bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene transfer to the liver
Authors: Ponder Katherine Parker
Published: July 2005

The liver is an important organ for gene therapy. There are a large number of genes that are expressed in the liver whose deficiency results in a genetic disorder that might be treated by expressing the deficient protein in the liver. In addition, hepatitis B and C are very common, and might be treated with vectors that express small interfering RNAs that downregulate viral gene expression. Hepatocytes are readily accessible to viral or plasmid vectors that are injected systemically owing to the fenestrations in the blood vessels in the liver, which makes in vivo delivery feasible. Gene therapy has had considerable success in the liver in animal models. Both retroviral and AAV vectors have been delivered to animals with no obvious toxicity and have resulted in long‐term expression in both small‐ and large‐animal models. Although adenoviral vectors have achieved very high levels of expression in rodents, they have evoked substantial inflammation, and have not resulted in stable expression in most large‐animal studies. Plasmid vectors have been effective, although efficient delivery to the hepatocyte remains a problem. One or more of these gene therapy approaches will likely translate into an effective therapy for patients in the near future.
Hierarchical, ordered mapped large insert clone shotgun sequencing
Authors: Roe Bruce A.
Published: July 2005

DNA sequencing has become a powerful tool to deepen our understanding of the genetic basis for living systems. Although the basic principles of the Sanger dideoxynucleotide chain extension approach have changed little since it was developed over 30 years ago, the detailed methodology and technology to implement it have resulted in an approximate doubling of the amount of DNA sequence data annually since then. From its initial labor‐intensive implementation by which only fairly short DNA segments could be sequenced, present day DNA sequencing now entails a shotgun‐based approach that can yield the complete sequence of target regions that are in the megabase pair range. However, when the shotgun approach is coupled with a hierarchical approach in which megabase to gigabase genomes are dissected into ordered maps of large insert clones that are tractable to highly automated shotgun sequencing, that the complete, highly accurate reference genomes for several organisms, including humans, have been determined. But science and technology do not stand still, as new and exciting approaches to obtain DNA sequence data hundreds to thousands of times faster and less expensive than presently available loom on the horizon, giving us the ability to gain an even deeper understanding of the genomes of hundreds of diverse organisms, from animals to plants, as well as the readily available sequence of our individual hereditary material and the prediction of our individual predisposition to genetic‐based diseases and physical traits.
Genome mapping overview
Authors: Warren Wesley C. , Lovett Michael
Published: July 2005

Genome mapping has had a central and fundamental influence on both genomic sequencing and positional cloning over the past 20 years. The technologies underlying this field fall into three broad categories: (1) true physical maps based upon ordered genomic clones or the cytogenetic map; (2) inferred physical maps based upon a statistical analysis of map order, for example, radiation hybrid (RH) maps; (3) genetic maps that deliver a relative order of polymorphic markers based upon statistical analysis of meiotic recombination crossovers. All three types of reference mapping resources have caveats and limitations. The first is the assumption that the reference map truly reflects the underlying genome. Genomic duplications, inversions, and other complex rearrangements (which may vary between individuals) can complicate the interpretation of these maps. Sex‐specific differences can complicate genetic maps. Any type of statistically based map (whether RH or genetic linkage) should be carefully scrutinized for the likely odds of marker order. There are also gaps in many of the available maps and these can also present problems. Here we present a brief overview of the various genome mapping methods.
Linkage mapping
Authors: Samuels Mark E. , Dubé Marie‐Pierre
Published: July 2005

Linkage mapping refers to the specification of a particular chromosomal segment or segments within the genome that carry a causal DNA variant or mutation leading to a biological phenotype of interest. The appropriate chromosomal segment is determined through the use of anonymous polymorphic DNA markers as tags in different individuals who share the phenotype. Statistical analysis of data is usually critical in the determination. For whole‐genome linkage analysis, the most commonly used polymorphic markers are short tandem repeats, known as microsatellites or STRs. The experimental use of these markers has many subtleties and pitfalls, which are reviewed. Successful linkage mapping for a phenotypic trait is followed by the process of positional cloning, whereby the true underlying genetic variant is discovered. The final step from anonymous chromosomal segment to sequence variant detection can be relatively straightforward or highly demanding, depending on the complexity of the phenotype, the severity of the mutation in affecting gene function, and the extent to which carriers of the mutation are predisposed to the phenotype.
Microarray comparative genome hybridization
Authors: Holt Robert A. , Krzywinski Martin
Published: July 2005

Microarray comparative genome hybridization (maCGH) is a highly parallel assay for detecting DNA copy number changes. The method has been used to detect copy number alterations associated with cancer, congenital anomalies, and developmental disorders. CGH extends the diagnostic power of G‐banding and FISH imaging, but is limited to the detection of only those aberrations that are accompanied by changes in the copy number of genomic segments. Over the past decade, different CGH formats have been explored (chromosome spreads, clone microarrays, and oligonucleotide microarrays) in efforts to increase both resolution and sensitivity, and thereby improve the utility of the approach for both research and clinical applications.
The
H
appy mapping approach
Authors: Galibert Francis
Published: July 2005

