Bringing together the recent and relevant contributions of over 125 scientists from industry, government, and academia in North America and Western Europe, Alternative Toxicological Methods explores the development and validation of replacement, reduction, and refinement alternatives (the 3Rs) to animal testing. Internationally recognized scientist

The end of the 20th century brought with it a revolution in molecular biology that culminated in advances such as the completion of the human genome. This has brought optimism to the fields of toxicology and environmental health, and the anticipation that molecular biomarkers might soon come of age and have a major impact on human and environmental

Comprehensive Biomaterials II, Second Edition, Seven Volume Set brings together the myriad facets of biomaterials into one expertly-written series of edited volumes. Articles address the current status of nearly all biomaterials in the field, their strengths and weaknesses, their future prospects, appropriate analytical methods and testing, device applications and performance, emerging candidate materials as competitors and disruptive technologies, research and development, regulatory management, commercial aspects, and applications, including medical applications. Detailed coverage is given to both new and emerging areas and the latest research in more traditional areas of the field. Particular attention is given to those areas in which major recent developments have taken place. This new edition, with 75% new or updated articles, will provide biomedical scientists in industry, government, academia, and research organizations with an accurate perspective on the field in a manner that is both accessible and thorough. Reviews the current status of nearly all biomaterials in the field by analyzing their strengths and weaknesses, performance, and future prospects Covers all significant emerging technologies in areas such as 3D printing of tissues, organs and scaffolds, cell encapsulation; multimodal delivery, cancer/vaccine - biomaterial applications, neural interface understanding, materials used for in situ imaging, and infection prevention and treatment Effectively describes the many modern aspects of biomaterials from basic science, to clinical applications

Imaging with high spatial resolution and high specificity within intact tissues at depth has long been a critical research objective for implementation in biological studies. The development of imaging tools with the capability of deep imaging at cellular resolution would allow for more realistic and complicated biological hypotheses to be tested in their natural environment - intravitally. The most challenging aspects of such tool developments involve light scattering and aberration, which cause the light to distort along its propagation direction, limiting both its imaging depth and resolution. This thesis attempts to provide several solutions to overcomes these challenges. To overcome light scattering, imaging within the short-wave infrared region (SWIR, wavelength 1 - 2.5 micrometers) is explored in chapters 2-4. In chapter 2 and 3, reflectance confocal and fluorescence confocal microscopy are demonstrated providing 2-4 times deeper penetration than any previously reported work and preclude the possibility of using one-photon confocal microscopy for deep imaging, a method that has been rarely discussed. Furthermore, a study on the impact of staining inhomogeneity on the depth limit of fluorescence confocal microscopy also demonstrated the potential of confocal microscopy combined with SWIR and low staining inhomogeneity to achieve unprecedented imaging depth. After demonstrating the deep imaging capability of one-photon imaging at depth with a SWIR light source, a multimodal system combining three-photon, third-harmonic, and optical coherence microscopy (OCM) is demonstrated in chapter 4. This multimodal system was able to achieve simultaneous imaging depth comparable to imaging with multiple contrast mechanisms in terms of the fluorescence, the harmonic signal, and the backscattering. Furthermore, this multimodal system provided complementary information about the mouse in vivo and represented a powerful intravital biological imaging tool. To overcome light aberration, adaptive optical methods are demonstrated in chapters 5-7. In chapter 5, a sensorless, adaptive optics, and indirect wavefront sensing system is demonstrated to improve SWIR-excited three-photon imaging, achieving about 7x signal enhancement in the mouse hippocampus area. This method is based on using the nonlinear three-photon fluorescence signal as feedback and involves light exposure during the optimization process. To reduce light exposure, a more direct wavefront sensing method is explored using a SWIR OCM system to directly sense the complex field of a biological sample in chapter 6. The advantage of this system, including its potential high-speed wavefront sensing and offline wavefront estimation, and its limitations with respect to phase stability are discussed. Finally, in chapter 7, a direct wavefront sensing method based on a cheap silicon wavefront sensor is presented. This method provides a convenient approach for aberration measurement with any experiment that involves SWIR ultrafast laser. This thesis shows the great promise to achieve high-resolution deep tissue imaging at a larger depth by combining longer wavelength at short-wave infrared region and adaptive optics. It is anticipated that this thesis work will open doors to much more exciting biological research in the near future.

This book describes developments in the field of super-resolution fluorescence microscopy or nanoscopy. In 11 chapters, distinguished scientists and leaders in their respective fields describe different nanoscopy approaches, various labeling technologies, and concrete applications. The topics covered include the principles and applications of the most popular nanoscopy techniques STED and (f)PALM/STORM, along with advances brought about by fluorescent proteins and organic dyes optimized for fluorescence nanoscopy. Furthermore, the photophysics of fluorescent labels is addressed, specifically for improving their photoswitching capabilities. Important applications are also discussed, such as the tracking and counting of molecules to determine acting forces in cells, and quantitative cellular imaging, respectively, as well as the mapping of chemical reaction centers at the nano-scale. The 2014 Chemistry Nobel Prize® was awarded for the ground-breaking developments of super-resolved fluorescence microscopy. In this book, which was co-edited by one of the prize winners, readers will find the most recent developments in this field.