This interdisciplinary thesis introduces a systems biology approach to study the cell fate decision mediated by autophagy. A mathematical model of interaction between Autophagy and Apoptosis in mammalian cells is proposed. In this dynamic model autophagy acts as a gradual response to stress (Rheostat) that delays the initiation of bistable switch of apoptosis to give the cells an opportunity to survive. The author shows that his dynamical model is consistent with existing quantitative measurements of time courses of autophagic responses to cisplatin treatment. To understand the function of this response in cancer cells, he has provided a systems biology experimental framework to study quantitative and dynamical aspects of autophagy in single cancer cells using live-cell imaging and quantitative fluorescence microscopy. This framework can provide new insights on function of autophagic response in cancer cells.

This book describes how biologically available free energy sources (ATP, chemical potential, and membrane potentials, among others) can be used to drive synthetic reactions, signaling in cells, and various types of motion such as membrane traffic, active transport, and cell locomotion. As such, it approaches the concept of the energy cycle of life on Earth from a physical point of view, covering topics ranging from an introduction to chemical evolution, to an examination of the catalytic activity of enzymes associated with the genome in Darwinian evolution. The author introduces the relationship between functions and physical properties in biomembranes, explaining the methods and equipment used in biophysics research to help researchers unravel the still-unsolved mysteries of life. The physical principles needed to understand the cellular functions are provided; these functions are associated with biomembranes and regulated by physical properties of the lipid bilayer such as membrane fluidity, phase transition, and phase separation, as shown in lipid rafts. Other key dynamic aspects of life (cell locomotion, cytoskeletal dynamics, and sensitivities of the cell to physical stimuli such as external forces and temperature) are also discussed. Lastly, readers will learn how life on Earth and its ecological system are maintained by solar energy, and be provided further information on the problems accompanying global warming.

The model-based investigation of motions of anthropomorphic systems is an important interdisciplinary research topic involving specialists from many fields such as Robotics, Biomechanics, Physiology, Orthopedics, Psychology, Neurosciences, Sports, Computer Graphics and Applied Mathematics. This book presents a study of basic locomotion forms such as walking and running is of particular interest due to the high demand on dynamic coordination, actuator efficiency and balance control. Mathematical models and numerical simulation and optimization techniques are explained, in combination with experimental data, which can help to better understand the basic underlying mechanisms of these motions and to improve them. Example topics treated in this book are * Modeling techniques for anthropomorphic bipedal walking systems * Optimized walking motions for different objective functions * Identification of objective functions from measurements * Simulation and optimization approaches for humanoid robots * Biologically inspired control algorithms for bipedal walking * Generation and deformation of natural walking in computer graphics * Imitation of human motions on humanoids * Emotional body language during walking * Simulation of biologically inspired actuators for bipedal walking machines * Modeling and simulation techniques for the development of prostheses * Functional electrical stimulation of walking.

Mass spectrometry is fast becoming an indispensable field for medical professionals. The mass spectrometric analysis of metabolites and proteins promises to revolutionize medical research and clinical diagnostics. As this technology rapidly enters the medical field, practicing professionals and students need to prepare to take full advantage of its capabilities.
Medical Applications of Mass Spectrometry addresses the key issues in the medical applications of mass spectrometry at the level appropriate for the intended readership. It will go a long way to help the utilization of mass spectrometry in medicine.
The book comprises five parts. A general overview is followed by a description of the basic sampling and separation methods in analytical chemistry. In the second part a solid foundation in mass spectrometry and modern techniques of data analysis is presented. The third part explains how mass spectrometry is used in exploring various classes of biomolecules, including proteins and lipids. In the fourth section mass spectrometry is introduced as a diagnostic tool in clinical treatment, infectious pathogen research, neonatal diagnostics, cancer, brain and allergy research, as well as in various fields of medicine: cardiology, pulmonology, neurology, psychiatric diseases, hemato-oncology, urologic diseases, gastrointestinal diseases, gynecology and pediatrics. The fifth part covers emerging applications in biomarker discovery and in mass spectrometric imaging.
* Provides a broad look at how the medical field is benefiting from advances in mass spectrometry.
* Guides the reader from basic principles and methods to cutting edge applications.
* There is NO comparable book on the market to fill this fast growing field.