“Happy mapping” is an in vitro genome mapping method for type 1 and 2 markers that offers several advantages over the RH method. However, it is highly dependent on a whole‐genome amplification step that till now has been difficult to realize given the very small amount of starting DNA. In this article, advantages and possible future developments are discussed in light of the difficulties inherent in the method.
The distribution of genes in human genome
Authors: Bernardi Giorgio
Published: July 2005

The human genome is a mosaic of isochores, long (>300 kb) DNA regions, each one of which is characterized by a low compositional heterogeneity. Isochores belong, however, to a small number of families that cover a very broad GC range (GC is the molar percentage of guanine + cytosine in DNA). An isochore pattern is very widespread in eukaryotes. This pattern (the “genome phenotype”) is stable over geological times, but is different in different vertebrate and plant classes. In all vertebrates, there are good correlations between the GC levels of coding and contiguous noncoding sequences, as well as among the GC levels of different codon positions. Such correlations amount to a “genomic code”.

Gene distribution is bimodal in vertebrates, gene density being very high in the small “genome core” (corresponding in the human genome to the GC‐richest isochore families H2 + H3) and very low in the vast “genome desert” (formed by the other isochore families L1, L2, and H1). The gene distribution of vertebrates is correlated with important structural, functional, and evolutionary features.
Genome archaeology
Authors: Aparicio Samuel
Published: July 2005

The generation of complete genome sequences for a number of animals has enabled the development of a new archaeology that has allowed us to study the evolution of both gene content and function of diverse species. These studies have revealed surprising new features of the structure of genomes and their evolution as well as uncovered new genetic elements along with insights into how they evolved and their role in biological mechanisms.
Functional analysis of genes
Authors: Woychik Rick , Bult Carol
Published: July 2005

Studying the function of genes is a multidimensional process that involves many organisms and a large variety of experimental approaches. No single organism is best suited for all experiments, and no single experimental strategy is appropriate for all genes. In the end, integrated electronic resources with data collected from all genes in yeast, flies, worms, mice, zebra fish, rats, and human will best serve the needs of the biomedical research community to study gene function.
The rat as a model physiological system
Authors: Gauguier Dominique
Published: July 2005

The laboratory rat is a major experimental animal in all fields of biomedical research. It provides a broad range of models for accurately characterizing the effects of naturally occurring gene variants on the regulation of complex phenotypes underlying the pathogenesis of common and prevalent human genetic disorders. The completion of the rat genome sequence and progress in comparative genomics provide key resources that facilitate the characterization of disease genes at quantitative trait loci (QTLs). Genetic, physiological, and functional genomics investigations in existing inbred rat strains and emerging congenic and consomic panels are now contributing, in combination with studies in mouse models, to the functional annotation of mammalian genomes, and the identification of candidate genes for human multifactorial diseases.
The Fugu and
Z
ebrafish genomes
Authors: Elgar Greg
Published: July 2005

Ray‐finned fish comprise the most abundant class of vertebrates with over 20 000 different species covering almost every aquatic habitat on Earth. They represent a tremendously diverse evolutionary range, having evolved from a common ancestor as far back as 450 million years ago, at around the same time they split from the lobe‐finned lineage that led to the tetrapods, including amphibians, birds, reptiles, and mammals. While there is a considerable amount of genomic and genetic data for a number of fish species, two have been particularly well studied at the genome level, the zebrafish,
Danio rerio
, and the Pufferfish,

Fugu rubripes

(Fugu). Interestingly, these two fish are only distantly related, each having its own unique characteristics, and this has resulted in them being exploited in quite different ways by molecular biologists.
The staphylococci
Authors: Gill Steven R.
Published: July 2005

The staphylococci are opportunistic pathogens and a major cause of hospital‐ and community‐acquired infections ranging in severity from minor skin infections to widespread life‐threatening infections. The occurrence of highly virulent community‐acquiredStaphylococcus aureus(CASA) and continued progression of resistance to multiple antimicrobials, including vancomycin, marks a re‐emergence of the staphylococci as serious health care threat. Multiple genomes of the two major staphylococcal pathogens,S. aureusandStaphylococcus epidermidis, have been sequenced (genomes of sevenS. aureusisolates and twoS. epidermidisisolates). Comparative analysis of these genomes has shown that they are syntenic along their length and share a core set of genes with roles in metabolism and general housekeeping functions. Nonsyntenic regions contain species‐specific genes and pathogenicity genomic islands, including bacteriophages, which are the primary source of variations in pathogenicity and resistance. Overall differences in pathogenicity between the two species can be attributed to genome islands inS. aureus, which encode exotoxins, leukocidins, and leukotoxins not found inS. epidermidis. Gene transfer among staphylococci and with other low GC gram‐positive bacteria has contributed to the evolution of resistance and virulence and is likely playing a role in the emergence of increasingly virulent members of the staphylococcal family.
Spirochete genomes
Authors: Weinstock George
Published: July 2005

