This book addresses the important clinical problem of accurately diagnosing osteoporosis, and analyzes how Bone Turnover Markers (BTMs) can improve osteoporosis detection. In her research, the author integrated microfluidic technology with electrochemical sensing to embody a reaction/detection chamber to measure serum levels of different biomarkers, creating a microfluidic proteomic platform that can easily be translated into a biomarker diagnostic. The Osteokit System, a result of the integration of electrochemical system and microfluidic chips, is a unique design that offers the potential for greater sensitivity. The implementation, feasibility, and specificity of the Osteokit platform is demonstrated in this book, which is appropriate for researchers working on bone biology and mechanics, as well as clinicians.

This Volume presents protocols for investigating the genetic, metabolic and ecological potential and functional analysis of microbial communities. Methods are described for the creation and bioinformatic assessment of metagenomic and metatranscriptomic libraries, and for metaproteomic analyses, which provide important insights into the metabolic potential and interactions of community members. These in turn lead to specific hypotheses concerning the functional contributions of individual populations in the community, which may be investigated by the stable isotope probing approaches described in this Volume, making it possible to identify those community members primarily responsible for particular functions. Methods for the direct extraction of proteins from environmental samples for sequencing and activity tests are presented, providing a broad overview of prevailing metabolic activities and of the types of microbe involved in them. Protocols for the analysis of nutrient flow through microbial communities and for the modelling of dynamic physiological interactions in communities are also provided. Lastly, the book presents a protocol for the quantitative assessment of permissiveness for the transfer of conjugative plasmids, important agents of physiological change and evolution in microbial communities. Hydrocarbon and Lipid Microbiology ProtocolsThere are tens of thousands of structurally different hydrocarbons, hydrocarbon derivatives and lipids, and a wide array of these molecules are required for cells to function. The global hydrocarbon cycle, which is largely driven by microorganisms, has a major impact on our environment and climate. Microbes are responsible for cleaning up the environmental pollution caused by the exploitation of hydrocarbon reservoirs and will also be pivotal in reducing our reliance on fossil fuels by providing biofuels, plastics and industrial chemicals. Gaining an understanding of the relevant functions of the wide range of microbes that produce, consume and modify hydrocarbons and related compounds will be key to responding to these challenges. This comprehensive collection of current and emerging protocols will facilitate acquisition of this understanding and exploitation of useful activities of such microbes.

This book spans diverse aspects of modified nucleic acids, from chemical synthesis and spectroscopy to in vivo applications, and highlights studies on chemical modifications of the backbone and nucleobases. Topics discussed include fluorescent pyrimidine and purine analogs, enzymatic approaches to the preparation of modified nucleic acids, emission and electron paramagnetic resonance (EPR) spectroscopy for studying nucleic acid structure and dynamics, non-covalent binding of low- and high-MW ligands to nucleic acids and the design of unnatural base pairs. This unique book addresses new developments and is designed for graduate level and professional research purposes.

This Volume presents relevant single-cell and single-molecule approaches in the study of microbes producing and utilizing hydrocarbons and lipids. While generically applicable for all microorganisms, the approaches described are, wherever possible, adapted to the field of study of hydrocarbon and lipid microbiology. The methods include basic procedures for isolating single cells by means of microfluidics and flow cytometry, and their cultivation in arrays as pure clones; for isolating, amplifying and sequencing single-cell genomes and transcriptomes; and for analysing single-cell metabolomes by means of Raman spectroscopy. Single-molecule approaches include the use of protein:fluorescent dye fusions for protein localization and methods for the production of cell division protostructures and lipid monolayers. Methods for the functional analysis of single cells include detection of metabolically active (protein-synthesizing) cells in environmental samples by bioorthogonal non-canonical amino acid tagging, Raman spectroscopy combined with stable isotope labelling and fluorescent in situ hybridisation, and visualization of single cells participating in gene transfer activity. Lastly, protocols are presented for single-cell biotechnological applications, including biofuel production. Hydrocarbon and Lipid Microbiology ProtocolsThere are tens of thousands of structurally different hydrocarbons, hydrocarbon derivatives and lipids, and a wide array of these molecules are required for cells to function. The global hydrocarbon cycle, which is largely driven by microorganisms, has a major impact on our environment and climate. Microbes are responsible for cleaning up the environmental pollution caused by the exploitation of hydrocarbon reservoirs and will also be pivotal in reducing our reliance on fossil fuels by providing biofuels, plastics and industrial chemicals. Gaining an understanding of the relevant functions of the wide range of microbes that produce, consume and modify hydrocarbons and related compounds will be key to responding to these challenges. This comprehensive collection of current and emerging protocols will facilitate acquisition of this understanding and exploitation of useful activities of such microbes.

