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 exhaustive work sheds new light on unsolved questions in gamma-ray astrophysics. It presents not only a complete introduction to the non-thermal Universe, but also a description of the Imaging Atmospheric Cherenkov technique and the MAGIC telescopes. The Fermi-LAT satellite and the HAWC Observatory are also described, as results from both are included. The physics section of the book is divided into microquasars and pulsar wind nebulae (PWNe), and includes extended overviews of both. In turn, the book discusses constraints on particle acceleration and gamma-ray production in microquasar jets, based on the analyses of MAGIC data on Cygnus X-1, Cygnus X-3 and V404 Cygni. Moreover, it presents the discovery of high-energy gamma-ray emissions from Cygnus X-1, using Fermi-LAT data. The book includes the first joint work between MAGIC, Fermi-LAT and HAWC, and discusses the hypothetical PWN nature of the targets in depth. It reports on a PWN population study that discusses, for the first time, the importance of the surrounding medium for gamma-ray production, and in closing presents technical work on the first Large-Size-Telescope (LST; CTA Collaboration), along with a complete description of the camera.

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.

Mathematically, natural disasters of all types are characterized by heavy tailed distributions. The analysis of such distributions with common methods, such as averages and dispersions, can therefore lead to erroneous conclusions. The statistical methods described in this book avoid such pitfalls. Seismic disasters are studied, primarily thanks to the availability of an ample statistical database. New approaches are presented to seismic risk estimation and forecasting the damage caused by earthquakes, ranging from typical, moderate events to very rare, extreme disasters. Analysis of these latter events is based on the limit theorems of probability and the duality of the generalized Pareto distribution and generalized extreme value distribution. It is shown that the parameter most widely used to estimate seismic risk - Mmax, the maximum possible earthquake value - is potentially non-robust. Robust analogues of this parameter are suggested and calculated for some seismic catalogues. Trends in the costs inferred by damage from natural disasters as related to changing social and economic situations are examined for different regions.

The results obtained argue for sustainable development, whereas entirely different, incorrect conclusions can be drawn if the specific properties of the heavy-tailed distribution and change in completeness of data on natural hazards are neglected.

This pioneering work is directed at risk assessment specialists in general, seismologists, administrators and all those interested in natural disasters and their impact on society.

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.

Physical Oceanography of the Dying Aral Sea describes the background, present crisis state, and possible future of this peculiar inland water body from the physical oceanographic standpoint. Based on a wide range of material, a large part of which was published in Russian and has not been previously available to the international reader, the book first provides an historical overview of this unique system, which possesses both lake and sea properties.

Next, the current physical state of the lake is described, partly based on original field research and model experiments, along with the remote sensing data, model results and analyses extracted from recent literature. Next, book attempts to forecast the forthcoming state of the Aral Sea and identify plausible future scenarios. Finally, the book discusses the Aral Sea dessication viewd as a part of the global perspective.

Providing the most comprehensive, up-to-date coverage of this exciting biomedical field, Handbook of Photomedicine gathers together a large team of international experts to give you a complete account of the application of light in healthcare and medical science. The book progresses logically from the history and fundamentals of photomedicine to diverse therapeutic applications of light, known collectively as phototherapies. It facilitates your understanding of human diseases caused by light, the rationale for photoprotection, and major applications of phototherapy in clinical practice. The handbook begins with a series of historical vignettes of pioneers from the last two centuries. It also presents the fundamentals of physics and biology as applied to photomedicine. It next examines conditions and diseases caused by light, including skin cancer, dermatoses, and immunosuppression. The remainder of the book focuses on the most important clinical therapeutic applications of different kinds of light that vary in both wavelength and intensity. The book discusses ultraviolet phototherapy for skin diseases and infections and presents the basic science of photodynamic therapy and its use in cancer therapy and other medical specialties. It then covers mechanistic studies and clinical applications of low-level laser (light) therapy as well as the use of high power or surgical laser therapy in specialties, such as dentistry and dermatology. The book concludes with a collection of miscellaneous types of phototherapy.

This book focuses on essential theories, methods and techniques in the field of environmental and engineering geophysics that can contribute to resource detection and environmental protection. Geophysics has been playing an important role in exploring the earth, locating vital resources and promoting the development of society. This book covers a range of topics including the exploration of modern resources, such as ore deposits, coal mines, shale gas and geothermal power, and the monitoring of geological disasters, including the rock-soil body, ground deformation, mines, specific rock-soil engineering disasters, desertification of land and environmental abnormalities. This book not only offers a valuable resource for geophysical researchers; it also demonstrates how geophysics theories and methods can be practically implemented to protect our environment and promote the development of human society.

