bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoacoustic Spectroscopy
Authors: Harren Frans J. M. , Persijn Stefan , Cristescu Simona M.
Published: March 2011

After a short introduction and description of particular features of the equipment used, attention is centered on applications. Solids, surfaces, and solutions have been studied by photoacoustic (PA) spectroscopy; recent work is quoted. Gas‐phase investigations are discussed with emphasis on trace gas detection. Especially, applications in biology and human health are considered.
Metrology of Time and Frequency
Authors: Arias Felicitas , Bauch Andreas
Published: March 2011

This chapter provides a concise overview of the current status of time and frequency metrology. The definition of the time unit and of time scales is given, and the standards and procedures to realize them are described. The measures by which their properties are characterized are explained. The comparison of remote standards is discussed to the extent that it is a prerequisite for the realization of a world reference time scale by the Bureau International des Poids et Mesures (BIPM). Only a brief account is given on the various means of disseminating time and the wide applications thereof. The reader is invited to use the literature in theFurther Readingsection as well as the numerous references to get a deeper insight into the field.
Metrology in Medicine
Authors: Macdonald Rainer , Mieke Stephan
Published: March 2011

Physical, chemical, and biological measurements are important essentials in medical diagnosis for the prevention and treatment of disease as well as for risk assessment and monitoring of patients. Hence, measurement results that are relevant to medical diagnosis must be accurate, reliable, and comparable between different places and over time to ensure optimum patient care as well as the most efficient use of available health care funds. To ensure that medical measurement results are of known quality and to improve their accuracy and reliability, standards, reference methods, certified reference materials, and calibrations are needed. In this article, the peculiarities of medical measurements are discussed and problems encountered in fulfilling the above‐mentioned requirements are pointed out.
Viroids
Authors: Flores Ricardo , Daròs José‐Antonio , Hernández Carmen , Di Serio Francesco
Published: March 2011

Viroids are infectious, nonprotein‐coding, highly structured small circularribonucleic acids(RNAs) able to replicate autonomously and induce diseases in higher plants. Viroids and viruses differ in structure, function and evolutionary origin (with the former regarded as relics of a primitive RNA world). Viroids are classified into the familiesPospiviroidaeandAvsunviroidae, the members of which replicate in the nucleus and chloroplast, respectively, through an RNA‐based rolling circle mechanism with three steps catalysed by: (i) hostdeoxyribonucleic acid (DNA)‐dependent RNA polymerasesredirected to accept RNA templates, (ii) processing enzymes or, in the familyAvsunviroidae, hammerhead ribozymes and (iii)RNA ligases. When infecting a cell, the viroid RNA must travel to its replication organelle, with the resulting progeny moving cell‐to‐cell through plasmodesmata and reaching distal parts through the phloem. Pathogenesis could be triggered by the replicating viroid itself, or via RNA silencing. Viroids are detected by nucleic acid‐based approaches, some can be eliminated from infected plants by meristem tip culturing, and biotechnological approaches are being developed for their control.

Key Concepts:

Viroids are small nonprotein‐coding RNAs that infect, replicate and induce disease in higher plants.

Viroids differ from viruses in fundamental aspects that include structure, function and evolutionary origin.

Viroids are classified into the familiesPospiviroidae(nuclear viroids) andAvsunviroidae(chloroplastic viroids).

Viroid RNAs adopt compact secondary structures additionally stabilised by elements of tertiary structure.

Viroids replicate through a rolling circle mechanism with only RNA intermediates and enzyme or ribozyme processing.

Different viroids have distinct host ranges and closely related viroids display cross‐protection effects when co‐infecting a common host.

Viroids move intracellularly, cell‐to‐cell through plasmodesmata, and long distance through the phloem.

Viroids may infect their host plants latently or induce different pathogenic alterations including death.

Viroids propagate in their hosts as a population of closely related variants (quasispecies).