Nanoneuroscience is the study of computationally relevant biomolecules found inside neurons. Because of recent technological advances at the nanometer scale, scientists have at their disposal increasingly better ways to study the brain and the biophysics of its molecules. This book describes how biomolecules contribute to the operations of synapses and perform other computationally relevant functions inside dendrites. These biomolecular operations considerably expand the brain-computer analogy - endowing each neuron with the processing power of a silicon-based multiprocessor. Amazingly, the brain contains hundreds of billions of neurons.

DNA replication is arguably the most crucial process at work in living cells. It is the mechanism by which organisms pass their genetic information from one generation to the next and life on Earth would be unthinkable without it. Despite the discovery of DNA structure in the 1950s, the mechanism of its replication remains rather elusive. This work makes important contributions to this line of research. In particular, it addresses two key questions in the area of DNA replication: which evolutionary forces drive the positioning of replication origins in the chromosome and how is the spatial organization of replication factories achieved inside the nucleus of a cell?. A cross-disciplinary approach uniting physics and biology is at the heart of this research. Along with experimental support, statistical physics theory produces optimal origin positions and provides a model for replication fork assembly in yeast. Advances made here can potentially further our understanding of disease mechanisms such as the abnormal replication in cancer.

The best way to become acquainted with a subject is to write a book about it. BenjaminDisraeli Cryobiologyisatruemultidisciplinaryscienceinvolvingconceptsfrombiology, medicine, and physics. Its ?eld comprises the study of any biologicalobject or system (e. g. , proteins, cells, tissues, organs, or organisms) under the temp- atures below the normal (ranging from hypothermic conditions to cryogenic temperatures): cold-adaptation of organisms; cryoconservation of biological objects; conservation of organs under hypothermic conditions; lyophilization; cryosurgery. Origins of cryobiology could be traced down to ancient Eg- tians; probably the ?rst scienti?c account of this science is the monograph by Sir Robert Boyle "New Experiments and Observations Touching Cold" (London, 1683). Twentieth century witnessed a rapid development of cryo- ologyrelatedtotheprogressofthecryogenicequipment(closedsystemsbased on liquid nitrogen, Joule-Tohomson cooling with mixed gases, etc. ), devel- ments of monitoring techniques, extension of the list of diseases that have been successfully treated by cryomedicine, and consolidation of research by foundation (simultaneously in 1964) of two major scienti?c societies in this ? eld - The Society for Cryobiology and The Society for Low Temperature Biology. There are a lot of good books on cryobiologythat can be divided into two groups: (1) the ones that treat the whole ?eld of cryobiology - these ones are somewhatout-of-dateand(2)thebooksonspeci?capplicationsofcryobiology such as cryosurgery or cryoconservation.

This book focuses primarily on the role of interfacial forces in understanding biological phenomena at the molecular scale. By providing a suitable statistical mechanical apparatus to handle the biomolecular interface, the book becomes uniquely positioned to address core problems in molecular biophysics. It highlights the importance of interfacial tension in delineating a solution to the protein folding problem, in unravelling the physico-chemical basis of enzyme catalysis and protein associations, and in rationally designing molecular targeted therapies. Thus grounded in fundamental science, the book develops a powerful technological platform for drug discovery, while it is set to inspire scientists at any level in their careers determined to address the major challenges in molecular biophysics. The acknowledgment of how exquisitely the structure and dynamics of proteins and their aqueous environment are related attests to the overdue recognition that biomolecular phenomena cannot be effectively understood without dealing with interfacial behaviour. There is an urge to grasp how biologically relevant behaviour is shaped by the structuring of biomolecular interfaces and how interfacial tension affects the molecular events that take place in the cell. This book squarely addresses these needs from a physicist perspective. The book may serve as a monograph for practitioners and, alternatively, as an advanced textbook. Fruitful reading requires a background in physical chemistry and some basics in biophysics. The selected problems at the end of the chapters and the progression in conceptual difficulty make it a suitable textbook for a graduate level course or an elective course for seniors majoring in chemistry, physics, biomedical engineering or related disciplines.

Fluorescent proteins are intimately connected to research in the life sciences. Tagging of gene products with fluorescent proteins has revolutionized all areas of biosciences, ranging from fundamental biochemistry to clinical oncology, to environmental research. The discovery of the Green Fluorescent Protein, its first, seminal application and the ingenious development of a broad palette of fluorescence proteins of other colours, was consequently recognised with the Nobel Prize for Chemistry in 2008.