This book elaborates on the acceleration of charged particles with ultrafast terahertz electromagnetic radiation. It paves the way for new, and improves many aspects of current, accelerator applications. These include providing shorter electron bunches for ultrafast time-resolved pump-probe spectroscopy, enabling complex longitudinal profiles to be imparted onto charged particle bunches and significantly improving the ability to synchronise an accelerator to an external laser. The author has developed new sources of terahertz radiation with attractive properties for accelerator-based applications. These include a radially biased large-area photoconductive antenna (PCA) that provided the largest longitudinally polarised terahertz electric field component ever measured from a PCA. This radially biased PCA was used in conjunction with an energy recovery linear accelerator for electron acceleration experiments at the Daresbury Laboratory. To achieve even higher longitudinally polarised terahertz electric field strengths, and to be able to temporally tune the terahertz radiation, the author investigated generation within non-linear optical crystals. He developed a novel generation scheme employing a matched pair of polarity inverted magnesium-oxide doped stoichiometric lithium niobate crystals, which made it possible to generate longitudinally polarised single-cycle terahertz radiation with an electric field amplitude an order of magnitude larger than existing sources.

Impact cratering is an important geological process on all solid planetary bodies, and, in the case of Earth, may have had major climatic and biological effects. Most terrestrial impact craters have been erased or modified beyond recognition. However, major impacts throw ejecta over large areas of the Earth's surface. Recognition of these impact ejecta layers can help fill in the gaps in the terrestrial cratering record and at the same time provide direct correlation between major impacts and other geological events, such as climatic changes and mass extinctions. This book provides the first summary of known distal impact ejecta layers

Schumann resonance has been studied for more than half a century. The field became popular among researchers of the terrestrial environment using natural sources of electromagnetic radiation-lightning strokes, primarily-and now many Schumann observatories have been established around the world. A huge number of publications can be found in the literature, the most recent collection of which was presented in a special Schumann resonance section of the journal Radio Science in 2007. The massive publications, however, impede finding information about how to organize measurements and start observations of global electromagnetic resonance. Relevant information is scattered throughout many publications, which are not always available. The goal of this book is to collect all necessary data in a single edition in order to describe the demands of the necessary equipment and the field-site as well as the impact of industrial and natural interference, and to demonstrate typical results and obstacles often met in measurements. The authors not only provide representative results but also describe unusual radio signals in the extremely low-frequency (ELF) band and discuss signals in the adjacent frequency ranges.

This book deals with the astrophysics and spectroscopy of the interstellar molecules. In the introduction, overview and history of interstellar observations are described in order to help understanding how the modern astrophysics and molecular spectroscopy have been developed interactively. The recent progress in the study of this field is briefly summarized. Furthermore, the basic knowledge of molecular spectroscopy, which is essential to correctly comprehend the astrophysical observations, is presented in a compact form.

Polymers are essential to biology because they can have enough stable degrees of freedom to store the molecular code of heredity and to express the sequences needed to manufacture new molecules. Through these they perform or control virtually every function in life. Although some biopolymers are created and spend their entire career in the relatively large free space inside cells or organelles, many biopolymers must migrate through a narrow passageway to get to their targeted destination. This suggests the questions: How does confining a polymer affect its behavior and function? What does that tell us about the interactions between the monomers that comprise the polymer and the molecules that confine it? Can we design and build devices that mimic the functions of these nanoscale systems? The NATO Advanced Research Workshop brought together for four days in Bikal, Hungary over forty experts in experimental and theoretical biophysics, molecular biology, biophysical chemistry, and biochemistry interested in these questions. Their papers collected in this book provide insight on biological processes involving confinement and form a basis for new biotechnological applications using polymers. In his paper Edmund DiMarzio asks: What is so special about polymers? Why are polymers so prevalent in living things? The chemist says the reason is that a protein made of N amino acids can have any of 20 different kinds at each position along the chain, resulting in 20 N different polymers, and that the complexity of life lies in this variety.

This book summarizes the theoretical and experimental studies confirming the concept of the liquid-crystalline nature of boundary lubrication in synovial joints. It is shown that cholesteric liquid crystals in the synovial liquid play a significant role in the mechanism of intra-articular friction reduction. The results of structural, rheological and tribological research of the creation of artificial synovial liquids containing cholesteric liquid crystals in natural synovial liquids are described. These liquid crystals reproduce the lubrication properties of natural synovia and provide a high chondroprotective efficiency. They were tested in osteoarthritis models and in clinical practice.

