bluuebunny/crossref_metadata_2025 huggingface dataset:
Creep Properties of SUS304 Steel by Small Punch Creep Tests
Authors: Chen Gang , Zhai Peng Cheng , Zhang Qing Jie
Published: October 2009

Creep behavior of SUS304 stainless steel is studied by small punch creep (SP-C) test. Series of SP-C testing for SUS304 stainless steel are carried out at 600°C. The time dependence of the central deflection is obtained by the SP-C testing at different load level and the creep deflection curves are quantitatively similar to those observed in conventional uniaxial creep testing. In this paper, an analytic approach based on Chakrebarty’s membrane-stretch model is used to interpret the SP-C test method. The relationship between specimen central deflection and equivalent strain is deduced, and the relationship between load and equivalent stress are established. The creep stress exponent of SUS304 stainless steel is determined by the theory formula and the data obtained in the SP-C testing. Comparison of the creep stress exponent of the Norton equations in SP-C testing and conventional creep testing is performed. The results show that the creep stress exponent is well consistent with conventional experimental results.
Hypersonic Flutter Analysis of Functionally Graded Panels under Thermal and Aerodynamic Loads
Authors: Kim Sun Bae , Kim Ji Hwan
Published: October 2009

In this work, hypersonic aero-thermo post-buckling and thermal flutter behaviors of Functionally Graded (FG) panels under thermal and aerodynamic loads are investigated. The volume fractions of constitutive materials of the panels are gradually varied from ceramic to metal in the thickness direction based on a simple power law distribution. Thus, the material properties of the panel are also changed by a linear rule of mixture. Furthermore, the material properties are assumed to be temperature dependent because the panels are mainly used in the high temperature environments. Using the principle of virtual work, the equations of motion of the first-order shear deformation plate theory (FSDPT) are derived and the finite element method is applied to get the solution. In the formulation, the von Karman strain-displacement relationship is used for structural nonlinearity, and the partial second-order piston theory is adopted to consider the aerodynamic nonlinearity. Newton-Raphson iterative technique is used to solve the governing equations, and linear eigenvalue analysis is performed to obtain the hypersonic flutter boundaries.
Selected Interlayer of Diamond Deposition on γ-TiAl Intermetallic Compounds Prepared by Microwave-Plasma Assisted CVD
Authors: Abu Suilik Saleh B. , Ohshima Masayuki , Tetsui Toshimitsu , Hasezaki Kazuhiro
Published: October 2009

Several diamond coatings were performed on -TiAl substrates by a microwave-plasma assisted CVD, which were made directly to the substrate and indirectly to the TiC, Ti5Si3, Al2O3+TiO2 and Si layers on the substrate. The direct coatings suffered from severe delamination and cracks. The deposited layers on TiC and Ti5Si3 layers partially delaminated, while those on Al2O3+TiO2 and Si layers adhered well without delamination. All the diamond films deposited were characterized using scanning electron microscopy, Raman spectroscopy, and X-ray diffraction. Raman spectra showed that poly- and nano-crystalline diamond films were obtained for the coatings of -TiAl.
Asphalt Pavement Aging and Temperature Dependent Properties through a Functionally Graded Viscoelastic Model, Part-I: Development, Implementation and Verification
Authors: Dave Eshan V. , Paulino Glaucio H. , Buttlar William G.
Published: October 2009

Asphalt concrete pavements are inherently graded viscoelastic structures. Oxidative aging of asphalt binder and temperature cycling due to climatic conditions are the major cause of such graded non-homogeneity. Current pavement analysis and simulation procedures either ignore or use a layered approach to account for non-homogeneities. For instance, the recently developed Mechanistic-Empirical Design Guide (MEPDG) [1], which was recently approved by the American Association of State Highway and Transportation Officials (AASHTO), employs a layered analysis approach to simulate the effects of material aging gradients through the depth of the pavement as a function of pavement age. In the current work, a graded viscoelastic model has been implemented within a numerical framework for the simulation of asphalt pavement responses under various loading conditions. A functionally graded generalized Maxwell model has been used in the development of a constitutive model for asphalt concrete to account for aging and temperature induced property gradients. The associated finite element implementation of the constitutive model incorporates the generalized iso-parametric formulation (GIF) proposed by Kim and Paulino [2], which leads to the graded viscoelastic elements proposed in this work. A solution, based on the correspondence principle, has been implemented in conjunction with the collocation method, which leads to an efficient inverse numerical transform procedure. This work is the first of a two-part paper and focuses on the development, implementation and verification of the aforementioned analysis approach for functionally graded viscoelastic systems. The follow-up paper focuses on the application of this approach.
Interpenetrating Network Metal-Ceramic FGM – Preparation and Properties
Authors: Neukam Matthias , Willert-Porada Monika
Published: October 2009