"Fluorescent Proteins I" is devoted to the basic photophysical and photochemical aspects of fluorescent protein technology. Experienced experts highlight colour tuning, the exploration of switching phenomena and respective methods for their investigation. The book provides a thorough understanding of primary molecular processes allowing the design of fluorescent proteins for specific applications.

Working in mathematical oncology is a slow and difficult process, requiring the acquisition of a special mindset that goes well beyond the usual applications of mathematics and physics. "Mathematical Oncology 2013" presents the most significant recent results in the field of mathematical oncology, highlighting the work of world-class research teams. This innovative volume emphasizes the way different researchers see and approach problems, not just technical results. It covers many of the most important topics related to the mathematical modeling of tumors, including: Free boundaries. Tumors are growing entities, as such their spatial mean field description involves free boundary problems.Constitutive equations. Tumors should be described as nontrivial porous media.Stochastic dynamics. At the end of anti-cancer therapy, a small number of cells remain, whose dynamics is thus inherently stochastic.Noise-induced state transitions. The growth parameters of macroscopic tumors are non-constant, as are the parameters of anti-tumor therapies. This may induce phenomena that are mathematically equivalent to phase transitions.Stochastic and fractal geometry. Tumor vascular growth is self-similar.

The intended audience consists of graduate students and researchers in the fields biomathematics, computational and theoretical biology, biophysics and bioengineering, where the phenomenon tumor is acquiring the same relevance as in modern molecular biology."

The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. Volume 5 is devoted to cells, tissues, and organs of the cardiovascular and ventilatory systems with an emphasis on mechanotransduction-based regulation of flow. The blood vessel wall is a living tissue that quickly reacts to loads applied on it by the flowing blood. In any segment of a blood vessel, the endothelial and smooth muscle cells can sense unusual time variations in small-magnitude wall shear stress and large-amplitude wall stretch generated by abnormal hemodynamic stresses. These cells respond with a short-time scale (from seconds to hours) to adapt the vessel caliber. Since such adaptive cell activities can be described using mathematical models, a key objective of this volume is to identify the mesoscopic agents and nanoscopic mediators required to derive adequate mathematical models. The resulting biomathematical models and corresponding simulation software can be incorporated into platforms developed in virtual physiology for improved understanding and training.

Disulfide-containing proteins belong to a unique class of proteins for studying the mechanism of protein folding. Their folding mechanism can be analyzed by three distinct techniques: (1) The conventional denaturation-renaturation method (disulfide intact); (2) The disulfide oxidation method (oxidative folding); and (3) The emerging disulfide scrambling method. Each technique provides specific information as to how an unfolded disulfide protein refolds to form the native structure. This book is intended to highlight the knowledge of several important proteins (BPTI, RNase A, beta-Lactalbumin and Lysozyme etc.) that have been characterized in depth by these methodologies. The book will also devote sections to comparing these methodologies and chaperones (PDI and Dsb machineries) that facilitate folding of disulfide proteins. Folding of Disulfide Proteins aims to cover the knowledge of protein folding accumulated from studies of disulfide-containing proteins, including methodologies, folding pathways, and folding mechanism of numerous extensively characterized disulfide proteins. This book will be of interest to those interested in problems related to protein folding, and anyone who is interested in understanding the mechanism of protein misfolding and protein misfolding-related diseases. Folding of Disulfide Proteins aims to cover the knowledge of protein folding accumulated from studies of disulfide-containing proteins, including methodologies, folding pathways, and folding mechanism of numerous extensively characterized disulfide proteins. This book will be of interest to those interested in problems related to protein folding, and anyone who is interested in understanding the mechanism of protein misfolding and protein misfolding-related diseases.

This volume provides a comprehensive selection of recent studies addressing insect hearing and acoustic communication. The variety of signalling behaviours and hearing organs makes insects highly suitable animals for exploring and analysing signal generation and hearing in the context of neural processing, ecology, evolution and genetics. Across a variety of hearing species like moths, crickets, bush-crickets, grasshoppers, cicadas and flies, the leading researchers in the field cover recent scientific progress and address key points in current research, such as:

. How can we approach the evolution of hearing in insects and what is the developmental and neural origin of the auditory organs?

. How are hearing and sound production embedded in the natural lifestyle of the animals, allowing intraspecific communication but also predator avoidance and even predation?