Viroids are considered molecular fossils of the RNA world postulated to have preceded our present world dominated by DNA and proteins.
Seeds
Authors: Black Michael
Published: March 2011

In the seed‐bearing plants (angiosperms and gymnosperms), the embryo‐containing seed develops from the fertilised ovule. Other tissues might also be present in the mature seed such as the endosperm (angiosperms) and the megagametophytic tissue in gymnosperms. During its formation, storage reserves are deposited in various parts of the seed. The structural and physiological features that develop during transition of the ovule into a seed confer upon it properties that account for its greatly successful role in the life cycle of the dominant plants on earth. These include the reserves, the various dispersal mechanisms and in the majority of species, the ability to withstand desiccation, which is connected with the longevity of seeds in the ‘dry’ state. Seed dormancy, where present, serves later to determine the place and time of germination. Regulation of seed processes is achieved by control of gene expression, including by the hormones abscisic acid and gibberellin. Seeds were critically important in plant domestication and are currently important in plant biotechnology.

Key Concepts:

A seed develops from a fertilised ovule and consists of an embryo and other tissues of different developmental origins.

The seed occupies a key position in the life cycle of higher plants and accounts for the great success of angiosperms and gymnosperms.

During its development, the seed lays down relatively high proportions of storage reserves for the later support of early seedling growth.

In most species, seeds tolerate the desiccation that terminates their development and thereafter remain alive for long durations in a quiescent state.

Seeds develop various structural features that later aid their dispersal.

During development, seeds of many species become dormant, a condition that later blocks germination until after certain environmental signals have been experienced.

Regulation of gene expression by hormones and other factors is central to the various processes that occur in seeds.

Various features of seeds had a key role in plant domestication and the development of crop species.

Seeds are central to plant biotechnology and the design of new crop types.
Cotranslational Translocation of Proteins Into Microsomes: Methods
Authors: Pool Martin , Dobberstein Bernhard
Published: March 2011

Translocation of secretory and membrane proteins through the membrane of the endoplasmic reticulum involves a signal sequence on the nascent protein, a cytosolic receptor system and a translocation channel (translocon). The process can be reconstituted using a protein‐synthesising system and rough microsomes derived from the endoplasmic reticulum (ER) of eukaryotic cells. Applications of this system have realised substantial insights into the mechanisms of protein targeting to the ER membrane and the insertion of a nascent polypeptide into the membrane. The arrest of polypeptides at distinct stages of the targeting or insertion process yielded snapshots from the movement of a polypeptide across the membrane. This has allowed identification of components of the translocation machinery and the characterisation of their sequential involvement in targeting and translocation.

Key Concepts:

Many membrane transport processes can be studied with fragmented membranes.

Mechanical shearing of cellular membranes always results in closed vesicles.

Cellular membranes are self‐organising structures without corners and breaks.

Reconstitution of cellular subfunctions is a very efficient way to characterise cellular processes at the molecular level.

When a system is too complex, then study first its parts.

Generating reaction intermediates blocked at defined steps allows complex processes to be broken down into simpler and more tractable subreactions.
Santalales (Including Mistletoes)
Authors: Nickrent Daniel L
Published: March 2011

Mistletoes are flowering plants in the sandalwood order (Santalales) that parasitise tree branches. They evolved five separate times in the order and are today represented by 88 genera and nearly 1600 species. Loranthaceae (
c
. 1000 species) and Viscaceae (550 species) have the highest species diversity. In South America

Misodendrum

(a parasite of

Nothofagus

) is the first to have evolved the mistletoe habit ca. 80 million years ago. The family Amphorogynaceae is of interest because some of its members are transitional between root and stem parasites. Many mistletoes have developed mutualistic relationships with birds that act as both pollinators and seed dispersers. Although some mistletoes are serious pathogens of forest and commercial trees (e.g.

Arceuthobium

), the vast majority are benign and in some cases beneficial to humans (e.g.

Viscum album

for anticancer drugs). Mistletoes play important roles in many forest ecosystems and their loss results in decreases in faunal diversity, thus making them keystone species.

Key Concepts:

A mistletoe is a branch parasite in the sandalwood order (Santalales).

Mistletoes have evolved from root parasitic ancestors five times independently in five different families: Misodendraceae, Loranthaceae, Santalaceae, Amphorogynaceae and Viscaceae.

The first lineage to evolve the mistletoe habit is
Misodendrum
, a South American parasite on southern hemisphere beech (
Nothofagus
).

Most mistletoe species are found in the families Loranthaceae (
c
. 1000 species) and Viscaceae (550 species).

Loranthaceae evolved on the Gondwanan supercontinent and subsequently spread from Antarctica to South America, Australia, New Zealand, Asia and Africa.