A new method for processing large flat compositionally graded metal-ceramic parts with connected interpenetrating metal and ceramic network is described. Based on powder metallurgical methods, a metal foam is obtained by slip casting of metal powder slurries on a polyurethane foam, and used as preform to achieve a metallic interpenetration within the composite. The porous metallic preform is infiltrated with a ceramic slip and co-sintered. The metallic part is made from Ni-Cr-alloy, or the P/M superalloy Saratherm 2 and Nimonic 90, the ceramic consists of pure 8Y-ZrO2 or zirconia mixed with ZrSiO4. Composites of nominal same composition sintered without the metal foam preform show no metallic interpenetration.
Prototype Design and Evaluation of Lightweight Mirror and Wavelength Selective Filter for Space Solar Power Systems
Authors: Kisara Katsuto , Suzuki Kazuyuki , Ishikawa Toichiro , Fujita Kazuhisa , Masumoto Hiroshi
Published: October 2009

The large scale SSPS (Space Solar Power System) needs large reflection mirrors for sunlight concentration. To use film mirror in space, the mirror must have lightweight structures and resistive to harsh space environment. The wavelength selective filter to avoid heat is a dielectric multilayer film which has FGM structure. In this article, we will report the development of a lightweight wavelength selective mirror and wavelength selection on the solar light excitation laser.
Microassembly of Artificial Crystals by Inter-Particle Laser Welding and Optical Characterization
Authors: Takagi Kenta , Omote Masanori , Kawasaki Akira
Published: October 2009

To fabricate artificial crystals with any structure from monosized spherical particles, we have so far manufactured a three-dimensionally particle assembling system with a combination of pick-and-place robotic manipulation and inter-particle laser welding. In the present study, we aimed to assemble large-scale artificial crystals of polyethylene (PE) particles by mean of the new system. In this method, an optimization of the laser welding conditions was indispensable for the strong bonding with maintaining the shape of particles. Thus, the two-particle welding tests were preliminarily conducted. On the basis of this result, we successfully assembled the large-scale artificial crystals with diamond structure from the PE -ceramic or -carbon composite particles. In order to discuss applicability of the obtained crystals to terahertz (THz) wave photonic crystals, the transmittance spectrum of the crystals was evaluated by a THz wave time domain spectroscopy. The PE-ceramic particle crystal presented an ideal photonic band gap which perfectly agreed with the theoretical one.
Asphalt Pavement Aging and Temperature Dependent Properties through a Functionally Graded Viscoelastic Model, Part-II: Applications
Authors: Dave Eshan V. , Buttlar William G. , Paulino Glaucio H.
Published: October 2009

This is the second article in a series of two papers describing simulation of functionally graded viscoelastic properties in asphalt concrete pavements. The techniques developed are applicable to other viscoelastic material systems with continuous, spatial grading of material properties. A full-depth asphalt concrete pavement has been simulated to demonstrate the applicability and importance of the graded viscoelastic analysis method. Based on the graded finite elements developed by Kim and Paulino[1], Buttlar et al. [2] used graded finite elements to determine typical responses to tire loading for an aged asphalt concrete pavement. In the current study, a similar pavement section is studied using the viscoelastic graded analysis (rather than elastic). Graded, layered and homogeneous material variations were used for a series of simulations, and the results from different approaches were compared.
Thermodynamics of FGM: New Approach for Free Energy and the Equilibrium State Calculations
Authors: Gasik Michael M. , Bilotsky Yevgen , Lev Bohdan
Published: October 2009

FGM thermodynamics has been mostly based on adaptation of classical Gibbs-Helmholtz approach for infinite systems to locally “homogeneous” zones. A statistical sum calculation in this theory cannot predict inhomogeneous distributions. A new approach to the statistical description of solid solutions is suggested, which takes into account possible formation of spatially inhomogeneous simultaneous particle and field distributions in finite space domains. The formation of new periodical or gradated structure in binary system is described. The effective free energy of system was determined and the condition of formation of such spatially inhomogeneous distribution of interacting particles was obtained. New method may be applied to FGM to calculate ab initio free energy of these systems without usual limitations of classical theory.
Development of Novel Functionally Graded Al2O3-Lanthanum Hexaaluminate Ceramics for Thermal Barrier Coatings
Authors: Negahdari Zahra , Willert-Porada Monika , Scherm Florian
Published: October 2009

Lanthanum hexaaluminate (LHA) has superior thermo-chemical stability at temperatures higher than 1000 °C and is a promising competitor to Y-ZrO2-based thermal barrier coatings (TBCs). The yet unresolved problem is control of microstructure of high LHA content ceramics and adjustment of porosity upon, to arrive at a material exhibiting low thermal conductivity at high temperature combined with structural reliability. Therefore, a functionally graded alumina/lanthanum hexaaluminate (FGLHA) with a gradient in composition was developed. The thermal diffusivity and thermal conductivity of FGLHA were compared with the one of the monolithic composite ceramics. The alumina-rich composites showed excellent mechanical properties whereas the LHA-rich composites presented lower thermal conductivity.
Adipocytes as Immune Cells: Differential Expression of TWEAK, BAFF, and APRIL and Their Receptors (Fn14, BAFF-R, TACI, and BCMA) at Different Stages of Normal and Pathological Adipose Tissue Development
Authors: Alexaki Vassilia-Ismini , Notas George , Pelekanou Vassiliki , Kampa Marilena , Valkanou Maria , Theodoropoulos Panayiotis , Stathopoulos Efstathios N. , Tsapis Andreas , Castanas Elias
Published: October 2009