Spirochetes are a group of bacteria with a common threadlike morphology. Nevertheless, these organisms show great genomic diversity, ranging in size from 1 to over 4 Mb and in chromosome structure from the simple bacterial circular chromosome to complex collections of linear and circular chromosomes. The gene content of pathogenic spirochetes often shows few of the virulence factors found in the more extensively studied Proteobacteria or gram‐positive bacteria. This may reflect the significant evolutionary distance from spirochetes to these other microbes as well as different strategies of infection.
SNPsand human history
Authors: Wall Jeffrey D.
Published: July 2005

Evolutionary geneticists have shown great interest in using patterns of single‐nucleotide polymorphism (SNP) variation to make inferences about models of human evolution. Although there is a large amount of variability in the patterns across regions, a couple of trends have emerged: overall levels of variability are low, indicative of a small historical effective population size, and there are systematic differences in the patterns of SNP variation both across different regions of the genome and across human populations. The connections between these broad patterns and models of human evolution are unclear, in part because of the difficulty in quantifying the verbal models of physical anthropology. This will change soon with the development of new analytical methods and the gathering of more human SNP data.
The role of nonsense‐mediated decay in physiological and pathological processes
Authors: Holbrook Jill A. , Neu‐Yilik Gabriele , Hentze Matthias W. , Kulozik Andreas E.
Published: July 2005

In eukaryotes, a conserved surveillance pathway known as nonsense‐mediated decay (NMD) regulates the abundance of mRNAs containing premature termination codons (PTCs), defined as in‐frame stop codons located upstream of the physiological (i.e., normal) stop codon. PTCs often arise as the result of mutations but can also occur in normal transcripts as a result of physiological processes. NMD appears to have evolved as a means of both controlling expression of physiological (i.e., nonmutated) transcripts containing PTCs and of limiting production of protein from abnormal PTC‐containing transcripts. The mechanism of NMD is described and its roles in normal cellular function and in some forms of genetic disease are discussed.
EST
clustering: a short tutorial
Authors: Hide Winston A.
Published: July 2005

This article provides a simple introductory framework for understanding the concepts and underlying reasoning for expressed sequence tag (EST) clustering and subsequent transcript reconstruction. It represents an overview of only the very well established methods and acts as a guide to the researcher to relevant sources for further understanding.
Microarrays: an overview
Authors: Hoheisel Jörg D.
Published: July 2005

Microarrays have become a tool that is synonymous to modern molecular biology. From beginnings that were aimed at the high‐throughput sequencing of the human genome, a wide variety of different technology platforms emerged, on which an even larger number of assay formats are performed. Currently, the technology is in a state of transition. The initial developmental phase is finished, with part of the technology established to a degree that processes are on the brink of routine application. Simultaneously, however, new applications and technical advances emerge continuously, which require further development and evaluation, also moving into fields other than the analysis of nucleic acids.
Genomic analysis of host pathogen interactions
Authors: Kellam Paul , Gale Catherine V.
Published: July 2005

Infection of multicellular organisms by microbes occurs throughout, and can shape, the evolutionary history of both the host and the pathogen. Following exposure, transcriptional remodeling of infected cells and cells of the innate and adaptive arms of the immune system results in both disease symptoms and eventually in pathogen clearance. Failure of this integrated system results in host death. More sophisticated microbes are able to dramatically blunt cellular defense mechanisms, and in some cases, reprogram cellular gene networks to allow persistence within the host. This is sometimes a beneficial, symbiotic relationship, but often results in life‐long host infection, occasionally with delayed pathogenesis. Transcriptional profiling studies have started to uncover the coordinated host response to microbial encounter that should ultimately produce a greater understanding of microbial pathogenesis.
Bacterial genome organization: comparative expression profiling, operons, regulons, and beyond
Authors: Peterson Scott N.
Published: July 2005

The sequencing of complete microbial genomes has provided a molecular basis for the diversity of bacterial species. Bacterial gene expression in response to environmental stimuli may be equally diverse and raises the question as to how well what we learn about gene expression in one species translates to another. A problem common to all scientists performing global gene expression lies in determining the significance of gene expression changes as they relate to the functional requirements of the encoded proteins in the biological process under investigation. Four recent studies are presented that highlight some of the issues that confound direct interpretation of gene expression data, including operon structure, functional redundancy of proteins, and the occurrence of nonorthologous genes in bacteria. The concept of comparative expression profiling (CEP) is introduced and discussed in the context of the experimental results observed.
Tissue microarrays
Authors: Simon Ronald , Mirlacher Martina , Sauter Guido
Published: July 2005

