Experimental determination of free-energy landscape of a molecule Short-lived states during a defined reaction visualized, without the need for chemical intervention Both methods can be implemented in all labs practicing cryo-EM of biomolecules Original articles and reviews based on research in the author’s lab Currently the only book in the literature covering these subjects

The concept of molecular machines in biology has transformed the medical field in a profound way. Many essential processes that occur in the cell, including transcription, translation, protein folding, and protein degradation, are all carried out by molecular machines. This volume focuses on important molecular machines whose architecture is known and whose functional principles have been established by tools of biophysical imaging (X-ray crystallography and cryo-electron microscopy) and fluorescence probing (single-molecule FRET). This edited volume includes contributions from prominent scientists and researchers who understand and have explored the structure and functions of these machines. This book is essential for students and professionals in the medical field who want to learn more about molecular machines.

Approaches to the recovery of three-dimensional information on a biological object, which are often formulated or implemented initially in an intuitive way, are concisely described here based on physical models of the object and the image-formation process. Both three-dimensional electron microscopy and X-ray tomography can be captured in the same mathematical framework, leading to closely-related computational approaches, but the methodologies differ in detail and hence pose different challenges. The editors of this volume, Gabor T. Herman and Joachim Frank, are experts in the respective methodologies and present research at the forefront of biological imaging and structural biology. Computational Methods for Three-Dimensional Microscopy Reconstruction will serve as a useful resource for scholars interested in the development of computational methods for structural biology and cell biology, particularly in the area of 3D imaging and modeling.

This definitive work provides a comprehensive treatment of the mathematical background and working methods of three-dimensional reconstruction from tilt series. Special emphasis is placed on the problems presented by limitations of data collection in the transmission electron microscope.

The book, extensively revised and updated, takes the reader from biological specimen preparation to three-dimensional images of the cell and its components.

The book reproduces 55 of more than 300 articles written by the author, representing milestones in methods development of single-particle cryo-EM as well as important results obtained by this technique in the study of biological macromolecules and their interactions. Importantly, neither symmetries nor ordered arrangements (as in two-dimensional crystals, helical assemblies, icosahedral viruses) are required. Although the biological applications are mainly in the area of ribosome structure and function, the elucidation of membrane channel structures and their activation and gating mechanisms are represented, as well. The book is introduced by a commentary that explains the original development of concepts, describes the contributions of the author's colleagues and students, and shows how challenges were overcome as the technique matured. Along the way, the ribosome served as an example for a macromolecule with intricate structure and conformational dynamics that pose challenges for three-dimensional visualization. Toward the end of the book - bringing us to the present time - molecular structures with near-atomic resolution are presented, and a novel type of computational analysis, manifold embedding, is introduced.Single-particle cryo-EM is currently revolutionizing structural biology, presenting a powerful alternative to X-ray crystallography as a means to solve the structure of biological macromolecules. The book presents in one place a number of articles containing key advances in mathematical and computational methods leading up to the present time. Secondly, the development of the technique over the years is reflected by ever-expanding discoveries in the field of ribosome structure and function. Thirdly, as all histories of ideas, the history of concepts pertaining to this new method of visualization is fascinating all in itself.

This book provides a complete introduction to both the practical details and the theoretical foundations required in order to use electron microscopy as a research tool in structural biology. Planned and written by a group of 5 well-known experts who have pioneered different aspects of the field of electron cryo-microscopy (cryo-EM) of biological macromolecules, this book offers a depth of knowledge and expertise that could only be replicated from the primary literature with great difficulty. Figures and illustrations are used liberally to simplify the understanding of concepts and to provide ready access to examples of biological applications. In addition, numerous boxes provide auxiliary information for those who wish to go more deeply into areas of background with which they may not already be familiar. The organization of topics lends itself well to using this book either to gain a comprehensive mastery of all aspects of the field of cryo-EM or as an authoritative reference source for individual topics within the field.