. What are the functional properties of hearing organs and how are they achieved at the molecular, biophysical and neural levels?

. What are the neural mechanisms of central auditory processing and signal generation?

The book is intended for students and researchers both inside and outside of the fascinating field of bioacoustics and aims to foster understanding of hearing and acoustic communication in insects."

DNA (sometimes referred to as the molecule of life), is the most interesting and most important of all molecules. Electrochemistry of Nucleic Acids and Proteins: Towards Electrochemical Sensors for Genomics and Proteomics is devoted to the electrochemistry of DNA and RNA and to the development of sensors for detecting DNA damage and DNA hybridization. Volume 1, in the brand new series Perspectives in Bioanalysis, looks at the electroanalytical chemistry of nucleic acids and proteins, development of electrochemical sensors and their application in biomedicine and in the new fields of genomics and proteomics. The authors have expertly formatted the information for a wide variety of readers, including new developments that will inspire students and young scientists to create new tools for science and medicine in the 21st century.
* Covers highly sophisticated methods of electrochemical analysis of nucleic acids and proteins
* Summarises the present state of electrochemical analysis of nucleic acids and proteins
* Includes future trends in the electrochemical analysis in genomics and proteomics

Availability of advanced computational technology has fundamentally altered the investigative paradigm in the field of biomechanics. Armed with sophisticated computational tools, researchers are seeking answers to fundamental questions by exploring complex biomechanical phenomena at the molecular, cellular, tissue and organ levels. The computational armamentarium includes such diverse tools as the ab initio quantum mechanical and molecular dynamics methods at the atomistic scales and the finite element, boundary element, meshfree as well as immersed boundary and lattice-Boltzmann methods at the continuum scales. Multiscale methods that link various scales are also being developed. While most applications require forward analysis, e.g., finding deformations and stresses as a result of loading, others involve determination of constitutive parameters based on tissue imaging and inverse analysis. This book provides a glimpse of the diverse and important roles that modern computational technology is playing in various areas of biomechanics including biofluids and mass transfer, cardiovascular mechanics, musculoskeletal mechanics, soft tissue mechanics, and biomolecular mechanics.

Caveolae (latin for little caves) are small structures found at the surface of cells. They are responsible for the regulation of important metabolic pathway. As a consequence, they may play a critical role in several human diseases such as atherosclerosis, cancer, diabetes, and muscular dystrophies. This book analyzes the role and function of caveolae in these aspects and serves as the first textbook currently available on caveolae/caveolin.

This book focuses on the application of fluorescence to study motor proteins (myosins, kinesins, DNA helicases and RNA polymerases). It is intended for a large community of biochemists, biophysicists and cell biologists who study a diverse collection of motor proteins. It can be used by researchers to gain an insight into their first experiments, or by experienced researchers who are looking to expand their research to new areas. Each chapter provides valuable advice for executing the experiments, along with detailed background knowledge in order to develop own experiments.

This is the first book that is not exclusively focused on ion channels functioning in sensory mechanisms that are characteristic of animals and humans, but also describes the role of ion channels in signal transduction mechanisms found in microbial cells and plants. It summarizes comprehensively the progress that has been made in studies of ion channels and their role in sensory physiology.

This book provides an introduction to the mathematical aspects of Euler's elastic theory and its application. The approach is rigorous, as well as visually depicted, and can be easily digested. The first few chapters introduce the needed mathematical concepts from geometry and variational calculus. The formal definitions and proofs are always illustrated through complete derivations and concrete examples. In this way, the reader becomes acquainted with Cassinian ovals, Sturmian spirals, co-Lemniscates, the nodary and the undulary, Delaunay surfaces, and their generalizations. The remaining chapters discuss the modeling of membranes, mylar balloons, rotating liquid drops, Hele-Shaw cells, nerve fibers, Cole's experiments, and membrane fusion. The book is geared towards applied mathematicians, physicists and engineers interested in Elastica Theory and its applications.