Adipose tissue represents a rich source of multipotent stem cells. Mesenchymal cells, isolated from this source, can differentiate to other cell types in vitro and therefore can be used for a number of regenerative therapies. Our view of adipose tissue has recently changed, establishing adipocytes as new members of the immune system, as they produce a number of proinflammatory cytokines (such as IL-6 and TNFα and chemokines, in addition to adipokines (leptin, adiponectin, resistin) and molecules associated with the innate immune system. In this paper, we report the differential expression of TNF-superfamily members B cell activating factor of the TNF Family (BAFF), a proliferation inducing ligand (APRIL), and TNF-like weak inducer of apoptosis (TWEAK) in immature-appearing and mature adipocytes and in benign and malignant adipose tissue-derived tumors. These ligands act through their cognitive receptors, BAFF receptor, transmembrane activator and calcium signal-modulating cyclophilic ligand (TACI), B cell maturation Ag (BCMA), and fibroblast growth factor-inducible 14 (Fn14), which are also expressed in these cells. We further report the existence of functional BCMA, TACI, and Fn14 receptors and their ligands BAFF, APRIL, and TWEAK on adipose tissue-derived mesenchymal cells, their interaction modifying the rate of adipogenesis. Our data integrate BAFF, APRIL, and TWEAK and their receptors BCMA, TACI, and Fn14 as novel potential mediators of adipogenesis, in addition to their specific role in immunity, and define immature and mature adipocytes as source of immune mediators.
Identification of a Flavin Mononucleotide Module Residue Critical for Activity of Inducible Nitrite Oxide Synthase
Authors: Liu Xian-De , Mazumdar Tuhina , Xu Yi , Getzoff Elizabeth D. , Eissa N. Tony
Published: October 2009

Inducible NO synthase (iNOS) contains an amino-terminal oxygenase domain, a carboxy-terminal reductase domain, and an intervening calmodulin-binding domain. For the synthesis of NO, iNOS is active as a homodimer formed by oxygenase domains, while the reductase domain is required to transfer electrons from NADPH. In this study, we identify glutamate 658 in the FMN domain of human iNOS to be a critical residue for iNOS activity and we explore the underlying mechanism for such role. Mutation of glutamate to aspartate almost abolished iNOS activity and reduced dimer formation. Substitution of this residue with noncharged alanine and glutamine, or positively charged lysine did not affect dimer formation and maintained around 60% of iNOS activity. These results suggest that the negative charge specific to glutamate plays an important role in iNOS activity.
Closure of a Giant Saphenous Vein Graft Aneurysm with Embolization Coil
Authors: Kumar Ashwani , Santana Dixon , Jenkins Leigh Ann
Published: October 2009

Aneurysms of saphenous vein grafts (SVGs) to coronary arteries are rare, usually asymptomatic and found incidentally. We report a case of an 84-year-old female who was found to have 8.1 8.4 cm aneurysm of an SVG to obtuse marginal (OM) artery. The aneurysm was prior to the distal anastamosis but no flow into the OM artery was noted. Cook Tornado Embolization Coils were used successfully to occlude the SVG proximal to the aneurysm. No complications occurred. The use of embolization coils is an effective and safe method for aneurysm occlusion when the anatomy is suitable and especially when patient is high risk for repeat surgical intervention.
Adsorption, Proteins with Synthetic Materials
Authors: Mcguire Joseph , Joshi Omkar
Published: October 2009

The surfaces of materials of almost any type that come into contact with protein mixtures tend to become quickly occupied by proteins. Adsorbed proteins can differ substantially in structure and function from their counterparts in solution. In addition, protein layers lead to alterations in the properties of the material–fluid interface, affecting material performance in a number of bioprocess and biomedical applications. Performance of immobilized enzyme bioreactors, purification of therapeutic proteins in modern biotechnology, drug formulation strategies, bacterial adhesion and contamination of industrial process equipment, and cell adhesion to natural and synthetic materials in the body, are only a few examples of processes affected by protein behavior at interfaces. An important impediment to needed progress in all of these areas continues to be our inability to predict what the eventual makeup and nature of these layers will be under a given set of conditions. Protein interactions with solid surfaces have been studied for decades, and several reviews are available. In this treatment we describe some generally well understood, important results that have provided a basis for meeting the challenges facing engineers and scientists in this area. Emphasis is placed on the driving forces for protein adsorption, the rate and extent of post‐adsorptive events undergone by proteins adsorbed from single‐ and multiprotein solutions, and surfactant modulation of protein adsorption.
Affinity Fusions: Gene Expression
Authors: Gräslund Susanne , Hammarström Martin
Published: October 2009