Tissue microarrays (TMAs) allow for simultaneous analysis of thousands of well‐characterized tissues and have, therefore, become a standard research tool for tissue‐based studies. All types of in situ analysis can be applied to tissue microarrays, including immunohistochemistry, fluorescence in situ hybridization, and RNA in situ hybridization. The TMA technology thus enables highly standardized, fast, and affordable translational research studies of unprecedented scale that substantially facilitate translational research.
SAGE
Authors: Blackshaw Seth
Published: July 2005

Serial analysis of gene expression (SAGE) has emerged in the past decade as a powerful tool for gene expression profiling. This article outlines the details of SAGE analysis, discusses the advantages and disadvantages of SAGE relative to microarray‐based approaches to expression profiling, and outlines important considerations to keep in mind when deciding how to design an experiment using SAGE.
Core methodologies
Authors: Cagney Gerard
Published: July 2005

The techniques in proteomics involve the identification of proteins using mass spectrometry. In this section, the procedures needed to (1) prepare proteomics samples, (2) analyze them by mass spectrometry, and (3) interpret the spectra and identify the component proteins are described.
Separation‐dependent approaches for protein expression profiling
Authors: Dunn Michael J. , Pennington Stephen R.
Published: July 2005

The depth and breadth of genomic data now available for a wide variety of prokaryotic and eukaryotic organisms provides a previously unimagined opportunity to perform comprehensive profiling studies of patterns of protein expression in complex biological systems that will result in new insights into cellular functions that determine biologically relevant phenotypes. In this chapter, we give an introduction to protein expression profiling in which the individual proteins in a complex sample are separated prior to semiquantitative analysis. We outline the alternative approaches based either on the use of one‐ and two‐dimensional gel electrophoresis or on the application of so‐called gel‐free methods based on the use of liquid chromatography coupled either on‐ or off‐line to mass spectrometry.
Protein arrays
Authors: Murphy Derek , Cahill Dolores J.
Published: July 2005

Protein array technology is becoming an increasingly important tool in the drive toward proteome‐scale analysis of protein activity and interactions. Presently, this technology compliments the more traditional methods for proteomic analysis, including two‐dimensional gel electrophoresis/chromatography and mass spectrometry. While the task of producing a “whole‐proteome” chip, containing active proteins, is a daunting one, current protein and antibody arrays represent the first steps toward that goal. In this review, we discuss current approaches for the generation of protein arrays, and their applications, including their use in the study of protein–protein, protein–nucleic acid, enzyme–substrate, and so on, interactions. Potential applications of protein arrays in interaction screening, such as compound–protein interactions are also discussed.
Quantum dots for multiparameter measurements
Authors: Bruchez Marcel P.
Published: July 2005

Quantum dot materials have emerged as powerful alternatives to conventional fluorescent molecules. Their optical properties are perfectly suited to the information‐intensive requirements of modern molecular and cellular biology assays, and have enabled a number of new ways of investigating cellular systems. Multicolor labeling with quantum dots allows collection of information on location, distribution, and abundance of multiple proteins in cellular and blot‐based systems with ratio‐based quantitation. The brightness and photostability of these materials provide researchers the means to investigate protein dynamics and changes in cellular and animal models over physiologically relevant timescales, and in situations where organic fluorescence probes fail. The spectral properties can be used effectively to extend the capability of multiplexed assays using multicolor beads as assay supports that are easily decoded to provide quantitative information on nucleic acids and proteins. A variety of researchers exploit these properties to open new avenues for biological investigation of the action and interactions of many molecules simultaneously.
Imaging protein function using fluorescence lifetime imaging microscopy (
FLIM
)
Authors: Gu Yan , Zicha Daniel
Published: July 2005

Fluorescence lifetime has been used in various protein function studies in both fixed and living cells, including contrast enhancement, colocalization, and interactions. In this review, current FLIM (fluorescence lifetime imaging microscopy) technologies and data processing methodologies are briefly summarized. Special attention is paid to the lifetime retrieval of multicomponent complexes, where the combination of confocal‐based time‐domain FLIM with spectral unmixing technique can provide more accurate estimation. Typical examples of protein function interpretations using FLIM are also discussed.
Glycosylation
Authors: Cummings Richard D.
Published: July 2005

Glycosylation is an enzymatic process in which sugars are added to other molecules to produce a glycosylated product. The major classes of enzymes that catalyze the process of glycosylation are transferases that use sugar nucleotide and lipid‐linked sugar donors. Examples of the products of glycosylation reactions are glycoproteins, glycolipids, glycosaminoglycans, oligosaccharides, and polysaccharides. Glycosylation reactions occur in all animals, plants, fungi, and microorganisms. In animals, glycosylation reactions occur mainly in the cytoplasm, endoplasmic reticulum, Golgi apparatus, and the plasma membrane. Glycans are important in many aspects of cellular and developmental regulation, and defects in glycosylation in humans and animals result in developmental abnormalities and embryonic death. Glycosylation is a common and essential process in all organisms.
Large complexes by
X
‐ray methods
Authors: Nissen Poul
Published: July 2005

