The state of the art in Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics Modeling is presented in this new second edition book. It shows how advanced physical and mathematical methods can expand classical models in order to cover heterogeneous drug-biological processes and therapeutic effects in the body. The book is divided into four parts; the first deals with the fundamental principles of fractals, diffusion and nonlinear dynamics; the second with drug dissolution, release, and absorption; the third with epirical, compartmental, and stochastic pharmacokinetic models, with two new chapters, one on fractional pharmacokinetics and one on bioequivalence; and the fourth mainly with classical and nonclassical aspects of pharmacodynamics. The classical models that have relevance and application to these sciences are also considered throughout. This second edition has new information on reaction limited models of dissolution, non binary biopharmaceutic classification system, time varying models, and interface models. Many examples are used to illustrate the intrinsic complexity of drug administration related phenomena in the human, justifying the use of advanced modeling methods. This book will appeal to graduate students and researchers in pharmacology, pharmaceutical sciences, bioengineering, and physiology. Reviews of the first edition: "This book presents a novel modelling approach to biopharmaceutics, pharmacokinetics and pharmacodynamic phenomena. This state-of-the-art volume will be helpful to students and researchers in pharmacology, bioengineering, and physiology. This book is a must for pharmaceutical researchers to keep up with recent developments in this field." (P. R. Parthasarathy, Zentralblatt MATH, Vol. 1103 (5), 2007) "These authors are the unique (or sole) contributors in this area that are working on these questions and bring a special expertise to the field that is now being recognized as essential to understanding biological system and kinetic/dynamic characteristics in drug development...This text is an essential primer for those who would envision the incorporation of heterogeneous approaches to systems where homogeneous approaches are not sufficient to describe the system." (Robert R. Bies, Journal of Clinical Pharmacology, Vol. 46, 2006)

This second edition of a well-received book focuses on rhythmic behaviour in plants, which regulates all developmental and adaptive responses and can thus be regarded as quintessential to life itself. The chapters provide a timely update on recent advances in this field and comprehensively summarize the current state of knowledge concerning the molecular and physiological mechanisms behind circadian and ultradian oscillations in plants, their physiological implications for growth and development and adaptive responses to a dynamic environment. Written by a diverse group of leading researchers, the book will spark the interest of readers from many branches of science: from physicists and chemists wishing to learn about the multi-faceted rhythms in plants, to biologists and ecologists involved in the state-of-the-art modelling of complex rhythmic phenomena.

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.

This volume focuses on Time-Correlated Single Photon Counting (TCSPC), a powerful tool allowing luminescence lifetime measurements to be made with high temporal resolution, even on single molecules. Combining spectrum and lifetime provides a “fingerprint� for identifying such molecules in the presence of a background. Used together with confocal detection, this permits single-molecule spectroscopy and microscopy in addition to ensemble measurements, opening up an enormous range of hot life science applications such as fluorescence lifetime imaging (FLIM) and measurement of Förster Resonant Energy Transfer (FRET) for the investigation of protein folding and interaction. Several technology-related chapters present both the basics and current state-of-the-art, in particular of TCSPC electronics, photon detectors and lasers. The remaining chapters cover a broad range of applications and methodologies for experiments and data analysis, including the life sciences, defect centers in diamonds, super-resolution microscopy, and optical tomography. The chapters detailing new options arising from the combination of classic TCSPC and fluorescence lifetime with methods based on intensity fluctuation represent a particularly unique highlight.

This book discusses geometric and mathematical models that can be used to study fluid and structural mechanics in the cardiovascular system. Where traditional research methodologies in the human cardiovascular system are challenging due to its invasive nature, several recent advances in medical imaging and computational fluid and solid mechanics modelling now provide new and exciting research opportunities. This emerging field of study is multi-disciplinary, involving numerical methods, computational science, fluid and structural mechanics, and biomedical engineering. Certainly any new student or researcher in this field may feel overwhelmed by the wide range of disciplines that need to be understood. This unique book is one of the first to bring together knowledge from multiple disciplines, providing a starting point to each of the individual disciplines involved, attempting to ease the steep learning curve. This book presents elementary knowledge on the physiology of the cardiovascular system; basic knowledge and techniques on reconstructing geometric models from medical imaging; mathematics that describe fluid and structural mechanics, and corresponding numerical/computational methods to solve its equations and problems. Many practical examples and case studies are presented to reinforce best practice guidelines for setting high quality computational models and simulations. These examples contain a large number of images for visualization, to explain cardiovascular physiological functions and disease. The reader is then exposed to some of the latest research activities through a summary of breakthrough research models, findings, and techniques. The book’s approach is aimed at students and researchers entering this field from engineering, applied mathematics, biotechnology or medicine, wishing to engage in this emerging and exciting field of computational hemodynamics modelling.