In response to the rapidly growing field of proteomics, the use of recombinant proteins has increased greatly in recent years. Since proteins have very diverse physiological properties, they are not naturally adjusted to generic methods. Affinity tags, providing a common handle for all kinds of proteins, have consequently become indispensable tools for structural and functional analysis of whole proteomes. Although originally developed to facilitate the detection and purification of recombinant proteins, it has become clear in recent years that affinity tags can also have positive impact on the yield, solubility,
in vivo
half‐life, and even the folding of their fusion partners. However, no single affinity tag is optimal with respect to all these parameters. Each has its strengths and weaknesses and therefore a suitable tag must be chosen for each application. An alternative would be the use of combinatorial tags and thus combining several desired properties.
Aflatoxins
Authors: Yu Jiujiang , Chang Perng‐Kuang , Cleveland Thomas E. , Bennett Joan W.
Published: October 2009

Aflatoxins are toxic and carcinogenic secondary metabolites produced primarily by the filamentous fungiAspergillus flavusandAspergillus parasiticus. Aflatoxin biosynthesis is a complex process involving many intermediates and enzymes, which are regulated at multiple levels. Owing to its complexity and importance, scientists from biochemistry, molecular biology and genetics are attracted to the study of its mechanisms of biosynthesis and regulation. These efforts have resulted in significant process in the last decade. We present here a review of the present knowledge of the aflatoxin biosynthetic pathway, pathway enzymes, and the genes encoding these enzymes involved in the conversion of major aflatoxin intermediates. Genes confirmed to be involved in regulation of aflatoxin formation and control of aflatoxin contamination are summarized as well.
Aldehyde Reductase
Authors: Shimizu Sakayu , Kataoka Michihiko
Published: October 2009

The properties of an aldehyde reductase, belonging to the aldo‐keto reductase superfamily, are descried. The novel microbial aldehyde reductase can be used as a catalyst for the stereospecific production of chiral alcohols.
Amino Acid Production:L‐Lysine
Authors: Nagai Yuri , Ito Hisao , Yasueda Hisashi
Published: October 2009

L‐Lysine is an essential amino acid for humans and animals and is exclusively used as a feed additive for swine and poultry throughout the world, since most grains used for the feed are deficient inL‐lysine in nutritional amino acid balance. This amino acid has been extensively produced by fermentation using gram‐positive coryneform bacteria includingCorynebacterium glutamicum. To date, many studies on strain improvement have been carried out using various methods including conventional mutagenesis and screening, genetic engineering, and metabolic engineering. Recently, the complete genome sequence ofC. glutamicumhas been determined, and the genetic information is very valuable for strain development for higher performance, in coordination with various “omics” analyses. BesidesC. glutamicum, other bacteria includingEscherichia colihave also been considered as promising producers of amino acids with high interest. Together with strain development, the improvements of fermentation and purification technologies also contribute to the success of the industrial production ofL‐lysine. It is estimated that the current annual production ofL‐lysine is more than 850,000 metric tons throughout the world.
Animal Cell Types andB‐Cell Lineage
Authors: Walker Kenneth Barry , Rodgers Angela
Published: October 2009

B cells are fundamentally important cells in immune responses and the production of immunoglobulins. They have a complex developmental pathway and have a unique gene rearrangement capability providing a wide repertoire of antigen recognition that encompasees most possible epitope combinations available in nature. These cells and the antibodies they produce have been developed into useful clinical applications through the development of monoclonal antibodies, and studies of the cells themselves have revealed much about the biology of cell maturation and gene regulation.

This article provides an overview of the biology and activities of these cellsin vivoalong with their applications and uses in the laboratory and sources of cell lines for research and potential applications.
Animal Cell Types, Monocyte, Macrophage and Dendrite Lineage
Authors: Rodgers Angela , Walker Kenneth Barry
Published: October 2009

Monocytes, macrophages, and dendritic cells are generated from progenitor bone marrow stem cells. These cells are found in anatomically diverse regions, where they display various functions and phenotypes, which facilitate their involvement in both the innate and adaptive immune responses. The functions and importance of these cells in immune responses have been ascertained by examining specific cell lines andin vitroculture of defined isolated cell types. An overview of these cells is detailed here with consideration of their uses for definingin vivofunctions and, particularly for dendritic cells, harnessing their potential to dampen or develop better immune responses.
Basidiomycetous Yeasts for Production of Carotenoids
Authors: Buzzini Pietro , Goretti Marta , Branda Eva , Turchetti Benedetta
Published: October 2009

WhileSaccharomyces cerevisiaeis the most widely exploited yeast in biotechnology, it cannot be forgotten that this species represents only a small percentage of blastomycetes biodiversity. Currently, in fact, numerous other species are being utilized or studied for potentially important roles such as many basidiomycetous yeasts. Nevertheless, in spite of their enormous biosynthetic potential, studies regarding their many useful catalytic attributes and products are still primarily confined to the laboratory.