Significantly extended from the first edition, this book presents the basics of microbiologically influenced corrosion (MIC) in an accessible and concise manner. It explores strategies for recognizing, understanding, mitigating and preventing this type of corrosion, and investigates this topic from the point of view of an engineer. Chapters cover issues including stress corrosion cracking and microbial corrosion, the pros and cons of biocides, the involvement of magnetic bacteria in microbial corrosion, and cathodic protection based on recent research in microbial environments. The 2nd Edition provides new material examining the following topics: *The corrosion-related bacteria clostridia *Mathematical modelling of MIC, in particular fuzzy logic *A comparison of culture-independent methods with culture-dependent methods *Further practical strategies for dealing with MIC *Natural biocidesThis book has provided course material for the author's microbial corrosion workshops around the world, and it presents an invaluable resource to corrosion and integrity professionals working in a wide range of industries including power generation, oil and gas, marine, and mining. It is also intended for students and academics of corrosion engineering, materials science, microbiology, chemical engineering and welding.

This book introduces the most recent innovations in natural polymer applications in the food, construction, electronics, biomedical, pharmaceutical, and engineering industries. The authors provide perspectives from their respective range of industries covering classification, extraction, modification, and application of natural polymers from various sources in nature. They discuss the techniques used in analysis of natural polymers in various systems incorporating natural polymers as well as their intrinsic properties.

Die Kombination bereits verfugbarer Polymere zu Polymermischungen (Blends) erlaubt durch Nutzung ohnehin vorhandener Anlagentechnik wie Extrudern oder Knetern die ausserst schnelle und kostengunstige Anpassung der Werkstoffeigenschaften an das Anforderungsprofil einer geplanten Anwendung. Werden zusatzlich Nanopartikel zugesetzt, konnen Struktur-und Funktionswerkstoffe mit einzigartigen Eigenschaften hergestellt werden. Dies gilt insbesondere bei Verwendung von Carbon Nanotubes, die seit ihrer erstmaligen detaillierten Beschreibung im Jahr 1991 einen der grossten Forschungshypes der modernen Werkstoffentwicklungsgeschichte ausgelost haben. Nach der Verarbeitung bestimmt die raumliche Anordnung der Nanopartikel innerhalb der eingefrorenen Blendphasen die Werkstoffeigenschaften der Blendkomposite. Die Kenntnis der wahrend des Schmelzemischens massgeblichen Lokalisierungsmechanismen ist somit der Schlussel zum Verstandnis der Eigenschaften dieser Werkstoffe. Hauptgegenstand der vorliegenden Arbeit ist die Aufklarung des Lokalisierungsverhaltens von mehrwandigen Carbon-Nanotubes (MWCNTs) beim Schmelzemischen mit zweiphasigen Polymermischungen. Dies umfasst sowohl die Phanomenologie von Transfervorgangen zwischen den Blendphasen als auch die Ursachen des Grenzflachenubertritts. Es wird gezeigt, dass sich das Lokalisierungsverhalten von Carbon Nanotubes grundlegend von jenem anderer Nanopartikel wie z.B. Carbon Black unterscheidet. Dabei wird es von sehr starken thermodynamischen Kraften bestimmt, die in der Regel die hochselektive Anordnung der Nanotubes in einer der Blendphasen bewirken. Dieses Phanomen konnte auf die Geometrie der Nanopartikel zuruckgefuhrt werden. Es wird zudem nachgewiesen, dass CNTs trotz der starken, in die besser benetzende Phase gerichteten thermodynamischen Triebkrafte auch hochselektiv in einer schlechter benetzenden Phase angeordnet werden konnen, wenn es gelingt, die aussere Hulle der CNTs kovalent an diese anzubinden. Es wird gezeigt, dass d

Process synthesis and process intensification are becoming state-of-the-art scientific fields that provide the methods and tools to improve process technologies in terms of high energy efficiency, low capital investment, low emissions, improved safety, and less hazardous byproducts to achieve sustainable products and processes. The book covers manufacturing processes from both fossil- and biomass-based feedstocks for graduate students.