The atomic structures of large complexes such as ribosomes and viruses can be solved by X‐ray crystallography. The purification and crystallization, together with data collection and crystallographic phasing, all present unusual problems compared to ordinary high‐throughput crystallography. Yet, several examples show how these obstacles can be solved.
Microbial sequence assembly
Authors: Weinstock George
Published: July 2005

Microbial genomes are assembled by the whole‐genome shotgun method, where random sequencing is performed to high redundancy and the sequencing reads are assembled en masse. Although the early microbial genome projects relied on a large insert clone tiling path and a clone‐by‐clone sequencing approach, current assembly software makes it possible to overcome challenges posed by repeated sequences and perform whole‐genome shotgun assemblies.
Errors in sequence assembly and corrections
Authors: Tammi Martti T. , Andersson Björn
Published: July 2005

The shotgun sequencing method is the most economical and easily automated sequencing technique and has thus become the method of choice. Computer software is used to put the pieces together very much like a jigsaw puzzle, but they can usually only produce a good estimate of a correct assembly, and extensive manual finishing is needed to generate the final sequence.
Pair hidden
M
arkov models
Authors: Alexandersson Marina , Bray Nicolas , Pachter Lior
Published: July 2005

We describe pair hidden Markov models, with an emphasis on their relationship to evolutionary models and hidden Markov models. We then explain the statistical interpretation of alignment with pair hidden Markov models, and highlight connections to the Needleman–Wunsch algorithm and other dynamic programming–based alignment algorithms.
Exonic splicing enhancers and exonic splicing silencers
Authors: Mount Stephen M.
Published: July 2005

Splicing signals that promote splicing and lie within exons are known as exonic splicing enhancers (ESEs), while signals within exons that repress splicing are known as exonic splicing silencers (ESSs). Both ESEs and ESSs act in conjunction with more highly conserved splicing signals at the two splice sites. ESEs are bound and activated by splicing factors known as SR proteins that are thought to act by recruiting core splicing factors such as the U1 snRNP or U2AF to appropriate splice sites. The mechanism of action of ESSs is less well understood and may be more variable. A variety of methods, both experimental and computational, have been used successfully to identify functional ESEs and ESSs; mutations in these splicing signals are increasingly recognized as responsible for human genetic disease.
Gene finding using multiple related species: a classification approach
Authors: Kellis Manolis
Published: July 2005

Three years after the initial sequencing of the human genome, the actual number of functional human genes remains uncertain. Several expression‐based analyses still argue for a hundred thousand transcribed genes, whereas more conservative estimates range between 20 000 and 25 000 genes. The central question in such debates still remains: what constitutes arealgene? In this paper, we address this question and present a comparative genomics approach for systematic gene identification, which observes gene‐specific signatures of evolutionary selection across multiple related species. First, we formulate the gene identification problem as a classification problem between genes and noncoding regions, on the basis of their distinct patterns of nucleotide change. We then summarize the results of applying this approach to reannotate the yeast genome, with changes affecting nearly 15% of all genes, and the rejection of more than 500 previously annotated genes. Finally, we discuss the implications of this analysis on understanding the human genome, and strategies for the systematic reannotation of higher eukaryotes.
Protein domains in eukaryotic signal transduction systems
Authors: Hofmann Kay
Published: July 2005

Eukaryotic proteins involved in signal transduction processes are frequently characterized by a modular architecture. These modules, also known as functional domains, are able to fold independently from the rest of the molecule. Typically, they also fulfill particular unit functions that can be separated from each other. Eukaryotic cells must respond to a large array of biological stimuli, and evolution has invented a sophisticated signal transduction network consisting of many different components to cope with the situation. Despite that complexity, the analysis of signaling proteins on the level of functional domains reveals a number of recurrent motifs. For most signaling systems, the unit functions of signal generation, signal detection, and signal destruction are carried out by classes of dedicated functional domains. While the similarity within those classes reflects a similar signaling mechanism, the required specificity is either conferred by the subtle differences between the class members or by highly specific targeting domains. Key examples for highly modularized signal transduction systems include protein phosphorylation or ubiquitination, GTPase signaling, and the multiadaptor mechanism of apoptosis signaling.
Large‐scale protein annotation
Authors: Kummerfeld Sarah K.
Published: July 2005