Cosmic rays consist of elementary particles with enormous energy which originate from outside our solar system and constantly hit the Earth's atmosphere. Where do these cosmic rays originate? How does nature accelerate the cosmic-ray particles to energies with orders of magnitude beyond the limits of manmade particle accelerators? What can we learn by measuring the interactions of the cosmic rays with the atmosphere? Digital radio-antenna arrays offer a promising, complementary measurement method for high-energy cosmic rays. This thesis reports on substantial advances in the development of the radio technique, which will be used to address these questions in future experiments.

This book is a synopsis of modern deep-field astronomy, based on the powerful telescopes and instruments developed in recent years. It is organized along topical themes, such as the extragalactic background radiation at different wavelengths, the evolution of galaxies, the history of star formation, the nature of absorbers, the reionization of the intergalactic medium, the validity of photometric redshifts, gravitational lensing, and clustering of galaxies. Stellar and substellar objects were not neglected, however, and one session was devoted to nearby bodies such as trans-Neptunian solar system objects, brown dwarfs, and stars with special characteristics.

This thesis adopts the relative back-projection method to dramatically reduce "swimming" artifacts by identifying the rupture fronts in the time window of a reference station; this led to a faster and more accurate image of the rupture processes of earthquakes. Mitigating the damage caused by earthquakes is one of the primary goals of seismology, and includes saving more people's lives by devising seismological approaches to rapidly analyze an earthquake's rupture process. The back-projection method described in this thesis can make that a reality.

The origin of the most energetic particles observed in nature is one of the major unresolved questions in modern astrophysics. Theoretical speculations range from electromagnetic acceleration in some unknown astrophysical source to as yet undiscovered particle physics beyond the Standard Model. These speculations have also lead to the development of new detection concepts and experimental projects, some of which are currently under construction. The present volume consists of a self-contained set of lectures which cover most of these aspects: from the speculative origins and the acceleration and propagation mechanisms to a discussion of the detection techniques. It emphasizes the strong interdisciplinarity of this topic and highlights the many open questions. This volume is intended for students entering this field and for professional astronomers and particle and theoretical physicists.

This books aims at giving an overview over theoretical and phenomenological aspects of particle astrophysics and particle cosmology. To be of interest for both students and researchers in neighboring fields of physics, it keeps a balance between well established foundations that will not significantly change in the future and a more in-depth treatment of selected subfields in which significant new developments have been taking place recently. These include high energy particle astrophysics, such as cosmic high energy neutrinos, the interplay between detection techniques of dark matter in the laboratory and in high energy cosmic radiation, axion-like particles, and relics of the early Universe such as primordial magnetic fields and gravitational waves. It also contains exercises and thus will be suitable for both introductory and advanced courses in astroparticle physics.

The utilization of refrigeration and cryogenics contributes to high-quality preservation and processing of foods, in environmental protection, and in case of emergencies. Refrigerating and cryogenic engineering enhance progress in machine-building and automation of manufacturing processes, while refrigeration and cryogenics are increasingly used in construction. Refrigerating engineering is the backbone of the air-conditioning industry.

This dictionary covers all of these aspects: it presents terminology that is used in thermodynamics and transport, as well as terminology depicting the use of refrigeration and cryogenics in the chemical and mining industries and in low-temperature physics. It contains basic terminology on refrigerating machinery, heat-transfer processes and heat-exchange equipment, refrigerating plants, cold-storage warehouses, refrigerating commercial equipment, and units.

Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection.
Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada, the USA and Australia.
This booksummarizes the advances achieved by these research groups after more than ten years of studies on radiation damage in biomolecular systems.

An extensive Part I deals with recent experimental and theoretical findings on radiation induced damage at the molecular level. It includes many contributions on electron and positroncollisions with biologically relevant molecules. X-ray and ion interactions are also covered. Part II addresses different approaches to radiation damage modelling. In Part III biomedical aspects of radiation effects are treated on different scales. After the physics-oriented focus of the previous parts, there is a gradual transition to biology and medicine with the increasing size of the object studied. Finally, Part IV is dedicated to current trends and novel techniques in radiation reserach and the applications hence arising. It includes new developments in radiotherapy and related cancer therapies, as well as technical optimizations of accelerators and totally new equipment designs, giving a glimpse of the near future of radiation-based medical treatments."