This is a new book on food process engineering which treats the principles of processing in a scientifically rigorous yet concise manner, and which can be used as a lead in to more specialized texts for higher study. It is equally relevant to those in the food industry who desire a greater understanding of the principles of the food processes with which they work. This text is written from a quantitative and mathematical perspective and is not simply a descriptive treatment of food processing. The aim is to give readers the confidence to use mathematical and quantitative analyses of food processes and most importantly there are a large number of worked examples and problems with solutions. The mathematics necessary to read this book is limited to elementary differential and integral calculus and the simplest kind of differential equation.

This volume provides the technical information required for the production of biofuels and chemicals from lignocellulosic biomass. It starts with a brief overview of the importance, applications, and production processes of different lignocellulosic products. Further chapters review the perspectives of waste-based biofuels and biochemicals; the pretreatment of lignocellulosic biomass for biofuel production; cellulolytic enzyme systems for the hydrolysis of lignocelluloses; and basic and applied aspects of the production of bioethanol, biogas, biohydrogen, and biobutanol from lignocelluloses. This book is recommended for researchers and engineers and particularly students taking biofuel courses at graduate level.

The safety and efficacy of minimal food processing depends on the use of novel preservation technologies. This book first examines what is meant by minimally processed foods, including fresh-cut, cooked-chilled, and part-baked products. Next explored are the technologies or methods to produce quality products in terms of safety and nutrition, including: edible coating, natural preservatives (i.e., antimicrobial, flavour enhancer, anti-browning), advanced packaging (active, antimicrobial, and modified or controlled atmosphere), and selected non-thermal techniques (high pressure, pulsed electric field, ultrasound, light). Preservation of food is crucial to achieving a secure and safe global food supply with the desired sensory quality. In addition, the increasing consumer demand for safe, ready-to-serve, ready-to-eat-and-cook products with minimal chemical preservatives has raised expectations. However, foods deemed minimally processed, such as fresh-cut fruits and vegetables, cooked-chilled, and half-baked foods, are delicate products that need special care in preparation, processing, storage, and handling. As a result, new technologies to develop minimally processed foods have aggressively advanced. Minimally Processed Foods: Technologies for Safety, Quality, and Convenience explores both the definition of minimally processed foods and the methods and technologies used to achieve the safety and nutritional value consumers demand. About the Editors Mohammed Wasim Siddiqui, Bihar Agricultural University, Sabour, Bhagalpur, India Mohammad Shafiur Rahman, Sultan Qaboos University, Al-khod, Oman

Glyco-engineering is being developed as a method to control the composition of carbohydrates and to enhance the pharmacological properties of monoclonal antibodies (mAbs) and other proteins. In Glycosylation Engineering of Biopharmaceuticals: Methods and Protocols, experts in the field provide readers with production and characterization protocols of glycoproteins and glyco-engineered biopharmaceuticals with a focus on mAbs. The volume is divided in four complementary parts dealing with glyco-engineering of therapeutic proteins, glycoanalytics, glycoprotein complexes characterization, and PK/PD assays for therapeutic antibodies. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Glycosylation Engineering of Biopharmaceuticals: Methods and Protocols serves as an ideal guide for scientists striving to push forward the exciting field of engineered biopharmaceuticals.

Since the discovery of the pharmacological and toxicological importance of inhibiting the cyclooxygenase (COX) enzymes by non-steroidal anti-inflammatory drugs (NSAIDs), much research has gone into the development of methods to study the biological functions of COX-1 and COX-2. In Cyclooxygenases: Methods and Protocols, experts and pioneers in the field present the most up-to-date in vitro and in vivo techniques routinely used in COX research. The volume delves into essential topics such as the purification, cloning, and expression of COX enzymes as well as in vitro assays aimed at determining the inhibitory potency of drugs on COX-1 and COX-2 activities, with chapters describing protocols used for the extraction and measurement of the prostanoids. This volume also describes in vivo disease models used to study the roles of COX-1 and COX-2 in gastrointestinal injury, inflammation, and pain. As a book in the highly successful Methods in Molecular Biology (TM) series, the protocols chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Cyclooxygenases: Methods and Protocols serves as an indispensable tool for all scientists seeking the treatment of inflammation, pain, fever, and other harmful conditions.