Cold atmospheric plasma is an auspicious new candidate in cancer treatment. Cold atmospheric plasma (CAP) is a partially ionized gas in which the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules and UV photons. These various compositional elements have the potential to inhibit cancer cell activity whilst doing no harm to healthy cells. Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults; treatment including surgery, radio- and chemotherapy remains palliative for most patients as a cure remains elusive. The successful combination of the standard chemotherapeutic temozolomide (TMZ) and CAP treatment features synergistic effects even in resistant glioma cells. In particular in glioma therapy, CAP could offer an innovative approach allowing specific cancer cell / tumor tissue inhibition without damaging healthy cells. Thus CAP is a promising candidate for combination therapy especially for patients suffering from GBMs showing TMZ resistance.

This volume is essential reading for anyone wishing to understand the recent explosion of experimental tools in neuroscience that now make it possible to manipulate, record, and understand neuronal activity within the intact brain, and which are helping us learn how the many neurons that comprise a network act together to control behavior. Leaders in the field discuss the latest developments in optogenetics, functional imaging, circuit mapping, and the application of these tools to complex biological problems.

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.

This volume describes the state-of-knowledge in the study of the relationships between mechanical loading states in tissues and common pathophysiologies related to increase in mass of adipose tissues and/or hyperglycemia which eventually lead to obesity, diabetes, insulin resistance, hyperlipidemia, metabolic inflammations, certain types of cancer and other related diseases. There appears to be an interaction between the loading states in tissues and cells and these chronic conditions, as well as with factors such as age, gender and genetics of the individual. Bioengineering has made key contributions to this research field in providing technologies for cell biomechanics experimentation, microscopy and image processing, tissue engineering and multi-scale, multi-physics computational modeling. Topics at the frontier of this field of study include: the continuous monitoring of cell growth, proliferation and differentiation in response to mechanical factors such as stiffness of the extracellular matrix (ECM) and mechanical loads transferred through the ECM; mechanically-activated signaling pathways and molecular mechanisms; effects of different loading regimes and mechanical environments on differentiation fates of mesenchymal stem cells (MSCs) into myogenic and osteogenic versus adipogenic lineages; the interactions between nutrition and mechanotransduction; cell morphology, focal adhesion patterns and cytoskeletal remodeling changes in adipogenesis; activation of receptors related to diabetes by mechanical forces; brown and white adipose plasticity and its regulation by mechanical factors.

The proceeding is a collection of research papers presented at the International Colloquium on Sports Science, Exercise, Engineering and Technology (ICoSSEET2014), a conference dedicated to address the challenges in the areas of sports science, exercise, sports engineering and technology including other areas of sports, thereby presenting a consolidated view to the interested researchers in the aforesaid fields. The goal of this conference was to bring together researchers and practitioners from academia and industry to focus on the scope of the conference and establishing new collaborations in these areas. The topics of interest are as follows but are not limited to:1. Sports and Exercise Science * Sports Nutrition * Sports Biomechanics * Strength and Conditioning * Motor Learning and Control * Sports Psychology * Sports Coaching * Sports and Exercise Physiology * Sports Medicine and Athletic Trainer * Fitness and Wellness * Exercise Rehabilitation * Adapted Physical Activity / Disability Sport * Physical Education * Dance, Games and Play 2. Sports Engineering and Technology Application * Sports Equipment Mechanics * Athlete Analysis and Measurement * Instrumentation and Measurement in Sports * Fluid Dynamics in Sports * Computational Modeling in Sports 3. Sports Industry and Management * Sports Event * Sports Management * Sports Tourism * Sports Marketing * Sports Ethics and Law * Sports Sociology * Outdoor and Recreation Management * Inclusive Recreation * Leisure