The ability of some basidiomycetous yeast to produce and accumulate carotenoids as intracellular pigments is well known. The astaxanthin‐producing speciesXanthophyllomyces dendrorhous(formerlyPhaffia rhodozyma) is by far the most famous carotenoid‐synthesizing yeast. Although the occurrence of astaxanthin in yeasts appears to be confined to this species, others, belonging to the generaRhodotorula,Rhodosporidium,Sporobolomyces, andSporidiobolus, have been shown to produce various important carotenoids such as β‐carotene, γ‐carotene, torulene, and torularhodin.
Beer Brewing, Applications of Metabolic Engineering
Authors: Piddocke Maya , Olsson Lisbeth
Published: October 2009

Currently, beer is one of the beverage products with the largest annual production worldwide of 1767 million hL in 2007 alone, with lager beer production accounting for 90% of the total beer produced. The present drivers for technological improvement in brewing are increased industrial competition and consolidation, constant demand for increased productivity and flexibility, and the need for achieving high quality together with low costs and compliance with environmental policies. Using metabolic engineering strategies, improvements in the brewer's yeast fermentation performance has involved increased attenuation rate, improved control of the production of beer flavor metabolites, increased ethanol yields and osmotolerance for high‐gravity beer fermentations, and reduced ethanol yield for low or zero alcohol beer production. With the availability of theSaccharomyces cerevisiaegenome sequence, together with the bioinformatics tools enabling integration and interrogation of largex‐omicsdata sets, it is possible to identify high‐probability targeted genetic or metabolic strategies to increase yield, titer, productivity, and/or robustness of the existing brewing process. As the use of GMO strains in brewing is not accepted, mutagenesis remains the alternative approach for obtaining brewer's yeast variants with superior performances. However, the use of enzymes, often products of genetically modified strains, for brewing process optimization is currently recognized. As brewing is a product‐based process, introduction of new technologies for process optimization such as high‐gravity brewing and continuous fermentation using immobilized yeast in brewing lead to improved economics without change in the product characteristics and quality.
Biofilters, Air Purification
Authors: Zilli Mario , Kennes Christian , Veiga María C. , Converti Attilio
Published: October 2009

For economic and safety reasons, biofiltration is now recognized as one of the most advantageous treatment technologies available to control odors, volatile organic compounds (VOCs), and toxic air emissions from diverse municipal and industrial sources, provided the volatile compound does not need to be recovered and when the pollutant concentration does not exceed 5–10 g/m3. It is considered a clean technology with minimal energy requirements and low waste production.

This article reviews the history and current state of the biofiltration technology, summarizes its principles, design, and operation, and discusses the applicability of biofiltration systems for a wide variety of specific emission sources. Moreover, an overview of the key factors influencing biofilter design, operation, and performance is provided.

A comparison with other biological systems outlines that conventional biofilters have the easiest mode of operation combined with quite a wide application range and relatively low capital and operating costs.

A wide picture of the biofilter applications either at pilot‐scale or full‐scale with related pollutants that can be removed is given. The results reported show that, under proper conditions, biofilters can offer high removal efficiencies for a wide range of common air pollutants.

The principal groups of microorganisms involved in biofilters as well as their respective main metabolic pathways are also presented and discussed.

Economic analysis made on different bases demonstrates that biofiltration is by far the most convenient process if applied to high flow rates of air emissions containing relatively low concentrations of easily biodegradable compounds.

Finally, current and potential future developments of the biofiltration technology are also addressed.
Bionanofabrication of Nanostructures and Functional Materials
Authors: Sierra‐Sastre Yajaira , Mark Sonny S. , Niamsiri Nuttawee , Mathew Esha , Bergkvist Magnus , Batt Carl A.
Published: October 2009

Owing to the increasing demand for miniaturized devices, and due to the limitations currently faced by conventional fabrication approaches, researchers aiming to construct nanometer‐scale devices have begun to explore novel bottom–up approaches lying at the interface of the inorganic and biological worlds. This article offers an overview of recent developments in bionanofabrication, as a unique approach for the manufacturing of inorganic nanostructures and materials with potential applications ranging from nanoelectronics, sensor devices to nanomedicine. First, two main areas of investigation are presented: (i) bionanofabrication via structural specificity of biomacromolecules and (ii) bionanofabrication via biochemical processes/catalytic activity in microorganisms (bacterial‐based bionanofabrication). This article will limit its discussion to bionanofabrication approaches that make use of DNA, proteins, and bacterial cells for the synthesis and organization of nanostructures and materials of (bio) technological relevance, such as metallic and semiconducting nanostructures (nanoparticles, nanowires, and nanotubes) and polymer‐based nanostructured materials. Finally, the advantages, limitations, and future directions of the bionanofabrication approach will be discussed.
Bioprocess Design, Computer‐Aided
Authors: Papavasileiou Victor , Siletti Charles , Koulouris Alexandros , Petrides Demetri
Published: October 2009

