered geochemically and deformed under stress, affecting fluid flow rates across many orders of magnitude. Here, the authors present a universal scaling relationship between fluid flow and fracture specific stiffness, which will aid the interpretation of subsurface sites.
Journal Article
High-resolution land value maps reveal underestimation of conservation costs in the United States
The justification and targeting of conservation policy rests on reliable measures of public and private benefits from competing land uses. Advances in Earth system observation and modeling permit the mapping of public ecosystem services at unprecedented scales and resolutions, prompting new proposals for land protection policies and priorities. Data on private benefits from land use are not available at similar scales and resolutions, resulting in a data mismatch with unknown consequences. Here I show that private benefits from land can be quantified at large scales and high resolutions, and that doing so can have important implications for conservation policy models. I developed high-resolution estimates of fair market value of private lands in the contiguous United States by training tree-based ensemble models on 6 million land sales. The resulting estimates predict conservation cost with up to 8.5 times greater accuracy than earlier proxies. Studies using coarser cost proxies underestimate conservation costs, especially at the expensive tail of the distribution. This has led to underestimations of policy budgets by factors of up to 37.5 in recent work. More accurate cost accounting will help policy makers acknowledge the full magnitude of contemporary conservation challenges and can help improve the targeting of public ecosystem service investments.
Journal Article
Probing complex geophysical geometries with chattering dust
The modern energy economy and environmental infrastructure rely on the flow of fluids through fractures in rock. Yet this flow cannot be imaged directly because rocks are opaque to most probes. Here we apply chattering dust, or chemically reactive grains of sucrose containing pockets of pressurized carbon dioxide, to study rock fractures. As a dust grain dissolves, the pockets burst and emit acoustic signals that are detected by distributed sets of external ultrasonic sensors that track the dust movement through fracture systems. The dust particles travel through locally varying fracture apertures with varying speeds and provide information about internal fracture geometry, flow paths and bottlenecks. Chattering dust particles have an advantage over chemical sensors because they do not need to be collected, and over passive tracers because the chattering dust delineates the transport path. The current laboratory work has potential to scale up to near-borehole applications in the field.
Chattering dust, or chemically reactive grains of sucrose containing pockets of pressurized carbon dioxide, are used in this experimental approach to study rock fractures. The chattering dust emits acoustic shocks that can be monitored and illuminates fracture geometry.
Journal Article
Galileo unbound : a path across life, the universe and everything
'Galileo Unbound' traces the journey that brought us from Galileo's law of free fall to today's geneticists measuring evolutionary drift, entangled quantum particles moving among many worlds, and our lives as trajectories traversing a health space with thousands of dimensions. Remarkably, common themes persist that predict the evolution of species as readily as the orbits of planets or the collapse of stars into black holes. This book tells the history of spaces of expanding dimension and increasing abstraction and how they continue today to give new insight into the physics of complex systems.-- Publisher's description.
Book
The power of imaging to understand extracellular vesicle biology in vivo
Extracellular vesicles (EVs) are nano-sized lipid bilayer vesicles released by virtually every cell type. EVs have diverse biological activities, ranging from roles in development and homeostasis to cancer progression, which has spurred the development of EVs as disease biomarkers and drug nanovehicles. Owing to the small size of EVs, however, most studies have relied on isolation and biochemical analysis of bulk EVs separated from biofluids. Although informative, these approaches do not capture the dynamics of EV release, biodistribution, and other contributions to pathophysiology. Recent advances in live and high-resolution microscopy techniques, combined with innovative EV labeling strategies and reporter systems, provide new tools to study EVs in vivo in their physiological environment and at the single-vesicle level. Here we critically review the latest advances and challenges in EV imaging, and identify urgent, outstanding questions in our quest to unravel EV biology and therapeutic applications.This Review describes the state of the art in imaging extracellular vesicles in animals to study their release, biodistribution and uptake, and covers labeling strategies, microscopy methods and discoveries made in model organisms.
Journal Article