Imaging and Manipulating Molecular Orbitals celebrates the 60th anniversary of the first image of a single molecule by E. Müller. This book summarizes the advances in the field from various groups around the world who use a broad range of experimental techniques: scanning probe microscopy (STM and AFM), field emission microscopy, transmission electron microscopy, attosecond tomography and photoemission spectroscopy. The book is aimed at those who are interested in the field of molecular orbital imaging and manipulation. Included in the book are a variety of experimental techniques in combination with theoretical approaches which describe the spatial distribution and energies of the molecular orbitals. The goal is to provide the reader with an up-to-date summary on the latest developments in this field from various points of view.

Together, the volumes in this series present all of the data needed at various length scales for a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to nano- and microscopic events in a corrector scheme of regulated mechanism. Therefore, investigation of flows of blood and air in anatomical conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning in quantitative terms. The present volume focuses on macroscopic aspects of the cardiovascular and respiratory systems in pathological conditions, i.e., diseases of the cardiac pump, blood vessels, and airways, as well as their treatments. Only diseases that have a mechanical origin or are associated with mechanical disorders are covered. Local flow disturbances can trigger pathophysiological processes or, conversely, result from diseases of conduit walls or their environment. The ability to model these phenomena is essential to the development and manufacturing of medical devices, which incorporate a stage of numerical tests in addition to experimental procedures.

Combining state-of-the-art research with a strong pedagogic approach, this text provides a detailed and complete guide to the theory, practice and applications of optical tweezers. In-depth derivation of the theory of optical trapping and numerical modelling of optical forces are supported by a complete step-by-step design and construction guide for building optical tweezers, with detailed tutorials on collecting and analysing data. Also included are comprehensive reviews of optical tweezers research in fields ranging from cell biology to quantum physics. Featuring numerous exercises and problems throughout, this is an ideal self-contained learning package for advanced lecture and laboratory courses, and an invaluable guide to practitioners wanting to enter the field of optical manipulation. The text is supplemented by www.opticaltweezers.org, a forum for discussion and a source of additional material including free-to-download, customisable research-grade software (OTS) for calculation of optical forces, digital video microscopy, optical tweezers calibration and holographic optical tweezers.

The International Multidisciplinary Microscopy Congress (INTERM2013) was organized on October 10-13, 2013. The aim of the congress was to bring together scientists from various branches to discuss the latest advances in the field of microscopy. The contents of the congress have been broadened to a more "interdisciplinary" scope, so as to allow all scientists working on related subjects to participate and present their work. These proceedings include 39 peer-reviewed technical papers, submitted by leading academic and research institutions from over 12 countries and representing some of the most cutting-edge research available. The 39 papers are grouped into the following sections: - Applications of Microscopy in the Physical Sciences - Applications of Microscopy in the Biological Sciences

In this book, leading scientists in the fields of sensory biology, neuroscience, physics and engineering explore the basic operational principles and behavioral uses of flow sensing in animals and how they might be applied to engineering applications such as autonomous control of underwater or aerial vehicles. Although humans possess no flow-sensing abilities, countless aquatic (e.g. fish, cephalopods and seals), terrestrial (e.g. crickets and spiders) and aerial (e.g. bats) animals have flow sensing abilities that underlie remarkable behavioral feats. These include the ability to follow silent hydrodynamic trails long after the trailblazer has left the scene, to form hydrodynamic images of their environment in total darkness, and to swim or fly efficiently and effortlessly in the face of destabilizing currents and winds.

Lasers are progressively more used as versatile tools for fabrication purposes. The wide range of available powers, wavelengths, operation modes, repetition rates etc. facilitate the processing of a large spectrum of materials at exceptional precision and quality. Hence, manifold methods were established in the past and novel methods are continuously under development. Biomimetics, the translation from nature-inspired principles to technical applications, is strongly multidisciplinary. This field offers intrinsically a wide scope of applications for laser based methods regarding structuring and modification of materials. This book is dedicated to laser fabrication methods in biomimetics. It introduces both, a laser technology as well as an application focused approach. The book covers the most important laser lithographic methods and various biomimetics application scenarios ranging from coatings and biotechnology to construction, medical applications and photonics.