Cryoelectron microscopy of biological molecules is among the hottest growth areas in biophysics and structural biology at present, and Frank is arguably the most distinguished practitioner of this art. CryoEM is likely over the next few years to take over much of the structural approaches currently requiring X-ray crystallography, because one can now get good and finely detailed images of single molecules down to as little as 200,000 MW, covering a substantial share of the molecules of greatest biomedical research interest. This book, the successor to an earlier work published in 1996 with Academic Press, is a natural companion work to our forthcoming book on electron crystallography by Robert Glaeser, with contributions by six others, including Frank. A growing number of workers will employ CryoEM for structural studies in their own research, and a large proportion of biomedical researchers will have a growing interest in understanding what the capabilities and limits of this approach are.

"Menschenkenntnis" gehort zu den Themen, uber die man sich im allgemeinen wenig Gedanken macht. Die meisten Menschen halten sich fur gute Menschenkenner und denken selten an die Moglichkeit eines eigenen Irrtums. Anderen Menschen dagegen traut man einen Irrtum viel eher zu. Fast jeder meint, irgendwann einmal selber falsch beurteilt worden zu sein. Denken wir nur an die Schulzeit zu ruck Hat uns nicht der eine oder der andere Lehrer verkannt? Schon aus dieser Uberlegung heraus sollte man seine eigene Men schenkenntnis einmal kritisch betrachten und sich fragen, wieso ein Urteil falsch, ein anderes richtig ist. Diese Frage wird auf den folgenden Seiten ausfuhrlich erortert, und Sie werden sehen, dass unzuverlassige Beurteilungen viel haufiger sind, als man allgemein annimmt. Das Buch gliedert sich in zwei Teile: Im ersten Teil wird gezeigt, wie fragwurdig die allgemein ubliche Vorgehensweise bei der Menschen beurteilung ist, und es werden einige Hinweise zur Verbesserung unserer Urteile gegeben. Der zweite Teil enthalt die Beschreibung einer Methode der Menschenbeurteilung, die es erlaubt, allmahlich zu wesentlich treffenderen Urteilen uber andere Menschen zu kom men. Eine solche dem ublichen Vorgehen uberlegene Methode ist in den Situationen unerlasslich, die zuverlassige Beurteilungen erfordern."

Obwohl es zu den alltaglichen Pfiichten der meisten Verantwort lichen in Betrieben und anderen Organisationen gehort, andere Men schen zu beurteilen, wird bisher noch wenig fUr eine zweckmaI3ige Ausbildung der "Beurteiler" getan. Wir hoffen, daB durch die vor liegende Schrift diese Ausbildungsliicke mit verhaltnismaI3ig wenig Aufwand geschlossen werden kann. Mit dieser Schrift wollen wir die Vorteile des zu beliebigen Zeiten greifbaren Buches mit den Vorziigen eines Lehrgespraches ver binden. Es ist deshalb eine moderne (programmierte) Form der Unterweisung gewahlt worden, bei der jeder Leser entsprechend den bei ihm gegebenen Voraussetzungen seinen eigenen Weg durch das Buch wahlt. Der Inhalt des Buches entspricht einem Ausbildungsplan, der sich in mehr als zehnjahriger psychologischer Schulungstatigkeit in Wirt schaft und Verwaltung als Grundlage fUr eine Verbesserung des innerbetrieblichen Beurteilungswesens bewahrt hat. Es soll nicht nur eine hohere Treffsicherheit der Urteile und damit eine effektvollere Personallenkung erreicht werden, sondern es soll gleichermaBen bei der Personalfiihrung Willkiir verringert und Gerechtigkeit gesteigert werden. Die Autoren danken allen Betrieben und Dienststellen, in denen Er fahrungen - auch mit den Erprobungsfassungen der vorliegenden Schrift - gesammelt werden konnten. Sie danken fUr wertvolle An regungen, die sie in kritischen Gesprachen mit den Dozenten der Wirtschaftsakademie Berlin und ihrem Direktor Dr. H. F. Gross er halten haben. Besonderer Dank richtet sich an die Diplom-Psycholo gen W. Pleger und G. Voss fUr ihre Unterstiitzung bei der Gestaltung der vorliegenden Fassung."