bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Genes Underlying Human Inherited Disease
Authors: Stein Catherine M 
Published: April 2010

AbstractThe field of genetic epidemiology seeks to identify the genetic risk factors underlying human disease. First, one must assess whether the trait has an underlying genetic influence; this is done by estimating familial relative risk and conducting segregation analysis. In order to discover genes influencing human disease, both family‐ and population‐based studies are designed, and linkage and association methods are used to analyse the relationship between the trait(s) of interest and genetic markers. A variety of approaches to both linkage and association analysis exist, each having strengths and weaknesses for differing situations. In general, linkage analysis is more powerful for detecting rare genes, whereas association analysis is more powerful for detecting common allelic effects that might be weaker. In addition, when studying complex traits, other issues must be considered, including interactions with other genes and the environment, parent‐of‐origin effects, as well as the effect of structural variants.Key Concepts:Genetic epidemiologists design both family‐ and population‐based studies to find genes influencing disease risk.Before conducting a gene mapping study, one must first ascertain whether the trait is influenced by genetic effects.Linkage and association analysis are two complementary methods used to analyse the relationship between trait(s) and genetic markers.The approach used (linkage versus association) depends on the study design, and these approaches depend on the genetic parameters (rare versus common, large versus small effects).Other factors – gene–gene interaction, gene–environment interaction, existence of structural variants and parent‐of‐origin effects – further complicate the search for disease genes.
Studying Genomic Aberrations by Microarray Profiling
Authors: Walker Logan C , Waddell Nic 
Published: April 2010

AbstractInherited genetic variation between individuals is the main reason why we are different from one another. Genomic aberrations also play an important in the development of human diseases. An important tool for the study of these genetic changes is the microarray. Array technology has evolved over the years from traditional comparative genomic hybridization arrays to high‐resolution single nucleotide polymorphism (SNP) arrays, which can be used for SNP genotyping and the determination of copy number and loss of heterozygosity. These platforms will continue to play an important role in unravelling the complexity of diseases.Key concepts:Microarrays are a useful tool to assay changes in copy number, single nucleotide polymorphisms and loss of heterozygosity.There is inherited genetic diversity between individuals.Genomic aberrations play a key role in the development of many diseases.
Multiple Testing in Genetic Epidemiology
Authors: Han Buhm , Eskin Eleazar 
Published: April 2010

AbstractIf multiple statistical tests are performed simultaneously, we should take into account multiple testing to properly control the false positive rate. In association studies performing statistical tests for a large number of correlated markers, the traditional Sidák correction is overly conservative and the permutation test is inefficient. This article discusses recently proposed approaches for correcting for multiple testing in association studies. We first explain basic concepts of statistics such as thep‐value, false‐positive rate, correctedp‐value and family wise error rate. Then we discuss recently proposed methods in three categories: methods using multivariate normal distribution, methods calculating the effective number of tests and methods increasing the efficiency of permutation test. We compare the relative performance of these methods. Many of the methods are shown to be highly efficient and accurate compared to the traditional approaches and can readily be applied to the genome‐wide datasets.Key Concepts:In a statistical testing procedure performing multiple tests, multiple testing must be taken into account to properly control the false positive rate.In association studies, the traditional Sidák correction is overly conservative and the permutation test is inefficient.Recently proposed multiple testing correction methods are highly efficient and accurate and can be applied to the genome‐wide datasets.
Whole Genome Resequencing and 1000 Genomes Project
Authors: Chee‐Seng KU , En Yun Loy , Yudi Pawitan , Kee‐Seng Chia 
Published: April 2010

Abstract

The recent advances in sequencing technologies have enabled the whole human genome to be sequenced within weeks. To date, several human diploid genomes have been sequenced and the number of genomes being sequenced is expected to increase in the years to come. In fact, a 3‐year international collaborative project, the 1000 Genomes Project, was initiated in 2008 to sequence at least 1000 individual genomes from different populations around the world. The aim is to create the most detailed and comprehensive map of genetic variations in the human genome for future disease‐association studies and biomedical research. While waiting for this ambitious project to be completed, several whole genome sequencing studies have already provided some exciting results, where hundreds of thousands of new SNPs and short indels have been identified. In addition, these studies also address many important questions and issues in the experimental design and data analysis of whole genome sequencing.

Key concepts:

The arrival of next generation sequencing (NGS) and third generation sequencing technologies has empowered the sequencing of the whole human genome to be completed within weeks.