Quorum sensing (QS) describes a chemical communication behavior that is nearly universal among bacteria. Individual cells release a diffusible small molecule (an autoinducer) into their environment. A high concentration of this autoinducer serves as a signal of high population density, triggering new patterns of gene expression throughout the population. However QS is often much more complex than this simple census-taking behavior. Many QS bacteria produce and detect multiple autoinducers, which generate quorum signal cross talk with each other and with other bacterial species. QS gene regulatory networks respond to a range of physiological and environmental inputs in addition to autoinducer signals. While a host of individual QS systems have been characterized in great molecular and chemical detail, quorum communication raises many fundamental quantitative problems which are increasingly attracting the attention of physical scientists and mathematicians. Key questions include: What kinds of information can a bacterium gather about its environment through QS? What physical principles ultimately constrain the efficacy of diffusion-based communication? How do QS regulatory networks maximize information throughput while minimizing undesirable noise and cross talk? How does QS function in complex, spatially structured environments such as biofilms? Previous books and reviews have focused on the microbiology and biochemistry of QS. With contributions by leading scientists and mathematicians working in the field of physical biology, this volume examines the interplay of diffusion and signaling, collective and coupled dynamics of gene regulation, and spatiotemporal QS phenomena. Chapters will describe experimental studies of QS in natural and engineered or microfabricated bacterial environments, as well as modeling of QS on length scales spanning from the molecular to macroscopic. The book aims to educate physical scientists and quantitative-oriented biologists on the application of physics-based experiment and analysis, together with appropriate modeling, in the understanding and interpretation of the pervasive phenomenon of microbial quorum communication.

Synergetics is the quantitative study of multicomponent systems that exhibit nonlinear dynamics and cooperativity. This book specifically considers basic models of the nonlinear dynamics of molecular systems and discusses relevant applications in biological physics and the polymer sciences. Emphasis is placed on specific solutions to the dynamical equations that correspond to the coherent formation of spatial-temporal structures, such as solitons, kinks and breathers, in particular. The emergence of these patterns in molecular structures provides a variety of information on their structural properties and plays a significant part in energy transfer processes, topological defects, dislocations, and related structure transitions. Real media, in which solitons take the form of solitary waves, are also considered. In this context, the formation of nonlinear waves in a continuous medium described by nonlinear equations is associated with spontaneous breaking of the local symmetry of the homogeneous system, which produces a range of interesting phenomena. A particular feature of this text is its combination of analytic and computational strategies to tackle difficult nonlinear problems at the molecular level of matter.

This book describes a global assessment of stem cell engineering research, achieved through site visits by a panel of experts to leading institutes, followed by dedicated workshops. The assessment made clear that engineers and the engineering approach with its quantitative, system-based thinking can contribute much to the progress of stem cell research and development. The increased need for complex computational models and new, innovative technologies, such as high-throughput screening techniques, organ-on-a-chip models and in vitro tumor models require an increasing involvement of engineers and physical scientists. Additionally, this book will show that although the US is still in a leadership position in stem cell engineering, Asian countries such as Japan, China and Korea, as well as European countries like the UK, Germany, Sweden and the Netherlands are rapidly expanding their investments in the field. Strategic partnerships between countries could lead to major advances of the field and scalable expansion and differentiation of stem cells. This study was funded by the National Science Foundation (NSF), the National Institutes of Health (NIH) and the National Institute of Standards and Technology (NIST).

This book provides a molecular view of membrane transport by means of numerous biochemical and biophysical techniques. The rapidly growing numbers of atomic structures of transporters in different conformations and the constant progress in bioinformatics have recently added deeper insights. The unifying mechanism of energized solute transport across membranes is assumed to consist of the conformational cycling of a carrier protein to provide access to substrate binding sites from either side of a cellular membrane. Due to the central role of active membrane transport there is considerable interest in deciphering the principles of one of the most fundamental processes in nature: the alternating access mechanism. This book brings together particularly significant structure-function studies on a variety of carrier systems from different transporter families: Glutamate symporters, LeuT-like fold transporters, MFS transporters and SMR (RND) exporters, as well as ABC-type importers. The selected examples impressively demonstrate how the combination of functional analysis, crystallography, investigation of dynamics and computational studies has made it possible to create a conclusive picture or more precisely, "a molecular movie". Although we are still far from a complete molecular description of the alternating access mechanism, remarkable progress has been made from static snapshots towards membrane transport dynamics.