Many mistletoes have developed mutualistic relationships with birds that serve as both pollinators and seed dispersers.

Some mistletoes such as
Arceuthobium
are important pathogens of forest trees, whereas most are beneficial and even keystone species in forest ecosystems.
Chromosomes and Chromatin
Authors: Paulson James R , Vagnarelli Paola
Published: March 2011

Chromosomes are structures within the nuclei of eukaryotic cells that containdeoxyribonucleic acid(DNA) combined with proteins. Chromatin refers to the material of the chromosomes – DNA plus proteins. Before DNA replication, each chromosome contains a single, very long DNA molecule that basically runs from one end of the chromosome to the other. Core histone proteins package segments of this DNA molecule into nucleosomes, and linker histones further compact the resulting ‘string of beads’ into a 30‐nm chromatin fibre. In mitotic chromosomes, scaffold proteins fold the chromatin fibre into loops along its length. Chromosomes are very dynamic structures and take several forms, but the basic organisation is always related to the structure of mitotic chromosomes. The location of chromosomes in the nucleus, the nature of the loops and modifications to the chromatin fibre are thought to be important in determining which DNA sequences are made available for transcription and other processes.

Key Concepts:

In eukaryotic cells, genes are located in chromosomes in the cell nucleus.

Before the DNA has been replicated, a chromosome consists of a single very long DNA double helix that is highly coiled and folded by proteins.

Five major types of histone proteins, all of them highly basic, neutralise much of the DNA's negative charge and package the DNA into nucleosomes and 30‐nm fibres.

TheN‐terminal tails of core histones are intrinsically disordered, allowing them to interact with many other proteins and undergo various posttranslational modifications.

Transcriptional activation of genes, or readiness for transcriptional activation, is associated with histone acetylation, and inactivation is generally associated with histone methylation.

In mitotic chromosomes, the chromatin fibre is folded into loops by attachment to a scaffold of nonhistone proteins.

Mitotic chromosome condensation appears to involve two components: compaction of the chromatin at the onset of mitosis, which involves phosphorylation of chromosomal proteins, and establishment of a robust architecture that can withstand spindle forces, which involves condensin.

The various chromosome forms that are seen throughout the cell cycle or the life cycle of the organism have closely related structures.

A chromosome during interphase retains some aspects of the structure it had during mitosis and is confined to a distinct ‘territory’ within the interphase nucleus.

Chromosome banding and chromosome painting are medically important for detecting chromosome abnormalities such as breaks, fusions, translocations and aneuploidy and can be used to track chromosomal rearrangements that have occurred during evolution.
Retinoblastoma
Authors: Lohmann Dietmar R , Gallie Brenda L
Published: March 2011

Retinoblastoma is a malignant tumour that originates in the developing retina and is usually diagnosed in children under age of 5 years. Mutations in both alleles of the tumour suppressor gene

RB1

are a prerequisite for this tumour. In nonheritable retinoblastoma the two mutations have occurred in somatic cells and are not passed to offspring. Germline mutations in one allele of the

RB1

gene cause heritable predisposition to retinoblastoma and a spectrum of other tumours (second cancers). In families this trait is autosomal dominant with variable phenotypic expression. Analysis of genotype–phenotype associations has shown that the mean number of tumour foci that develop in carriers of mutant

RB1

alleles becomes smaller depending on which, and to what extent, functions of the normal allele are retained. The function of the

RB1

gene product, pRb, that is understood best is as a gatekeeper that negatively regulates progression through G
1
phase of the cell cycle. However, a more important role in cancer progression may be prevention of
deoxyribonucleic acid
(DNA) instability. Recently, the

RB1

gene was found to be imprinted, which may explain some of the observed parent‐of‐origin effects.

Key Concepts:

Two‐step mutational inactivation of the retinoblastoma gene (
RB1
) is a prerequisite for development of retinoblastoma.

Germline mutations in the
RB1
gene cause heritable retinoblastoma which is transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity.

Variable phenotypic expression of heritable retinoblastoma is in part explained by allelic heterogeneity of RB1 gene mutations.

In patients with nonheritable retinoblastoma, the two alleles of the retinoblastoma gene are inactivated by somatic mutations.