In recent years, genome projects have scaled up production so that they are now producing hundreds of protein sequences everyday. This has created a wealth of sequence data and raises several questions, such as: (1) what do these proteins do? (2) how do they fold? (3) what are their evolutionary relationships? Large‐scale protein annotation aims to address these questions using approaches that can quickly be applied to millions of proteins. This review traces the annotation of a hypothetical proteome in order to illustrate the computational techniques and data sources available for large‐scale annotation. We begin by outlining some of the most extensive catalogs of experimentally determined protein annotation and then discuss how homology methods can be used to relate these small‐ to medium‐scale information sources to the large‐scale annotation problem. Finally, we discuss some of the biological questions that are being addressed now that we have whole‐proteome annotations.
IMPALA
/
RPS
‐
BLAST
/
PSI
‐
BLAST
in protein sequence analysis
Authors: Wolf Yuri I.
Published: July 2005

Pairwise sequence comparison works well if the sequence similarity is high; as the similarity decreases, alignment scores become less and less reliable. Profile‐based approaches allow to extend the analysis into the “twilight zone”. Several NCBI tools – PSI‐BLAST, IMPALA, and RPS‐BLAST – can be used to iteratively build position‐specific scoring matrices and use them in direct (query profile against a sequence database) and reverse (query sequence against a profile database) similarity searches.
Phylogenetic analysis of
BLAST
results
Authors: Brinkman Fiona S. L.
Published: July 2005

BLAST (Basic Local Alignment Search Theorem) is one of the most elegant, and widely used bioinformatics analysis developed to date. Like many bioinformatic analyses, BLAST uses evolutionary theory as the basis for its assumptions. Therefore, an understanding of evolutionary theory is critical to the appropriate interpretation, and further analysis, of BLAST results. Viewing essentially one‐dimensional BLAST analysis from the perspective of a two‐dimensional phylogenetic analysis has a number of benefits including more accurate identification of the true “top hit”, delineation of gene families, identification of true homologs, and improved functional assignment of orthologs and paralogs. Performing such phylogenetic analyses has become easier, now that semiautomated methods have been developed that permit rough phylogenetic overviews of the data. However, it should be emphasized that phylogenetic analysis must often be customized for a given experiment or research question. Such issues are relevant not only to the further analysis of a BLAST output, but also to similar analyses of outputs from other widely used algorithms for rapid database search. Critical analysis of results is becoming increasingly important as sequence databases increase in both size and complexity – and as we begin to understand that even these large sequence databases are only scratching the surface of the true complexity and variety of sequences that exist in nature.
Data standardization and the
HUPO
proteomics standards initiative
Authors: Hermjakob Henning , Taylor Chris , Orchard Sandra , Zhu Weimin , Apweiler Rolf
Published: July 2005

The Proteomics Standards Initiative, a work group of the Human Proteome Organization, defines community standards for data representation in proteomics to facilitate data comparison, exchange, and verification.
Ontologies for information retrieval
Authors: Hersh William Richard
Published: July 2005

The goal of this review is to describe ontologies used for information retrieval (IR). We will begin with an overview of IR and its processes, followed by a description of how ontologies are used for IR, with particular emphasis on biomedical systems. Ontologies in general, the Gene Ontology (GO), and the Unified Medical Language System (UMLS) have been described in previous chapters. The explosion of data from new genomics and related research technologies provide a strong use case for the better understanding and improvement of IR systems.
Proteomics data representation and management
Authors: Paton Norman W. , Jones Andrew , Oliver Stephen G.
Published: July 2005

Proteomics is rapidly evolving into a high‐throughput technology, in which substantial studies are conducted on samples from a wide range of physiological, developmental, or pathological conditions. This gives rise to a need for techniques and technologies that enable the systematic description and capture of experimental data and metadata, which will allow for the archiving, sharing, and analysis of proteomic data sets. This chapter identifies the different aspects of an experiment that must be captured, and the derived information that underpins the interpretation of such data.
Gibbs sampling and bioinformatics
Authors: Liu Xiaole Shirley
Published: July 2005

Gibbs sampling is one of the best‐known Markov chain Monte Carlo methods. Its first and most popular application to bioinformatics is the sequence motif finding problem. Since then, Gibbs sampling has been successfully applied to many other interesting genomics and bioinformatics problems, especially haplotype inference and microarray biclustering.
Packaging, Cosmetics and Pharmaceuticals
Authors: Rosette Jack L. ,   Updated by Staff
Published: July 2005

Cosmetics and pharmaceuticals each have their own special packaging requirements, although the primary purpose of packaging for both is to provide a means to store and distribute the product until the entire contents of the package are used. Cosmetic packaging is used to enhance the image of the product, and though pharmaceutical packaging has the same basic objectives, product stability and safe packaging requirements dictate different parameters regarding tampering prevention and child safety requirements of the FDA and the Consumer Product Safety Commission.

