bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Genetics of Metastasis
Authors: Weber Georg F 
Published: April 2010

Abstract

Metastasis is the spread of cancer cells throughout the body. Although it is frequently the cause of death from malignant growths, it is the most poorly understood aspect of carcinogenesis. The underlying process of cancer cell dissemination is controlled by genetic programs in the tumour cells and in the host. The tumour cell‐intrinsic genetic programs of metastasis confer invasiveness and anchorage‐independence. The responsible genes are typically deregulated by aberrant expression or splicing. Organ preference of metastasis depends on more complex tumour–host interactions. Metastasis suppressor genes, when expressed, can negatively regulate tumour spread. The molecular genetics of metastasis has led to the development of diagnostic tests, based on gene expression profiles that help predict metastatic potential. Further, it has opened prospects for the targeting of key culprit genes in antimetastasis therapy.

Key Concepts:

Cancer invasiveness constitutes the breaking of tumour cells through tissue barriers and represents the earliest manifestation of metastasis.

The genetic basis of metastasis formation is the aberrant expression or splicing of stress response genes.

The biologic activity of metastasis‐mediating gene products is extensively regulated by posttranscriptional mechanisms.

Cancer metastasis is guided by two intrinsic characteristics of cancer cells, invasiveness and anchorage‐independent survival.

Cancer cell invasiveness is mediated by secreted proteases, homing receptors, cytokine ligands and associated signalling molecules.

The acquisition of invasiveness by tumour cells is accompanied by a characteristic, reversible remodelling, called the epithelial‐mesenchymal transition.

Cancers shed their tumour cells into the blood or lymph stream from the earliest stages of growth on; most cells die in the circulation.

Fully transformed cells can survive without anchorage for extended periods of time.

Genetic programs of metastasis encode consistent patterns of organ preference by individual malignancies.

Like other functions within cancer cells, the ability to metastasise is under positive and negative genetic control.
Molecular Genetics of Cardiac Arrhythmias
Authors: Wolf Cordula M , Berul Charles I 
Published: April 2010

Abstract

Knowledge derived from human genetics and from studies in animal models has led to the discovery of multiple molecular defects underlying inherited arrhythmias and cardiac conduction system diseases in structurally altered or normal hearts.
Minor disturbances at the molecular and cellular levels can initiate severe rhythm abnormalities. Some congenital heart diseases and cardiomyopathies carry a higher risk for conduction disturbances or arrhythmias. In the structurally normal heart, inherited cardiac arrhythmias or conduction system disease are most often primary electrical diseases. The underlying molecular defect in those disorders, also termed ion channelopathies, typically involves genes that encode ion channels, responsible for maintaining intracellular and extracellular electrolyte balance.
Advances in molecular biology and genetics facilitate the identification of factors that may predispose an individual with or without structural heart disease to arrhythmias or sudden death. Taking those discoveries into clinical practice improves risk stratification and allows potential identification of new therapeutic targets.

Key Concepts:

Sudden unexpected cardiac death in the pediatric population is a devastating event with an incidence of approximately 1–6 in 100 000 per year and in some cases is the first presentation of a previously undiagnosed disorder.

Inherited arrhythmias and cardiac conduction system disease frequently occur in pediatric patients with congenital heart disease but can also be associated with a structurally normal heart.

Mutations in genes encoding for cytoskeletal proteins, sarcomeric proteins and ion channels are responsible for the majority of inherited arrhythmias associated with the structurally normal or abnormal heart.