Design and evaluation of integrated biochemical processes is carried out at various levels of detail, depending on the stage of product and process development. Back‐of‐the envelope and preliminary evaluations are performed at the early stages of development; detailed design and evaluation are performed prior to the construction of a new facility. Both the preliminary and detailed design of integrated bioprocesses can be greatly facilitated by the use of appropriate computer aids, such as process simulators, discrete‐event simulators, finite capacity scheduling tools, and so on. The benefits of computer‐aided bioprocess design are illustrated using a typical monoclonal antibody production process. The process is described in detail, including thorough material balances. The batch execution of the process is visualized through Gantt charts and the concepts of cycle time analysis and reduction are presented. A methodology for sizing purified water supply systems and other utilities of batch manufacturing plants is described. Estimates of the capital and operating cost of such processes are provided with detailed breakdowns for the cost of materials and consumables are presented. The impact of multiple bioreactor trains, bioreactor scale, and product titer on the manufacturing cost is evaluated through sensitivity analysis. An introduction to Monte Carlo simulation is provided as a means for quantifying the impact of uncertainty and variability in process and market parameters. Finally, an introduction is provided to the design and operational challenges associated with multiproduct facilities.
Bioreactors, Mist
Authors: Weathers Pamela J. , Wyslouzil Barbara E.
Published: October 2009

Mist reactors offer unique capabilities to provide complete control of gases to in vitro cultures. This article covers the engineering fundamentals related to the design, fabrication, and operation of simple mist bioreactors for use in micropropagation and hairy root cultures, and includes lists of plant species successfully cultured in mists. Issues related to scale‐up are also discussed.
Bioreactors, Perfusion
Authors: Su Wei Wen
Published: October 2009

Perfusion culture entails continuous or semi‐continuous flow of a nutrient solution through a cell population while the cells are retained in the culture vessel. The main advantage of perfusion culture is its ability to achieve high cell density and allow convenient harvest of secreted products and/or removal of harmful extracellular metabolic byproducts. This oftentimes leads to improved volumetric productivity. In order to retain cells (and preferably viable cells) in a perfusion bioreactor, a key design element is the cell‐retention system. In this article, the current development of perfusion bioreactors for mammalian cell culture, with focus on the cell retention system, is reviewed.
Cell Growth and Protein Expression Kinetics
Authors: Kompala Dhinakar S.
Published: October 2009

Typical experimental data on the mammalian cell growth and protein expression kinetics in batch and continuous bioreactors are discussed with the focus on maximizing the protein production. Two strikingly different patterns of growth‐associated and inverse‐growth‐associated production kinetics observed in continuous bioreactors at steady state are discussed along with plausible mechanisms for explaining this difference such as the specific cell cycle phase‐dependent gene expression models. Unstructured kinetic models developed for kinetics of mammalian cell growth, substrate utilization, and protein expression are discussed to highlight the successes and failures of this modeling approach in simulating the dynamics of cell growth and production. Structured kinetic models, which are more detailed and hence capable of addressing the complex metabolism of mammalian cells, are introduced briefly along with their difficulty of estimating the values for the increasing number of model parameters.
Cell Immobilization: Engineering Aspects
Authors: Willaert Ronnie
Published: October 2009

The performance of immobilized cells is influenced by mass transport of substrates to the cells and of products from the cells to the bulk fluid, as well as the cell growth in the immobilization matrix. Both internal and external mass transfer limitations have to be considered in the design of immobilized cell systems. In this article, the various methods of measurement of the diffusion coefficient are reviewed. The influence of the presence and growth of living cells in the immobilization matrix on the diffusion coefficient is discussed. Internal diffusion in gel systems, microcapsules, and dense cell masses, that is biofilms, bioflocs, and mammalian cell aggregates is treated in detail, as well as internal mass transport by convection is considered. Finally, the mathematical modeling of reaction–diffusion systems of immobilized cells is discussed, with special attention to gel entrapment and microencapsulation.
Cell Products: Antibodies
Authors: Birch John R.
Published: October 2009

The applications of monoclonal antibodies are now widespread, as research tools, as
in vitro
diagnostic reagents and, increasingly, as
in vivo
diagnostic and therapeutic products. The number of antibody therapeutics on the market and in clinical trials has increased rapidly in recent years and global production has now reached tonnage quantities. Manufacturing technology is for the most part based on mammalian cell culture in fed‐batch suspension culture. Improvements in cell‐line construction and in media and feeds have led to dramatic improvements in productivity. Titers of grams per liter are now seen routinely and, increasingly, this is being achieved in media that are chemically defined and protein‐free. The requirement for very large quantities of antibody products also presents a challenge in terms of purification processes. Currently, purification is based on column chromatography, typically with a Protein‐A affinity step early in the process. In addition to optimizing processes for productivity, there is a growing awareness of the need to design cells and processes to deliver products with desired structural features.
Enhancement of Central Energy Metabolism, Microbial
Authors: Yokota Atsushi , Wada Masaru
Published: October 2009