The first human whole genome sequencing (WGS) study using a next generation sequencer was completed in 2008, which marked the beginning of a new era in personalized genome sequencing.

To date, several WGS studies have been done using NGS technologies.

The NGS technologies are Roche
®
454 Life Science Genome Sequencer FLX (GS FLX), Illumina
®
Genome Analyzer (GA) and Applied Biosystems
®
(ABI) Supported Oligonucleotide Ligation Detection System (SOLiD).

The WGS studies have clearly demonstrated the feasibility of using all the NGS and third generation sequencing technologies to decode the DNA sequence of human genome efficiently and at an affordable price per genome.

In addition, these studies have also addressed many important questions and issues surrounding the experimental design and data analysis in whole genome sequencing.

The more significant finding from the WGS studies is that they have conclusively revealed the richness of genetic variations in the human genome. The genetic variations in the human genome are more abundant than previously expected.

Several thousands of structural variations are found in all the WGS studies, and the studies also identified hundreds of thousands of indels.

Personalized genome sequencing is able to provide full DNA sequences and identify the enormous number of genetic variations in the genome. However, personalized medicine aims to predict individual susceptibility risks to various diseases and responses to drug therapies using the genetic variation information.

To achieve personalized medicine, the first steps are to detect and validate all the genetic variations in the human genome in population‐based studies, and catalogue them properly in databases, so they can be used as the genetic markers for future disease association studies.
Acrylamide, Microbial Production by Nitrile Hydratase
Authors: Zheng Ren‐Chao , Zheng Yu‐Guo , Shen Yin‐Chu 
Published: April 2010

AbstractAcrylamide is one of the most important commodity chemicals widely used in coagulators, soil conditioners, adhensives, paints and petroleum recovering agents. The demand for acrylamide is readily growing yearly. Acrylamide is traditionally produced by chemical hydration of acrylonitrile employing sulfuric acid or copper salt as catalyst. Both of the processes were complicated and caused severe environmental pollution. The search for simpler and greener manufacture methods of acrylamide has never ceased. Discovery of nitrile hydratase and its application in nitrile hydration offers a novel method for the production of acrylamide. The worldwide development of biocatalytic acrylamide technology including the improvement of three generations of industrial strains as well as its current status is described. Microbial production of acrylamide affords both economic and technical advantages over the traditional chemical synthesis including high energy efficiency, high selectivity and purity. This is the first example of the introduction of an industrial bioconversion process for the manufacture of a commodity chemical and has been widely regarded as a milestone in the development history of industrial biotechnology.
Bacillus Megateriumand Other Bacilli: Industrial Applications
Authors: Bunk Boyke , Biedendieck Rebekka , Jahn Dieter , Vary Patricia S. 
Published: April 2010

AbstractStrains of the genusBacillusare Gram‐positive microorganisms. Many of them, such asBacillus subtilis, Bacillus licheniformis, Bacillus megaterium, Bacillus amyloliquefaciens, Brevibacillus brevis, andBacillus clausiioffer several advantages in industrial applications. They all have a very efficient protein secretion system, grow on several different and cheap carbon sources, lack endotoxins, and are nonpathogenic. Proteins produced from and with the bacilli are of great industrial importance. Next toB. subtilis,B. megateriumhas attracted the most attention in recent years. A toolbox for recombinant protein production, secretion, and purification has been developed that is based on various vectors with different origins of replication, selection markers, promoters, affinity tag sequences, and sequences for a signal peptide. The number of proteins recombinantly produced byB. megateriumhas increased rapidly. The genomes of twoB. megateriumstrains namely QM B1551, which naturally contains seven different plasmids but also has a plasmidless derivative, and DSM319, a naturally plasmidless strain, have now been completely sequenced. Systems biotechnology investigations using transcriptome, proteome, and metabolome analyses in combination with bioinformatics‐based modeling approaches have already started.
Baculovirus Expression Systems
Authors: Possee Robert D. , Hitchman Richard B. , King Linda A. 
Published: April 2010