Identifying the molecular basis of congenital arrhythmias optimises patient screening, risk stratification and allows genotype‐directed therapies of patients at risk for sudden cardiac death.
Aeration, Mixing, and Hydrodynamics, Animal Cell Bioreactors
Authors: Godoy‐Silva Ruben , Berdugo Claudia , Chalmers Jeffrey J. 
Published: April 2010

AbstractMixing and aeration are normally used to provide a homogeneous, suitable environment for cells in a bioreactor. In spite of the large cumulative experience in the use of bioreactors in the biotechnology industry, there are still challenges when scaling‐up animal cell cultures. Remarkable advances have been achieved over the last two decades in designing and applying mixing and aeration strategies, as well as understanding the effects of hydrodynamic forces on cell cultures.This section reviews the basic concepts and current practices for mixing and aeration in bioreactors, with focus on stirred tank bioreactors (STR), as most of the processes for recombinant proteins, antibodies, and vaccines involve the use of STR. Current methods of oxygen supply in STR include surface aeration and gas sparging, although the use of perfluorocarbons, oxygen carriers and membranes has been investigated. Sparger design and the role of CO2accumulation and removal are discussed. Also, a summary of the main aspects involved in mixing is presented, including tank characteristics, impeller geometry, and power drawn. Finally, this review explores several different approaches that have been taken in order to unveil the response of animal cells to the hydrodynamic forces generated inside bioprocessing devices.
Agricultural Biotechnology, Food Safety, Risk, Consent, and Ethics
Authors: Thompson Paul B. , Hannah William 
Published: April 2010

Abstract
The ethical rationale for acceptable food safety risks can be interpreted according to two competing paradigms. The expected value paradigm stipulates that risks are functions of the harm associated with an adverse outcome accruing as a result of food consumption and the probability of that outcome. Although quantification of expected values for food safety presents challenges, the standard for acceptable risk is conceptualized as optimization of expected values. In present practice, optima for food safety risks are generally characterized as de minimus criteria. The alternative paradigm presumes that longstanding patterns of social food regimes constitute background practices not subject to moral judgment or risk assessment. Deviations from such patterns are understood as risky, and become acceptable only under the condition of informed consent for risk‐bearers. While in many cases, both paradigms converge on a common policy, for foods derived from genetic engineering, they have diverged.
Animal Cell Culture Media
Authors: Vijayasankaran Natarajan , Li Jincai , Shawley Robert , Chen Aaron , Shiratori Masaru , Gawlitzek Martin , Li Feng , Kiss Robert , Amanullah Ashraf 
Published: April 2010

AbstractFed‐batch cell culture processes are the standard platform technology for the synthesis of high value biopharmaceutical proteins. Recent advances in cell line development and in the optimization of culture medium have enabled the operation of fed‐batch processes at significantly higher volumetric productivities than previously realized. While a robust basal medium is essential to ensure high productivity, a well‐developed feed medium coupled with an appropriate feeding strategy are essential for sustaining it over the course of the culture duration. Furthermore, optimization of cell culture medium needs to be cognizant of specific goals for its use. Different optimization strategies are adapted for developing platform media applicable for multiple cell lines and customized media developed for specific cell lines. While volumetric productivity continues to be an important parameter for cell culture medium optimization, the developed medium should also be robust during implementation in biopharmaceutical manufacturing facilities. The developed medium should be easy to prepare and have a long shelf life to ensure ease of process implementation in multiple commercial and clinical‐scale manufacturing sites. Due care should be taken to ensure that optimization of media does not lead to unacceptable alterations in the quality of the expressed protein. This article will address all these aspects that ensure the efficient optimization and implementation of animal cell culture media.
Animal Cells, Hybridomas, Human Antibody Production
Authors: Warren James C. , Subramanian Shyamsundar 
Published: April 2010