Improving the productivity of useful metabolites is critically important for industrializing the fermentation process. For this to be achieved, rapid conversion of the fermentation substrate into the target metabolite through enhancing central metabolism seems rational. Since the discovery of “Pasteur effects” more than 100 years ago, scientific evidence has accumulated, especially in the past 50 years, that central metabolism is under the control of the energy status of cellsin vivoin such a way that catabolism is enhanced under energy‐deficient conditions. We investigated enhancement of fermentative production by boosting central metabolism through the manipulation of energy metabolism. We found that the introduction of defective F1Fo‐ATP synthase to impair oxidative phosphorylation is effective for enhancement of pyruvate production inEscherichia coliK‐12 (hereafter, we collectively define this mutation as the “atpmutation” since F1Fo‐ATP synthase is encoded by theatpoperon inE.coliK‐12). Clarification of the physiological alterations associated with theatpmutation revealed several interesting metabolic changes. Excellent producers of pyruvate and acetate have recently been engineered inE.coliK‐12, in which theatpmutation appears to contribute markedly to increase glucose consumption and metabolite production of the producers. Furthermore, theatpmutation was found to be effective for a gram‐positive industrially important bacterium,Corynebacterium glutamicum, in enhancing both glucose consumption and glutamic acid production. Elucidation of metabolic alterations in thisatpmutant revealed significant differences from those found in theE.coli atpmutant, suggesting a diversity of adaptive responses to energy deficiency in different bacterial species.
Conifers: Culture and Genetic Engineering
Authors: Bonga Jan M. , Von Aderkas Patrick , Klimaszewska Krystyna
Published: October 2009

Conifer biotechnology has advanced greatly in the last couple of decades. Even though much of the field is still experimental, improvements in somatic embryogenesis and cryopreservation protocols have resulted in the production of genetically improved planting stock for reforestation. This technology has been most effective for some of the spruce, pine, andLarixspecies as well as for Douglas fir. Other conifer species have been less responsive, and effective application procedures remain to be established. Genetic engineering is still largely confined to the experimental and field‐testing stage, but applications in the field of pathogen and pest resistance and some other features can be expected in the near future.
Biocatalysis: Database Tools
Authors: Wackett Lawrence P. , Ellis Lynda B.M.
Published: October 2009

Industrial biotechnology increasingly depends on the use of enzymes to carry out desired biotransformation reactions. The reactions have traditionally been used to produce specialty chemicals. Now, enzymic catalysis is being used to manufacture commodity chemicals and fuels. Thousands of enzymes are available commercially; millions are produced by microorganisms in nature. Applications of enzyme catalysis are based on using the best enzyme and optimizing metabolic pathways. Databases are crucial to this effort. Enzyme databases contain information on enzyme characteristics and substrate specificity. Gene sequence databases provide information crucial for cloning and expressing key enzymes. Metabolism databases reveal how enzymes interact in specific organisms to catalyze consecutive reactions. Microorganism databases provide information about the history and availability of individual strains. Chemical substance databases provide key compound information; solubility, reactivity, and biological activity. Commodity‐scale chemical substances that are substrates for industrial enzymes include sugars (glucose isomerase), sugar polymers (cellulase), nitriles (nitrile hydratase and nitrilase), proteins (rennin), and β‐lactam antibiotics (penicillin acylase). Databases will play a prominent role in synthetic biology, using biological tools to engineer novel enzymes and metabolic pathways for industrial biotechnology.
Dehydrogenase
Authors: Sánchez Antoni , Barrena Raquel
Published: October 2009

Dehydrogenase
is a general term describing a wide subgroup of oxidoreductases, enzymes that participate in reactions involving electron transfer. Because electron transfer implies the presence of an electron donor and an electron acceptor, and the chemical typology of these substances can be very different, the dehydrogenase class includes a large number of enzymes.

Dehydrogenases are produced by a large number of microorganisms and other living organisms. Numerous applications have been described for them, the most advanced being their use in chiral resolution after some immobilization procedure. Also, interest in using dehydrogenase activity to monitor the global aerobic activity in environmental biotechnology has grown in recent years. In this application, dehydrogenase activity is used to monitor the biodegradation process, as it is related to the metabolic reactions producing energy in the form of ATP through the oxidation of organic compounds. It has been successfully applied to the biological treatment of wastewater and solid wastes and soil bioremediation.

Specific dehydrogenase activity can be determined by a typical enzyme substrate–specific reaction. Nevertheless, values of overall dehydrogenase activity are also important because this value can often be related to the aerobic activity in ill‐defined (unsorted) media. In this case, two main substrates are typically used to accept electrons from dehydrogenase enzymes, triphenyl‐tetrazolium chloride (TTC) and 2‐(
p
‐iodophenyl)‐3(
p
‐nitrophenyl)‐5‐phenyl tetrazolium chloride (INT); the resulting reduced products are forms of red‐colored formazan (TPF and INTF, respectively).
Drying: Biological Materials
Authors: Law Chung Lim , Mujumdar Arun S.
Published: October 2009