The human
RB1
gene is imprinted with skewed expression in favour of the maternal allele.
Alternative Splicing and Human Disease
Authors: Stamm Stefan
Published: March 2011

Almost all human protein coding genes undergo alternative splicing, and an increasing number of diseases is associated with the selection of ‘wrong’ splice sites. Alternative missplicing can be caused by
deoxyribonucleic acid
point mutations, changes in repetitive sequences or alterations in proteins that regulate splicing. The effect of these mutations can be evaluated by bioinformatic means, but these predictions need to be verified experimentally. With the exception of premature stop codons that are introduced by aberrantly spliced exons, the mechanism of pathological exon usage that leads to a disease is generally poorly understood. A pathological change in the activity of splicing factors typically results in numerous small changes in exon usage. Numerous screening efforts identified oligonucleotides and small molecular weight substances that can be tested as therapeutic approaches for diseases caused by missplicing.

Key Concepts:

Alternative splice site selection is regulated by combinatorial control through a network of protein–protein, protein–RNA and RNA–RNA interactions.

Mutations in the splice sites, exonic and intronic sequences lead to aberrant exon usage.

Mutations can cause exon skipping, a change in the degree of exon usage or activate sequences on the pre‐mRNA to become a new exon.

Synonymous mutations in exons can cause their aberrant usage, which can be a disease mechanism.

A pathological change in the activity of splicing regulatory proteins results in numerous, individually small changes of alternative exon usage.

Aberrant exon usage can be targeted by rationale therapies, several oligonucleotide‐based treatments are tested in clinical trials and small molecules were identified that change splice site selection by high‐throughput screens.
Balancing Selection in the Human Genome
Authors: Andrés Aida M
Published: March 2011

Balancing selection maintains advantageous diversity in populations by a variety of mechanisms. As a source for functional polymorphism, it contributes to the genetic and phenotypic diversity of present‐day human populations. Classically, most of our understanding of the influence of balancing selection in humans was based on few well‐known examples, but recent advances at the genome scale (made possible by newly available genomic databases and analytical methods) provide further insights on the influence and targets of balancing selection in humans. Such studies have pointed out the uniqueness of the MHC locus, but suggest that more typical cases of balancing selection exist. Our growing understanding of the targets of balancing selection in humans suggests that although this is not a pervasive force in the human genome, it has played a role in the maintenance of functionally relevant polymorphism in humans.

Key Concepts:

Balancing selection maintains genetic and phenotypic diversity in populations.

Different mechanisms constitute balancing selection, all of which maintain advantageous polymorphism in populations.

Balancing selection is not pervasive in humans, but it has shaped the evolution of critical genes for individual survival.

The MHC complex in chromosome 6 shows striking, and unique, genetic signatures of balancing selection.

Advantageous diversity for MHC‐dependent antigen presentation has shaped the patterns of diversity of diverse genomic loci.

The genetic signatures of balancing selection can be identified both by studying individual genes and by analysing genome‐wide patterns of diversity.

Genome‐wide analyses are key to identify previously unknown (and unsuspected) targets of natural selection.

Targets of balancing selection remain undiscovered in the human genome.
Sequence Finishing on New Platforms
Authors: van Tonder Andries J , Grafham Darren
Published: March 2011

In the past five years, next generation sequencing (NGS) technology platforms have been released and have become the tool of choice for sequencing genomes. Methods for sequence finishing have had to be updated to deal with the issues created by NGS platforms. Finishing begins with the assembling of the reads produced by the sequencing machines before computational gap closure is attempted. Remaining gaps are identified and suitable experimental techniques such as polymerase chain reactions are used to close these. Until recently, the aim for many genome sequencing projects has been to fully finish genomes. However, due to the time and cost associated with finishing, the majority of future genomes will only reach a high‐quality draft. New genome standards have had to be defined to better reflect the types of sequencing now being undertaken. Improvements to the current generation of sequencing machines along with the advent of the third‐generation technologies means that new ways of dealing with the data volume will need to be sought.

Key Concepts:

Next generation sequencing platforms have generated new issues for sequence finishing, which have required novel solutions.