The use of Instant Controlled Pressure Drop (D.I.C.) in food processing operations is relatively new when compared with other conventional or innovative technologies. In addition to existing applications such as drying, texturing and decontamination, D.I.C. technology has been shown to be highly appropriate for an ever-growing number of uses and with a wide range of raw materials. Some examples are post-harvesting and drying of fruits and vegetables; cereal steaming; extraction of essential oils and active molecules, where D.I.C. may be combined with supercritical fluids, ultrasound or microwaves; and the hydrolysis of cellulose and the transesterification of lipids. This book presents a complete picture of current knowledge on the use of D.I.C. in food processing, preservation and extraction. It provides a comprehensive compilation, summarizing the fundamentals of D.I.C. technology, current developments, new research findings, safety precautions and environmental impacts. It will also contribute to widening the scope of D.I.C. technology through the inclusion of some much-needed examples of industrial applications. Each chapter of the book is complementary to the other chapters. They all are based on presentations of reputed international researchers and address the latest progress in the field. Professor Karim ALLAF heads a research team working on the intensification of eco-processes at La Rochelle University. He is a physicist and an expert in the thermodynamics of "instantaneity". Dr. Tamara ALLAF is the R&D manager of ABCAR-DIC Process Company. A chemical engineer, she obtained her Ph.D. in innovative extraction processes.

The seafood processing industry produces a large amount of by-products that usually consist of bioactive materials such as proteins, enzymes, fatty acids, and biopolymers. These by-products are often underutilized or wasted, even though they have been shown to have biotechnological, nutritional, pharmaceutical, and biomedical applications. For example, by-products derived from crustaceans and algae have been successfully applied in place of collagen and gelatin in food, cosmetics, drug delivery, and tissue engineering. Divided into four parts and consisting of twenty-seven chapters, this book discusses seafood by-product development, isolation, and characterization, and demonstrates the importance of seafood by-products for the pharmaceutical, nutraceutical, and biomedical industries.

Metabolic engineering is the practice of genetically optimizing metabolic and regulatory networks within cells to increase production and/or recovery of certain substance from cells. In Microbial Metabolic Engineering: Methods and Protocols expert researchers in the field detail many of the methods which are now commonly used to study metabolic engineering. These include methods and techniques to engineer genes and pathways, use of modern biotechnology tools in microbial metabolic engineering, and examples of metabolic engineering for real world applications such as whole cell biosensors and acetate control in large scale fermentation. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Microbial Metabolic Engineering: Methods and Protocols seeks to provide researchers with an overview of key topics on microbial metabolic engineering.

Prospective Isolation and Characterization of Human Bone Marrow-Derived MSCs, by A. Harichandan, K. Sivasubramaniyan, H.-J. Buhring Urine as a Source of Stem Cells, by Christina Benda, Ting Zhou, Xianming Wang, Weihua Tian, Johannes Grillari, Hung-Fat Tse, Regina Grillari-Voglauer, Duanqing Pei, Miguel A. Esteban Expansion of Mesenchymal Stem/Stromal Cells under Xenogenic-Free Culture Conditions, by Sven Kinzebach, Karen Bieback Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications, by Danielle Minteer, Kacey G Marra, J Peter Rubin Potential for Osteogenic and Chondrogenic Differentiation of MSC, by Antonina Lavrentieva, Tim Hatlapatka, Anne Neumann, Birgit Weyand, Cornelia Kasper Potential for Neural Differentiation of Mesenchymal Stem Cells, by Letizia Ferroni, Chiara Gardin, Ilaria Tocco, Roberta Epis, Alessandro Casadei, Vincenzo Vindigni, Giuseppe Mucci, Barbara Zavan Migratory Properties of Mesenchymal Stem Cells, by Thomas Dittmar, Frank Entschladen Dissecting Paracrine Effectors for Mesenchymal Stem Cells, by Stefania Bruno, Federica Collino, Ciro Tetta, Giovanni Camussi Proteomics Approaches in the Identification of Molecular Signatures of Mesenchymal Stem Cells, by Yin Xiao, Jiezhong Chen Does the Adult Stroma Contain Stem Cells?, by Richard Schafer