The FDA Rule requires the use of tamper‐evident packaging on all over‐the‐counter drugs and some cosmetics. However, if a product in an adulterated form could harm a consumer, manufacturers have the responsibility of protecting the product and consumer against tampering, meaning that tamper‐evident packaging transcends FDA regulations. No single feature is best for all products and all features can be violated in some manner, but effective tamper‐evident features provide greater difficulty in doing so. Consumers should be aware of what to look for in tamper‐evident packaging and pay attention to what product is being used.
Toluenediamine
Authors: Cartolano Anthony R.
Published: July 2005

Toluenediamine (diaminotoluene,m‐TDA) is an important industrial chemical intermediate; it is produced in the largest volume of any arylamine and is the lowest priced diamine. The principal use for TDA is in the manufacture of toluenediisocyanate (TDI), the predominant diisocyanate in the flexible foams and elastomers industries. Although all six possible toluenediamine isomers are made in the commercial synthesis, only two products are available commercially. The aromatic toluenediamines undergo typical amine reactions. The general chemistry is similar to that of the phenylenediamines or the cyclohexanediamines. Reactions of industrial importance involving commercial toluenediamines include phosgenation, ring alkylation, alkoxylation, and diazotization. Dinitrotoluenes can be catalytically hydrogenated to toluenediamines under a wide variety of temperatures, pressures, and solvents. Toluenediamine is classified as toxic and is readily absorbed through the skin, which is the major route of human exposure.
Packaging, Food
Authors: Brody Aaron L.
Published: July 2005

The primary purpose of food packaging is to protect food against environmental contaminants. Each food category, eg, ambient temperature shelf stable, frozen, or chilled, has different requirements. Generally, product processing must be integrated with the package to optimize shelf‐life objective. Thus canned foods are both heated and hermetically sealed to exclude microbiological recontamination; dry foods are sealed against moisture access; frozen foods must be maintained at low temperatures and protected against moisture loss; and chilled foods are refrigerated while controlling the transmission of both moisture and air.

The most widely used packaging materials are paper and paperboard employed mostly in distribution channels. Second are metals; aluminum for cans to contain carbonated beverages and beer dominates in this category. Steel is applied for vacuum packaged foods. Glass has been declining as a package material because of weight, relative fragility, and high energy consumption. Plastic materials constitute only about 20% of the mass of package materials, but contain proportionately larger amount of food because of low densities and exceptional surface‐to‐volume ratio to achieve functionality. A variety of plastic materials is used for packaging depending on the food requirements, eg, polyethylenes, polyesters, polypropylenes, polystyrenes, nylons, poly(vinyl chlorides), etc. Among the structures employed are extrusion and injection blow‐molded bottles, thermoformed trays and cast or blown films. High gas barrier plastics are coated, coextruded, or laminated to structural plastics to enhance properties.
Light Emitting Diodes
Authors: Schubert E. Fred , Gessmann Thomas , Kim Jong Kyu
Published: July 2005

Inorganic semiconductor light‐emitting diodes (LEDs) are environmentally benign and have already found widespread use as indicator lights, large‐area displays, and signage applications. In addition, LEDs are very promising candidates for future energy‐saving light sources suitable for office and home lighting applications. Today, the entire visible spectrum can be covered by light‐emitting semiconductors: AlGaInP and AlGaInN compound semiconductors are capable of emission in the red to yellow wavelength range and ultraviolet (uv) to green wavelength range, respectively. Currently, two basic approaches exist for white light sources: The combination of one or more phosphorescent materials with a semiconductor LED and the use of multiple LEDs emitting at complementary wavelengths. Both approaches are suitable for high efficiency sources that have the potential to replace incandescent and fluorescent lights. In this article, the properties of inorganic LEDs will be presented, including emission spectra, electrical characteristics, and current‐flow patterns. Structures providing high internal quantum efficiency, namely, heterostructures and multiple quantum well structures, will be discussed. Advanced techniques enhancing the external quantum efficiency will be reviewed, including resonant‐cavities, die shaping (chip shaping), omnidirectional reflectors, and photonic crystals. Different approaches to white LEDs will be presented and figures‐of‐merit such as the color rendering index, luminous efficacy, and luminous efficiency will be explained. Finally, the packaging of low power and high power LED dies will be discussed.
Nuclear Power Facilities, Safety
Authors: Taylor John J.
Published: July 2005

Safety has played a dominant role in the ability to generate electricity by nuclear means because large quantities of highly radioactive fission products are generated with the energy from fission. Strict control is maintained over these radioactive materials to assure that public and worker health and safety are protected. The basic safety principles, defense‐in‐depth design philosophy, and key safety design features that apply to all nuclear facilities are discussed. Specific examples are given from nuclear power plant design. The methods of assessment of safety are described, both for self‐assessment and independent assessment. The roles of industry and government in the assessment process are outlined. Comparative risks of nuclear power are substantially lower than most other methods of generating electricity. The specific safety characteristics of the nuclear power plant that generates the electricity, and of the nuclear fuel cycle, which functions to produce nuclear fuel and dispose of radioactive wastes are each given. Special focus is placed on the safe disposal of spent fuel and radioactive waste. The basic radiation exposure and health standards which establish the foundation of public and worker protection are cited. The safety of future nuclear power plants is summarized.
Sensors
Authors: Hughes Robert C. , Ricco A. J. , Butler M. A. , Martin S. J.
Published: July 2005