This work establishes linear-scaling density-functional theory (DFT) as a powerful tool for understanding enzyme catalysis, one that can complement quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics simulations. The thesis reviews benchmark studies demonstrating techniques capable of simulating entire enzymes at the ab initio quantum-mechanical level of accuracy. DFT has transformed the physical sciences by allowing researchers to perform parameter-free quantum-mechanical calculations to predict a broad range of physical and chemical properties of materials. In principle, similar methods could be applied to biological problems. However, even the simplest biological systems contain many thousands of atoms and are characterized by extremely complex configuration spaces associated with a vast number of degrees of freedom. The development of linear-scaling density-functional codes makes biological molecules accessible to quantum-mechanical calculation, but has yet to resolve the complexity of the phase space. Furthermore, these calculations on systems containing up to 2,000 atoms can capture contributions to the energy that are not accounted for in QM/MM methods (for which the Nobel prize in Chemistry was awarded in 2013) and the results presented here reveal profound shortcomings in said methods.

Parkinson's disease is a neurological disorder with cardinal motor signs of resting tremor, bradykinesia and lead-pipe rigidity. In addition, many patients display non-motor symptoms, including a diminished sensation of smell, gastrointestinal problems, various disorders of sleep and some cognitive impairment. These clinical features - particularly the motor signs - manifest after a progressive death of many dopaminergic neurones in the brain. Although currently available, conventional therapies can reduce the signs of the disease, the progression of this neuronal death has proved difficult to slow or stop, and the condition is relentlessly progressive. Hence, there is a real need to develop a treatment that is neuroprotective, one that slows the pathology of the disease effectively. At present, there are several neuroprotective therapies in the experimental pipeline, but these are for the patients of tomorrow. This book focuses on two therapies that are readily available for the patients of today. They involve the use of exercise and light (i.e. photobiomodulation, the use of red to infrared light therapy ( =600-1070nm) on body tissues). The two therapies are tied together in several ways. First, in animal models of Parkinson's disease, they each have been shown to offer the key feature of neuroprotection, stimulating a series of built-in protective mechanisms within the neurones, that helps their survival, to self-protect and/or self-repair. There are also some promising indications of neuroprotection and many beneficial outcomes in parkinsonian patients. Further, both exercise and light therapies are similar in that they are non-invasive and safe to use, with no known adverse side-effects, making their combination with the conventional therapies, such as dopamine replacement drug therapy and deep brain stimulation, all the more feasible. Given the heterogeneity of Parkinson's disease in humans, tackling the condition from a range of different angles - with a number of different therapies - would only serve to enhance the positive outcomes. This book considers the use of exercise and light therapies, proposing that they have the potential to make a powerful "dynamic duo", offering a most effective neuroprotective treatment option to patients.

One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in: (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each of the above mentioned areas of computational modeling. The underlying tissue engineering applications will vary from blood vessels over trachea to cartilage and bone. For the chapters describing examples of the first two areas, the main focus is on (the optimization of) mechanical signals, mass transport and fluid flow encountered by the cells in scaffolds and bioreactors as well as on the optimization of the cell population itself. In the chapters describing modeling contributions in the third area, the focus will shift towards the biology, the complex interactions between biology and the micro-environmental signals and the ways in which modeling might be able to assist in investigating and mastering this complexity. The chapters cover issues related to (multiscale/multiphysics) model building, training and validation, but also discuss recent advances in scientific computing techniques that are needed to implement these models as well as new tools that can be used to experimentally validate the computational results.

This book is the latest volume in a highly successful series within Comprehensive Biochemistry and provides a historical and autobiographical perspective of the development of the field through the contributions of leading individuals who reflect on their careers and their impact on biochemistry. The book is essential reading for everybody, from graduate student to professor, placing in context major advances not only in biochemical terms but in relation to historical and social developments. Readers will be delighted by the lively style and the insight into the lives and careers of leading scientists of their time.

Unlike most natural colours that are based on pigment absorption, the striking iridescent and intense colouration of many butterflies, birds or beetles stems from the interaction of light with periodic sub-micrometer surface or volume patterns, so called "photonic structures". These "structural colours" are increasingly well understood, but they are difficult to create artificially and exploit technologically. In this thesis the field of natural structural colours and biomimetic photonic structures is covered in a wide scope, ranging from plant photonics to theoretical optics. It demonstrates diffractive elements on the petal surfaces of many flowering plant species; these form the basis for the study of the role of structural colours in pollinator attraction. Self-assembly techniques, combined with scale able nanofabrication methods, were used to create complex artificial photonic structures inspired by those found in nature. In particular, the colour effect of a Papilio butterfly was mimicked and, by variation of its design motive, enhanced. All photonic effects described here are underpinned by state-of-the-art model calculations.