With increasing energy prices and the drive to reduce CO2 emissions, food industries are challenged to find new technologies in order to reduce energy consumption, to meet legal requirements on emissions, product/process safety and control, and for cost reduction and increased quality as well as functionality. Extraction is one of the promising innovation themes that could contribute to sustainable growth in the chemical and food industries. For example, existing extraction technologies have considerable technological and scientific bottlenecks to overcome, such as often requiring up to 50% of investments in a new plant and more than 70% of total process energy used in food, fine chemicals and pharmaceutical industries. These shortcomings have led to the consideration of the use of new "green" techniques in extraction, which typically use less solvent and energy, such as microwave extraction. Extraction under extreme or non-classical conditions is currently a dynamically developing area in applied research and industry. Using microwaves, extraction and distillation can now be completed in minutes instead of hours with high reproducibility, reducing the consumption of solvent, simplifying manipulation and work-up, giving higher purity of the final product, eliminating post-treatment of waste water and consuming only a fraction of the energy normally needed for a conventional extraction method. Several classes of compounds such as essential oils, aromas, anti-oxidants, pigments, colours, fats and oils, carbohydrates, and other bioactive compounds have been extracted efficiently from a variety of matrices (mainly animal tissues, food, and plant materials). The advantages of using microwave energy, which is a non-contact heat source, includes more effective heating, faster energy transfer, reduced thermal gradients, selective heating, reduced equipment size, faster response to process heating control, faster start-up, increased production, and elimination of process steps. This book will present a complete picture of the current knowledge on microwave-assisted extraction (MAE) of bioactive compounds from food and natural products. It will provide the necessary theoretical background and details about extraction by microwaves, including information on the technique, the mechanism, protocols, industrial applications, safety precautions, and environmental impacts.

Thermo-fluid Dynamics of Two-Phase Flow, Second Edition is focused on the fundamental physics of two-phase flow. The authors present the detailed theoretical foundation of multi-phase flow thermo-fluid dynamics as they apply to: Nuclear reactor transient and accident analysis; Energy systems; Power generation systems; Chemical reactors and process systems; Space propulsion; Transport processes. This edition features updates on two-phase flow formulation and constitutive equations and CFD simulation codes such as FLUENT and CFX, new coverage of the lift force model, which is of particular significance for those working in the field of computational fluid dynamics, new equations and coverage of 1 dimensional drift flux models and a new chapter on porous media formulation.

This book provides a broad introduction to all major aspects of quantum dot properties including fluorescence, electrochemical, photochemical and electroluminescence. Such properties have been produced for applications in biosensing, cell tracking, in vivo animal imaging and so on. It focuses on their special applications in DNA biosensing and provides readers with detailed information on the preparation and functionalization of quantum dots and the fabrication of DNA biosensors, using examples to show how these properties can be used in DNA biosensor design and the advantages of quantum dots in DNA biosensing. Further new emerging quantum dots such as metal nanoclusters and graphene dots and their applications in DNA biosensing have also been included.

Contents: Gerard Jaouen, Nils Metzler-Nolte : Introduction ; Stephane GIBAUD and Gerard JAOUEN: Arsenic - based drugs: from Fowler's solution to modern anticancer chemotherapy; Ana M. Pizarro, Abraha Habtemariam and Peter J. Sadler : Activation Mechanisms for Organometallic Anticancer Complexes; Angela Casini, Christian G. Hartinger, Alexey A. Nazarov, Paul J. Dyson : Organometallic antitumour agents with alternative modes of action; Elizabeth A. Hillard, Anne Vessieres, Gerard Jaouen : Ferrocene functionalized endocrine modulators for the treatment of cancer; Megan Hogan and Matthias Tacke : Titanocenes - Cytotoxic and Anti-Angiogenic Chemotherapy Against Advanced Renal-Cell Cancer; Seann P. Mulcahy and Eric Meggers : Organometallics as Structural Scaffolds for Enzyme Inhibitor Design; Christophe Biot and Daniel Dive : Bioorganometallic Chemistry and Malaria; Nils Metzler-Nolte : Biomedical applications of organometal-peptide conjugates; Roger Alberto : Organometallic Radiopharmaceuticals; Brian E. Mann : Carbon Monoxide - an essential signaling molecule.