AbstractBaculoviruses are insect‐specific pathogens, producing occlusion bodies containing enveloped virus particles which spread infection between insects. These occlusions or polyhedra are composed mainly of a 30 KDa virus‐encoded protein produced in the very late phase of virus replication. Polyhedrin protein is not required for virus replication in cell culture and so the gene coding region can be replaced with a foreign sequence of choice to generate a baculovirus expression vector. The inserted coding region is placed under the transcriptional control of the polyhedrin gene promoter by transfection of insect cells with circular or linear baculovirus DNA or via transposition in bacteria. The coding region can be modified to allow the addition of different secretion signal peptides or peptide tags or multiple gene promoters can be used for the expression of more than one protein. The baculovirus expression vector may also be modified by the removal of nonessential genes encoding products deleterious to recombinant protein production. High yields of protein are possible by scaling up insect cell cultures in serum‐free medium. Despite their specificity for insect cells, baculoviruses can also be use to transduce human cells, where recombinant genes can be expressed if placed under the control of mammalian‐specific gene promoters.
Bioenergetics of Microbial Growth
Authors: Heijnen Joseph J. , Kleerebezem Robbert 
Published: April 2010

AbstractIn this article we describe a methodology based on bioenergetic analysis of chemotrophic microbial growth systems that allows for a generalized system description. The main parameters can be estimated based on the identification of (i) the Gibbs energy supplying redox reaction and (ii) the carbon and nitrogen source for microbial growth. The calculated parameter values can be considered as a first approximation and allow for comparison with measured parameter values. Stoichiometric and kinetic parameter values that deviate strongly from the estimated values suggest that a highly specific microbial system is encountered. Herewith, the generalized method may serve as a reference framework for interpretation of stoichiometric and kinetic parameter values describing microbial growth processes.
Biominiaturization of Bioreactors
Authors: Hanson Michael A. , Rao Govind 
Published: April 2010

AbstractBioprocess development largely parallels the drug discovery process. Screening a large number of experimental conditions in the early stages, is required. As scales increase through the pilot to the manufacturing stage, process conditions get more stringent in terms of variation. Ideally, one would like the same quality of process information, independent of scale. Traditionally, early stage experiments to optimize growth media and cultivation parameters have been carried out in flasks and liter‐scale bioreactors. This has often resulted in slow development timelines due to a lack of information in the former and the low‐throughput nature of the latter. To circumvent these drawbacks in traditional technologies, much effort has been directed toward developing small‐scale culturing platforms with monitoring and control capabilities that would mimic production conditions. Such systems would enable more experiments to be carried out simultaneously without compromising the quality of information obtained. In this review, traditional as well as novel systems with monitoring and control capabilities are discussed. We have focused on their application in culture and, in many cases, comparison to larger scale systems. Many small‐scale systems have performances comparable to lab‐scale bioreactors. These advances should allow for much more efficient process development as well as impact other areas such as bioprospecting, where hitherto “uncultivable” species may now be grown by screening samples for growth under matrices of conditions that were previously impractical. Another area of impact will be to allow industry to more readily incorporate process analytical technologies.
Bioreactors: Airlift Reactors
Authors: Merchuk J.C. , Garcia Camacho F. 
Published: April 2010

AbstractALRs are popular in modern bioprocess research and development and, in many cases, they have found industrial uses. The distinctive characteristics of ALRs are conferred by the fluid dynamics of the liquid‐gas or liquid gas‐solid mixtures: holdup, liquid velocity, and mixing in the riser, gas separator, and downcomer. Only a correct understanding of the interconnection of these regions can make possible the scale‐up of a laboratory device, to pilot or industrial size. Several correlations are available in the literature for the prediction of the fluid dynamic characteristics of the reactor and of the mass and heat transfer coefficients, and a selection is presented in this review. Significant progress has been made in the application of modern computational tools to the simulation and design of ALRs. In parallel, innovative and sophisticated methods have been applied to obtain a deeper insight into the mechanisms of fluid motion and the flow patterns in the reactor. However, no single research group has managed to cover all the variables over a wide range. The engineer confronting scale‐up orde novodesign of an ALR must analyze the validity of the correlations and computation methods used for the calculations.
Nanomaterials Incorporated Bioelectronics
Authors: Alwarappan Subbiah , Li Chen‐Zhong 
Published: April 2010