AbstractCellular response to perturbations in the microenvironment manifests as a surge of physiological changes that have great impact on cellular metabolism and propagation. In bioprocess systems, mammalian cells engineered for the production of monoclonal antibodies or therapeutic proteins are sensitive to fluctuations in the culture environment. These fluctuations often directly translate to changes in maximum attainable cell concentration and/or specific protein productivity. In conjunction with feeding strategy optimization, the ability to understand and optimize the physical environment of animal culture systems is key to achieving a process that delivers consistent production of high titer batches. In this article we have reviewed comprehensively two critical physical culture parameters: osmolality and temperature, for their effects on general cellular physiology as well as their impacts on overall culture performance in bioprocess systems. Extreme levels of osmolality lead to volume‐regulatory responses, cytoskeletal reorganization, and trigger distinct cellular signaling pathways. Cellular responses to hypothermic conditions include reduced metabolic and growth rates, reduction of apoptosis frequency, and a cold‐shock response which involves the increased synthesis of several proteins. Exposure of cells to hyperosmotic conditions and/or subphysiological temperature (32–35°C) has been shown to enhance specific protein productivity in bioprocess systems. As live viruses are also commonly produced in industrial cell culture systems for vaccine processes, we have extended the scope of this article to include the effects of fluctuations in culture osmolality and temperature on the production of live viruses.
Animal Cell Types, Hybridoma Cells
Authors: Heilmann K. , Micheel B. 
Published: April 2010

AbstractThe hybridoma technology developed from Köhler and Milstein over 20 years ago is till today the scientific standard in generating monoclonal antibodies and demonstrates a hallmark in biotechnology and biomedicine. This basic method and all arising technologies opened up a new field of experimental designs and innovative results to understand and clarify courses in diseases. The possible application of antibodies in research leads to well‐defined characterizations of cell types, cell‐cell and cell‐matrix interactions and correlation of signaling cascades. These perspectives indicate a continuous requirement and therefore a huge global demand for antibody molecules, related detection markers, and biomedical tools. In the course of this development, a multitude of new techniques is necessary and will be designed in future to simplify the generation of human therapeutic antibodies which seem to be a highly effective tool in the treatment of malignant or autoimmune diseases.
Antibiotics: Biosynthesis, Generation of Novel Compounds
Authors: Weber Tilmann 
Published: April 2010

Abstract
Many antibiotics and other bioactive molecules originate from biological sources, mainly bacteria and fungi. In this article, the biosynthetic principles of the three most important classes of antibiotics are discussed and examples of the biotechnological potential of pathway engineering are presented.
Polyketides, among them medically important antibacterial drugs like tetracycline or erythromycin, are assembled from basic acyl‐CoA building blocks by a mechanism that is closely related to fatty acid synthesis. Another important group of antibiotics are modified peptides like penicillin or vancomycin which are synthesized by complex modular megaenzymes. These nonribosomal peptide synthetases use proteinogenic as well as nonproteinogenic amino acids as substrates. In addition some other peptide antibiotics, like the lantibiotic nisin which is widely used as a food additive, are synthesized by the cellular ribosomal protein biosynthesis machinery and subsequently modified by specific enzymes. Aminoglycoside antibiotics like streptomycin are assembled from complex sugar or sugar‐like molecules which are specifically synthesized during secondary metabolite production.
The elucidation of the molecular machinery of antibiotic biosynthesis enabled technologies that can be used to optimize the secondary metabolites by genetic engineering. In this article, some strategies are highlighted which allow the modification of secondary metabolites in ways that were hard to achieve using only synthetic chemistry approaches.
Protein Aggregation and Precipitation, Measurement and Control
Authors: Schein Catherine H. 
Published: April 2010

AbstractAggregation is both a blessing and a curse to the biochemist seeking to purify and use recombinant proteins. Reversible aggregation/precipitation induced by agents such as polyethylene glycol and salts can be used to purify proteins. However, proteins often undergo uncontrolled and irreversible aggregation that prevents regeneration of activity. This article summarizes methods to measure aggregation and to determine the intrinsic solubility of proteins. Much of this research has been driven by the need to formulate medically useful proteins so that they remain soluble, and to develop treatments for diseases that involve protein aggregation, such as Alzheimer's and other neurodegenerative diseases.Theoretical treatments of the effects of co‐solvents on the solubility of proteins, including using empirical data to deriveatomic solvation parameters(ASP), may be useful for some applications. Mathematical models and protein phase diagrams have been developed for common precipitants, although there is no common basis for theira prioriuse with a given protein. There are also some general rules for designing mutants with reduced aggregation tendencies. To this end, computational methods may be used to estimate the solvent exposure of residues in 3D‐structures, predict surface patches that may dictate protein–protein interactions, and to model the 3D structure.
Biosensors, Aptamers (Aptasensors)
Authors: Bini Alessandra , Mascini Marco , Turner Anthony P.F. 
Published: April 2010