Sensor technology is being revolutionized by advances in microelectronics and optoelectronics. Thus, modern sensor systems almost always include data acquisition capabilities. Rapid advances in sensor technology have increased the difficulty of the task of finding the best sensor system for a given application. A generic scheme for decision‐making is presented. Sensors, generally far from perfect, are often expected to function in hostile environments and to be immune to interference. A variety of sensor technologies are discussed. The most common is silicon processing technology, in which the sensing elements are micromachined into the same chip as the integrated circuit. Also possible are hybrid chips joined after the integrated circuit is formed. Photodetectors, smart sensors, and chemical sensors may be based on silicon processing technology. Other technologies involve the use of acoustic waves, optical fibers, electrochemical systems, and semiconducting metal oxides.
World's Major Irrigation Areas
Authors: Kijne Jacob W.
Published: July 2005

Worldwide, 70% of the water withdrawals is applied to agriculture. Irrigated agriculture is practiced on about 20% of the world's agricultural land, but it produces 40% of the world's food and fiber. Increasingly, the source of irrigation water is pumped groundwater, which leads to widespread mining of aquifers. More and more fields are no longer irrigated through furrows, but by pressurized systems, such as sprinkler and drip irrigation, which provide better control over application and distribution of water.

Irrigation objectives have changed over time from prevention of famines and flood control to maximum production per unit land. Because of increased water scarcity and concern about manmade environmental degradation, irrigation performance is now assessed for production per unit water, food security, poverty alleviation, and environmental security.

The management of large‐scale irrigation systems in developing countries used to be done by state institutions (e.g., irrigation departments). Now the operation and management, including fee collection, are often turned over to the farmers. Because of severe competition for water in many countries, irrigation management is challenged to produce more crops with less water while minimizing the adverse environmental impacts.
Soil Salinity
Authors: Corwin Dennis L.
Published: July 2005

Soil salinity is defined as the total salts present in the liquid portion of the soil. The primary significance of soil salinity lies in its effect on crop productivity. Salinity limits plant water uptake because of reduced osmotic potential, making the extraction of water from the soil more difficult. Soil salinity is generally associated with irrigated agricultural soils and soils with shallow depths to groundwater. Worldwide, over 20 million ha of agricultural land are severely affected by salinity. A general discussion of the sources, effects, global impacts, laboratory and field methods of measurement, and plant tolerance of soil salinity is presented. In particular, recent advances in field measurement and mapping of soil salinity are discussed. The concise discussion is designed to provide a basic understanding of soil salinity from an environmental and agricultural perspective.
Occurrence of Organochlorine Pesticides in Vegetables Grown on Untreated Soils from an Agricultural Watershed
Authors: Gonzalez Mariana , Miglioranza Karina S. B. , De Moreno Julia E. Aizpún , Moreno Víctor J.
Published: July 2005

Organochlorine pesticides (OCPs) are compounds of particular concern in the environment because of their recalcitrance, global transport, distribution, and toxicity, which lead to include them into the group of persistent organic pollutants. The impact of soil contaminants on human health and accumulation in food crops is relevant because of increased dietary exposure of consumers. Organic agriculture has developed rapidly during the last decade on the assumption that such food is free of synthetic pesticides. Although it is likely that lower pesticide residues are found in organically grown vegetables, it has been demonstrated that these produce can reach similar pesticide levels to those conventionally grown. Topographic position, wind dispersion, and neighboring farms are the main factors affecting organic products. Moreover, the use of pine needles as soil amendments can enhance the OCP levels, because they are known to accumulate highly lipophilic pollutants from the atmosphere. Vegetables grown on untreated soils accumulated OCPs efficiently from both air and soil. The main pesticides found involved, endosulfans currently in use, DDTs and HCHs, which are banned or restricted. All OCP levels were below the maximum residue limits (MRL) considered by the Codex Alimentarius. Therefore, ecosystem factors, such as pesticide runoff, drift from pesticide used by neighboring farming, volatilization, leaching, and wash out, impact on the occurrence of OCPs in vegetables grown on untreated soils.
Water Logging: Topographic and Agricultural Impacts
Authors: Madramootoo Chandra
Published: July 2005

Water logging occurs on poorly drained soils. Under periods of heavy precipitation or snowmelt, water percolates very slowly, and soils become wet in short periods of time. Some soils have inherently low ability to infiltrate and hydraulic conductivity, especially heavier clay soils. Soil compaction because of heavy farm equipment further reduces bulk density, which in turn reduces the ability to infiltrate soil. The result is that the water table accretes and may eventually rise to the land surface. High‐intensity rainfalls also lead to ponding of water on the soil surface. These conditions of surface ponding, a saturated soil profile, and gradual rise of the water table to the soil surface all lead to water logging.