Research in the pharmaceutical industry today is in many respects quite different from what it used to be only fifteen years ago. There have been dramatic changes in approaches for identifying new chemical entities with a desired biological activity. While chemical modification of existing leads was the most important approach in the 1970s and 1980s, high-throughput screening and structure-based design are now major players among a multitude of methods used in drug discov ery. Quite often, companies favor one of these relatively new approaches over the other, e.g., screening over rational design, or vice versa, but we believe that an intelligent and concerted use of several or all methods currently available to drug discovery will be more successful in the medium term. What has changed most significantly in the past few years is the time available for identifying new chemical entities. Because of the high costs of drug discovery projects, pressure for maximum success in the shortest possible time is higher than ever. In addition, the multidisciplinary character of the field is much more pronounced today than it used to be. As a consequence, researchers and project managers in the pharmaceutical industry should have a solid knowledge of the more important methods available to drug discovery, because it is the rapidly and intelligently combined use of these which will determine the success or failure of preclinical projects.

Aero engine bearing chambers are complex machine elements inside the engines, supporting up to three concentric shafts on bearings. For safety reasons, the aero engines always employ rolling-element type bearings and therefore require a sufficient oil supply for lubrication in order to guarantee a reliable operation. As a consequence, a complex two-phase flow consisting of oil and sealing air governs the bearing chambers. A highly dynamic oil film, flowing along the chamber walls, plays a vital role to fulfill the tasks of cooling, lubricating and cleaning the bearing chambers. The design and optimization process of the bearing chambers requires a detailed understanding in order to accurately simulate the film behaviour inside the bearing chambers. Based on the earlier experimental investigations, it is known that near the scavenge off-take a relatively thick film exists. The numerical model to simulate these films must therefore take into account the elliptical behaviour of such films. Among the different models, the Volume Of Fluid (VOF) Model offers the best compromise between accuracy and efforts. However, preliminary attempts to model a fully developed and turbulent test case from literature revealed an unphysical pressure drop and velocity profile in the gas phase above the film flow. An inadequate turbulence modelling near the gas-liquid interface was identified as the problem source. The 2-Equation turbulence models (k- epsilon & k- omega) were extended to achieve a substantial improvement.

The analysis and modification of glycans of recombinant proteins continues to be active and challenging area of research and for the successful manufacture of these proteins. In Cell Engineering, volume 3: Glycosylation, Dr. Mohammed Al-Rubeai has compiled a group of articles that will provide research workers not only with reviews of the advances that have been made in all facets of the subject but with an in-depth assessment of the state of the art methodology and the various approaches for the improvement of glycoprotein production. Particularly important in this respect is the advances made in the development of genetically engineered host cell lines with novel glycosylation properties, as well as the integration of mass spectrophotometric analysis with separation techniques.

This volume is intended not only for research students and senior scientists in cell culture and glycobiology, but also for industrial biotechnologists and biochemical engineers interested in the production of therapeutic glycoproteins, virus vector and ex vivo expansion of human cells for medical treatment.

More then 20 years have passed now since the first recombinant protein producing microorganisms have been developed. In the meanwhile, numerous proteins have been produced in bacteria, yeasts and filamentous fungi, as weIl as higher eukaryotic cells, and even entire plants and animals. Many recombinant proteins are on the market today, and some of them reached substantial market volumes. On the first sight one would expect the technology - including the physiology of the host strains - to be optimised in detail after a 20 year's period of development. However, several constraints have limited the incentive for optimisation, especially in the pharmaceutical industry like the urge to proceed quickly or the requirement to define the production parameters for registration early in the development phase. The additional expenses for registration of a new production strain often prohibits a change to an optimised strain. A continuous optimisation of the entire production process is not feasible for the same reasons.