The book bridges the gap between existing health physics textbooks and reference material needed by a practicing health physicist as the 21st century progresses. This material necessarily encompasses emerging radiation-generating technologies, advances in existing technology, and applications of existing technology to new areas. The book is written for advanced undergraduate and graduate science and engineering courses. It is also be a useful reference for scientists and engineers.

This volume focuses on latest research in therapeutic devices for cardiovascular, i.e. vascular and valvular and cardiac diseases. In the area of vascular therapies, aspects covered relate to latest research in small-diameter tissue-regenerative vascular grafts, one of the greatest persisting challenges in cardiovascular therapies, stent grafts and endovascular stents for percutaneous arterial interventions. Contributions on valvular therapies focus on tissue engineered and tissue regenerative prosthetic heart valves and valvular prostheses for trans-apical implantation including the challenges posed on the prosthesis design. The section on cardiac diseases aims at covering therapeutic advances for myocardial infarction and prevention of heart failure and on in vivo biomechanics of implantable cardiac pacemaker devices. A further section complements these three areas by presenting constitutive modelling of soft biological tissues of the cardiovascular system, an area imperative for advanced numerical and computational modelling in the development and optimisation of cardiovascular devices and therapies.

This lecture notes book presents how enhanced structural information of biomolecular ions can be obtained from interaction with photons of specific frequency - laser light. The methods described in the book "Laser photodissociation and spectroscopy of mass-separated biomolecular ions" make use of the fact that the discrete energy and fast time scale of photoexcitation can provide more control in ion activation. This activation is the crucial process producing structure-informative product ions that cannot be generated with more conventional heating methods, such as collisional activation. The book describes how the powerful separation capabilities and sensitivity of mass spectrometry (MS) can be combined with the structural insights from spectroscopy by measuring vibrational and electronic spectra of trapped analytes. The implementation of laser-based photodissociation techniques in MS requires basic knowledge of tunable light sources and ion trapping devices. This book introduces the reader to key concepts and approaches in molecular spectroscopy, and the light sources and ion traps employed in such experiments. The power of the methods is demonstrated by spectroscopic interrogation of a range of important biomolecular systems, including peptides, proteins, and saccharides, with laser light in the ultraviolet-visible, and infrared range. The book "Laser photodissociation and spectroscopy of mass-separated biomolecular ions" is an indispensable resource for students and researchers engaged or interested in this emerging field. It provides the solid background of key concepts and technologies for the measurements, discusses state-of-the-art experiments, and provides an outlook on future developments and applications.

Together, the volumes in this series present all of the data needed at various length scales for a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to, and remove carbon dioxide from, the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to nano- and microscopic events in a corrector scheme of regulated mechanism. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems, together with the mathematical tools to describe their functioning in quantitative terms. The present volume focuses on macroscopic aspects of the cardiovascular and respiratory systems in normal conditions, i.e., anatomy and physiology, as well as the acquisition and processing of medical images and physiological signals.

This book focuses on the assembly, organization and resultant collective dynamics of soft matter systems maintained away from equilibrium by an energy flux. Living matter is the ultimate example of such systems, which are comprised of different constituents on very different scales (ions, nucleic acids, proteins, cells). The result of their diverse interactions, maintained using the energy from physiological processes, is a fantastically well-organized and dynamic whole. This work describes results from minimal, biomimetic systems and primarily investigates membranes and active emulsions, as well as key aspects of both soft matter and non-equilibrium phenomena. It is shown that these minimal reconstitutions are already capable of a range of complex behaviour such as nonlinear electric responses, chemical communication and locomotion. These studies will bring us closer to a fundamental understanding of complex systems by reconstituting key aspects of their form and function in simple model systems. Further, they may also serve as the first technological steps towards artificial soft functional matter.