AbstractBioelectronics can be defined as the functional integration of biological molecules together with electronic components. Bioelectronic systems combine the specific recognition properties of proteins or DNA with the mechanical and electrical properties of metallic or semiconducting solid‐state materials. A major aspect of a bioelectronic device is the generation or modulation of electrical current in an electronic circuit by means of molecular binding of the analyte of interest. In this article, we essentially give a brief introduction to bioelectronics followed by details about biosensors and their classification based on the molecular recognition component, methods of transduction, and materials employed. Following this, we have then briefly discussed the usefulness of a nanomaterials‐based system as transducer elements. In the next section, we summarize the efforts made by different researchers to develop a framework to support the biological machinery and its working principles for self‐assembly of molecular electronics. Next, we account for the usefulness of employing various carbon materials such as carbon nanotubes, carbon fibers, carbon onion, and the recently invented graphene as a substrate to design nanoscale biosensors for various applications. Finally, we have also provided information on artificial neural networks, their development and possible applications in medicine.
Quality by Design (QbD), Biopharmaceutical Manufacture
Authors: Shah Rakhi B. , Park Jun T. , Read Erik K. , Khan Mansoor A. , Brorson Kurt 
Published: April 2010

Abstract
The main concepts of the quality by design (QbD) initiative and applicability to biomanufacturing are described. QbD can lead to a future where product quality will be assured by flexible, science‐based approaches. QbD is an umbrella of related concepts and approaches that include quality target product profiles, risk assessments, design spaces, control strategies using process analytical technology, continuous process improvement and others. We will also discuss the regulatory structure supporting the QbD initiative, including the International Conference on Harmonization Quality documents ICH Q8(R1) (Pharmaceutical Development), ICH Q9 (Risk Assessments), ICH Q10 (Quality Systems) and FDA's Process Analytical Technology (PAT) Guidance. A case study is presented for applying QbD to a biopharmaceutical process, viral clearance by anion exchange chromatography. It is believed that QbD will lead to more flexible processes which are justified based on risk and science rather than on a solely empirical approach.
Industrial Biotransformation
Authors: Ghisalba Oreste , Meyer Hans‐Peter , Wohlgemuth Roland 
Published: April 2010

Abstract
The idea of using biological systems to create more efficient, selective, and environmentally friendlier processes for the conversion of raw materials into industrial products and the concept of a more sustainable use of the limited resources has been put into action long before the now worldwide accepted vision of sustainable development. This article discusses the principles of biotransformations with the advantages, application range, and technical aspects of biocatalysis. On the basis of the driving forces for R&D in industrial biocatalysis, the main screening strategies for biocatalysts are discussed. A short description of the history and companies, the chemical market, the manufacturing facilities, reactors and biocatalytic reactions is followed by selected examples of biocatalysis products manufactured at a large scale. The application spectrum of biocatalysis for industrial processes is much broader than generally perspected and the hope seems justified that the contribution of biotechnology in medium to large‐scale production processes can, in future, be significantly increased. The production of bulk chemicals using biotransformations is entering into a new era of global sustainability and is bound to make a significant contribution. With a truly sustainable global commitment and effort of real innovation in science, industry, and society in order to make it happen, the outlook is very optimistic. The resulting creation of value should not be viewed only from the short‐term cost perspective, but more in terms of long‐term knowledge building for a future bioeconomy.
Cell Detachment
Authors: Merten Otto‐Wilhelm 
Published: April 2010

AbstractCell detachment of adherently growing cells is a key operation in any cell culture laboratory as well as in animal cell technology in order to amplify cells for different purposes, which are the amplification for getting the cell number/mass for experimental and testing or necessary for production purposes. This monograph describes cell attachment in brief, trypsinization as reference method including a short review on the mechanisms of trypsin and the actual developments for replacing the use of trypsin which is an animal‐derived component by other enzyme‐based or nonenzymatic means to detach or dissociate cells. Specific issues concerning cell detachment at a large‐scale and under serum‐free conditions are also discussed.
Cell Separation, Centrifugation
Authors: Axelsson Hans 
Published: April 2010

AbstractA review of the different types of centrifuges used in industrial biotechnology is compiled, together with brief explanations of their function. The fluid and particle dynamics in the centrifuges is reviewed with some emphasis on the behavior of cells and other particles, and susceptibility to the shear forces acting on them. The classical mathematical models for the theoretical size, Σvalue, andKQvalue are characterized. The concept of separation efficiency, the deviation from ideal capacity, due to the simplicity of the mathematical model for the Σ value is defined. The considerations when selecting type and size of centrifuge for a given process are described, as well as the evaluation and enhancement of separability of the given process stream. The importance of small‐scale lab and pilot tests for a successful scale‐up is emphasized. Applications in harvesting of bacteria, yeasts, and mammalian cells are reviewed, as well as cell debris and inclusion body separations. Extraction—solvent and two‐phase aqueous—application examples are given. Finally, some plant and operation considerations such as plant design, CIP, SIP, containment, asepsis, and sterilization are briefly reviewed.