AbstractAptamers are single‐stranded DNA or RNA ligands which can be selected for different targets, starting from a huge library of molecules containing randomly created sequences. Aptamers have been selected to bind very different targets, from proteins to small organic dyes. The different fields of analytical chemistry, when dealing with systems based on biomolecular interactions, are still dominated by immunoassays, but detailed analytical studies are now demonstrating that some of the limitations of these conventional assays can be circumvented by alternative recognition reagents such as aptamers. Aptamers have been extensively used in many analytical applications such as chromatography, electrophoresis, mass spectrometry, molecular beacons, sensors and biosensors. This chapter focuses on the particular case of biosensors employing aptamers as new biorecognition elements, which are known as “aptasensors”. This chapter describes the specific features of aptamers and reports on their employment for the development of aptasensors, especially as applied to the detection of clinically‐relevant proteins for diagnostic assays. However, the large variety of aptamers which have been selected to bind low molecular weight molecules leads to the possible use of these oligonucleotides in a wider range of applications such as assays for the analysis of environmental and food samples, as well as detection terrorist threat agents that are biological.
Biocatalysis, Cofactor Regeneration
Authors: Zhang Jie , Xu Jian‐He 
Published: April 2010

AbstractBiocatalysis and biotransformation could provide valuable chemicals for the industry via eco‐friendly processes. Among the biocatalysts, except cofactor‐independent hydrolases, the cofactor‐dependent enzymes are the second class to perform the bioreactions. However, the complexity and high costs of cofactors limit the application of such enzymes in a wider field. Thus, it is necessary to regenerate cofactorsin situ. Regeneration of cofactors, such as NADH, NADPH, ATP, sugar nucleotides, 3′‐phosphoadenosine‐5′‐phosphosulfate (PAPS), have been studied extensively in the past 30 years. Different methodologies for cofactor regeneration including chemical, electrochemical, photochemical, enzymatic and permeabilized cells methods have been developed. These methods are reviewed in this chapter, along with some successful examples in industrial application.
Biofuel Cells, Performance Characterization
Authors: Watanabe Kazuya 
Published: April 2010

Abstract
Biofuel cells are devices for generating electricity from chemical fuels (such as hydrogen and organic compounds) using biological catalysts (i.e. enzymes and/or living microbes) for electrode reactions. They could be divided into two categories based on types of catalysts; namely, enzyme fuel cells (EFCs), and microbial fuel cells (MFCs). In this article, procedures for evaluating biofuel cells are described, since appropriate evaluation is fundamental to developing efficient processes and also for comparing biofuel cells developed in different laboratories. Special focus is on the evaluation of MFCs, since MFCs need more diverse criteria than EFCs for performance evaluation; however, EFC evaluation is also possible using the procedures and parameters described in the article.
Bioprinting, Inkjet Deposition
Authors: Saunders Rachel , Derby Brian 
Published: April 2010

AbstractInkjet printing is a versatile deposition and patterning technology that can be used for the controlled placement of picoliter volumes of fluids. The mechanisms of drop generation are reviewed and the fluid requirements for successful printing discussed. Inkjet printing has been successfully used for the deposition of biomaterials, proteins, and living cells. The response of these materials to the printing process is discussed. A number of practical applications are discussed, including biosensors, experimental cell biology, and tissue engineering or regenerative medicine.
Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics of Protein Therapeutics
Authors: Vaddady Pavan K. , Meibohm Bernd 
Published: April 2010