New advancements in biotechnology has made many biotechnological products such as yeast, bacteria, vitamins, enzymes, proteins, carbohydrates, antibiotics, fungi, lysine, blood, plasma, realize in industry and commercial market. Most of these products appear in the form of liquid, suspension, or paste, which require refrigeration for storage. Refrigeration however limits the widespread application of the products mentioned above, as the operating costs and handling of frozen products is high and difficult. As such, dehydration and drying can be deployed to reduce the handling cost, while prolonging the shelf life, retaining the active ingredients activity, maintaining the cell survival and vitality, as well as its physical, textural, sensory, and optical properties. Biotechnological products are heat sensitive. Conventional drying methods for nonbiotechnological products such as hot air drying may damage and denature the product, destroy the cell and active ingredients, cause case hardening and browning. Over the years, freeze‐drying is the most common method used in the drying of some of the biotechnological products mentioned above. However, the operating cost and the drying time of freeze‐drying are comparatively high. As oil prices are skyrocketing and there is no sign that the price will ease in the near future, researchers and scientists have designed, tested, and improved various drying methods in order to improve drying efficiency and performance. This article discusses various conventional drying methods, which are common to the drying of biotechnological products, and describes various advanced drying technologies that give improvements and better performance with reference to drying strategy, drying medium, handling of drying materials, and mode of heat input. These include intermittent drying, pulse combustion drying, impinging stream drying, cyclic pressure vacuum drying, spray‐freeze‐drying, atmospheric freeze‐drying, vacuum fluidized bed drying, low‐pressure spray drying, superheated steam drying, heat pump drying, inert medium drying, supercritical fluid drying, sorption drying, spouted bed drying, jet spouted bed drying, vibrating fluidized bed drying, pulse fluidized bed drying, high electric field drying, and microwave drying. Recent research findings of these drying technologies are given as well.
Enzymatic Transglycosylation
Authors: Tramice Annabella , Andreotti Giuseppina , Giordano Assunta , Trincone Antonio
Published: October 2009

The most important functions of carbohydrates are structural roles and energy storage, but carbohydrate parts of glycoproteins and glycolipids are involved in biological functions mainly related to cell recognition events. Carbohydrates are also important molecules in the technological domain. A copious amount of information concerning the synthesis and transformation of complex saccharides in living organisms exists nowadays: the enzymes responsible for the synthesis of glycosidic linkage have been recognized as glycosyltransferases. Glycoside hydrolases (glycosidases) are different enzymes responsible for the hydrolysis of glycosidic linkages, but they can be efficiently used in synthesis. Indeed, at the present time, genetic engineering of glycosidases has emerged as a powerful tool for scientists, in the synthetic field, with the aim to set up chemically, efficient biocatalysts. In this contribution, the glycosyl transfer between oxygen nucleophiles will be analyzed from the chemical and the biotechnological points of view. Chemical machinery for hydrolysis and synthesis of the enzyme glycoside hydrolases and glycosyltransferases will be analyzed, including issues inherent to donors and acceptors and biocatalyst natural sources; in particular, discussing the modern genetic efforts to prepare tailored enzymes with high synthetic ability. Case studies for laboratory and industrial importance are analyzed as well.
Erythromycins
Authors: Minas Wolfgang
Published: October 2009

For well over 50 years the macrolide antibiotic erythromycin is in clinical use, and even today, macrolides hold a 20% share of the antibiotics market. The broad spectrum and the oral availability of macrolides have contributed to their success. The development of semisynthetic derivatives has greatly improved the clinical value of erythromycin and its derivatives. This article will provide an overview on erythromycin, its discovery, and biosynthesis, and on the development of semisynthetic derivatives. The macrolide's mode of action on the bacterial ribosome inhibiting the protein biosynthesis as well as the development of bacterial resistance is detailed. The clinical relevance of erythromycins, in particular of the latest developments, is emphasized.
Ethanol Fuel Production: Yeast Processes
Authors: Ingledew W.M.
Published: October 2009

The fuel alcohol industry has undertaken phenomenal growth since its rebirth in the 1980s. Since that time, it has developed with little industry‐wide appreciation of its size and strength, and the transformation of its science in order to lower production costs and to save energy and water. This short paper is designed to outline the steps of production in both wet milling and dry grind plants, provide a window on the new technologies that are proposed and utilized, demonstrate the size of the industry, the current energy balance in the process, the possibility of cellulose substrates augmenting starch‐based ethanol production, and provide a glimpse of the future of the industry.
Ethical Issues in Animal and Plant Cell Technology
Authors: Spier Raymond E.
Published: October 2009

Following a definition of ethics and the different ethical systems that are commonly referred to, the ways by which differences in ethical positions might be resolved are presented. These principles are then used in subsequent sections to examine in some detail the ethical issues that are raised when animal and plant cells are used in the context of biotechnology. While such subjects relating to enzymes and hormones are covered, emphasis is given to the viral products of animal cells and to the vaccines that are made to prevent disease. The use of animal cells to replace animals in test systems is also examined. Contemporary issues of regulation and biodefence bring together technology and ethics and show that we have the means for advances in these areas but only if we are mindful of the ethical issues and are prepared with arguments to meet possible objections. It is helpful in such deliberations to consider the panoply of capabilities in these areas as tools and to recognize that the regulation of tool use is dependent on the intentionality of the tool user as is the case for all the tools that are available with us.