AbstractThere is a growing interest in the role of proteins as therapeutic agents. Protein drugs often have specific characteristics that affect their pharmacokinetics (PK) and/or pharmacodynamics (PD) and make them distinctively different from small molecule drugs. Understanding the processes involved in the disposition of a protein molecule following administration such as its absorption, distribution, and elimination gives insights for developing and designing optimum dosage regimens as well as dosage forms. Similarly, the relationship between the drug concentration and associated biochemical and physiological processes related to the drug's mechanism of action is essential to discern its efficacy and toxicity potential. This article focuses on the relevance of PK and PD affecting the efficacy, safety, and use of protein therapeutics. It emphasizes on the available administration routes, explores different ways a protein molecule takes to reach its target tissue, and discusses the most relevant mechanisms by which protein therapeutics are eliminated from the body. It furthermore discusses a variety of PK/PD modeling approaches most commonly used for the characterization of the dose‐exposure–response relationship of biologics.
Single‐Use (
SU
) Systems
Authors: Maigetter Robert Z. , Piombino Tom , Wood Christian , Gervais Tom , Thomasin Claudio , Shingle Bryan , Wareheim Dave A. , Clark David 
Published: April 2010

Abstract
This chapter will focus on the opportunities for SU systems and their acceptance into bioprocess facilities building new or retrofitting with 100% SU. The first section of the chapter will examine the more traditional stainless steel bioreactors and tanks, how they have been replaced by SU, and how existing and new facilities could incorporate both. Subsequent sections will address cell culture, purification, fill and finish, media and buffer, and end with a presentation of costs.
Biophotoreceptor Arrays
Authors: Knopf George K. , Wang Wei Wei 
Published: April 2010

AbstractBiophotoreceptor arrays are hybrid electronic devices that utilize spectrally sensitive neuronal cells and biomolecules as the primary photon‐detecting element in a distributed network of light sensors. The patterned microelectrode arrays that interface with the biological material are constructed from readily available silicon‐based circuitry or, more recently, electrodes imprinted on flexible polymer substrates. From an engineer's perspective, these biological materials present new design opportunities for developing imaging systems that more closely emulate the signal detection and information processing structures found in nature. Several important attributes of natural vision include highly sensitive light receptors based on molecular phototransduction, a nonregular distribution of sensing elements on the imaging surface, and nonplanar image formation in the eye. The primate retina is one illustrative example of how phototransduction and neuronal interactions can lead to efficient imaging of dynamic three‐dimensional environments. The extraction and deposition of nerve cells and molecular proteins on microelectrode array platforms provide researchers with a means to observe the behavior of these distributed sensing systems. Organic and flexible polymer electronics represent a new technology that permit the creation of nonrigid photoreceptor arrays which replicate the curved imaging surfaces of single aperture and apposition compound eyes. A simple motion detection system is presented as an illustration of how photosensitive biomaterials and flexible printed electronics provide an alternative paradigm for developing new types of imaging systems. An important area where biomedical researchers can exploit engineered biophotoreceptor arrays is the fabrication of biocompatible artificial retinas and prosthetic devices for patients with severe visual impairment.
Biopolyester Particles: Preparation and Applications
Authors: Rasiah I.A. , Parlane N. , Grage K. , Palanisamy R. , Jahns A.C. , Atwood J.A. , Rehm B. H.A. 
Published: April 2010

AbstractOver the past few decades, there has been a growing awareness of the potential uses of biodegradable polymers in biotechnology and medicine. In particular, micro‐ and nano‐sized particles which are made from natural resources, exhibiting biodegradability, biocompatibility, and low toxicity have been the subject of intense research and development in many areas. Apart from their beneficial material properties, these particles allow variations in structure and composition to be designed, thereby tailoring them for specific applications. This review presents a broad overview of the main categories of biopolyester particles described in the literature, and putting emphasis on the composition and preparation of each group, followed by the wide variety of applications and potential uses described to date.