Genome standards have had to be updated to better reflect NGS data.
Molecular Biology of Breast Cancer
Authors: Caffarel Maria M , Pensa Sara , Wickenden Julie A , Watson Christine J
Published: March 2011

Breast cancer is a common disease affecting approximately 1 in 10 women at some time in their lives. Moreover, it is not a single disease but is characterised by distinct pathological types with different clinical outcomes. In the past decade, considerable progress has been made in understanding these different cancer subtypes at the molecular level. In particular, global gene expression studies have identified five predominant subtypes that have unique expression signatures. Unlike many other cancers, where a hierarchy of genetic mutations that leads to tumorigenesis has been identified, breast tumours have diverse genetic mutations that affect a variety of signalling pathways. The recent discovery of
micro ribonucleic acids
(microRNAs) and their role in tumour metastasis has opened up a whole new area of research. Although some highly successful treatments have been developed, the challenge for the future is the development of individualised therapies that are specific to each patient's tumour type.

Key Concepts:

Breast cancer is a heterogeneous disease characterised by distinct pathological types with different outcomes.

Breast tumours have diverse genetic mutations that affect a variety of signalling pathways.

Breast tumours can be classified into different subgroups according to their molecular expression profiles.

It is not clear whether specific molecular pathways establish the subtype of breast cancer or whether different cell types become transformed and give rise to each tumour subtype.

Breast cancer patients would benefit from individual therapeutic regimens designed to treat their particular type of cancer.
Hsp70 Chaperones
Authors: Craig Elizabeth A , Marszalek Jaroslaw
Published: March 2011

Via their interaction with client proteins, Hsp70 molecular chaperone machines function in a variety of cellular processes, including protein folding, translocation of proteins across membranes and assembly/disassembly of protein complexes. Such machines are composed of a core Hsp70, as well as a J‐protein and a nucleotide exchange factor as co‐chaperones. These co‐factors regulate the cycle of adenosine triphosphate (ATP) hydrolysis and nucleotide exchange, which is critical for Hsp70's interaction with client proteins. Cellular compartments often contain multiple Hsp70s, J‐proteins and nucleotide exchange factors. The capabilities of Hsp70s to carry out diverse cellular functions can result from either specialisation of an Hsp70 or by interaction of a multifunctional Hsp70 with a suite of J‐protein co‐chaperones. The well‐studied Hsp70 systems of mitochondria provide an example of such modes of diversification and specialisation of Hsp70 machinery, which are applicable to other cellular compartments.

Key Concepts:

Fundamental biochemical properties of different Hsp70 systems are very similar, yet very adaptable.

Diversification of Hsp70 function is often due to multiple J‐protein partners.

Although most Hsp70s bind a broad array of peptide sequences, some have become specialised and have a very restricted binding specificity.
Aptamers
Authors: Gopinath Subash C. B.
Published: March 2011

Aptamers are artificial nucleic acid ligands that can be generated against a wide range of targets including amino acids, drugs, proteins, and other molecules. They are isolated from complex libraries of synthetic nucleic acid by an iterative process of adsorption, recovery, and reamplification. They have potential applications in analytical sensing devices, target validation, and as therapeutic agents. Aptamers are now widely accepted as substitutes for antibodies, especially in the diagnostic front. Aptamers are approved as drugs for therapeutics, and several aptamers are under clinical trials with the ultimate aim for commercialization.
Melendez‐Diaz v.Massachusetts—The Admissibility of Laboratory Reports
Authors: Layne DesPortes Betty
Published: March 2011

The Sixth Amendment of the US Constitution provides seven basic rights to the accused in criminal prosecutions, including the right “to be confronted with the witnesses against him.” This right is referred to as the right to confrontation and the provision is known as “the Confrontation Clause.” InMelendez‐Diaz v. Massachusetts, 129 S.Ct. 2527 (2009), the US Supreme Court continued the reformation of the Confrontation Clause that began 4 years before inCrawford v. Washington, 541 U.S. 36 (2004), which severed the right to confrontation from the rules of evidence concerning hearsay. InCrawford, the Court had held that the constitutional protections of the Confrontation Clause extended to all “testimonial statements” and that the right to confrontation was not satisfied by a mere consideration of the “reliability” of the statements to be presented; the right to confrontation required the reliability of the statements to be assessed by a particular procedure—by the in‐court presentation of witness testimony subjected to the rigors of cross‐examination. InMelendez‐Diaz, the Court continued to define “testimonial statements,” holding that laboratory reports of forensic analysis were “testimonial” in nature. This holding meant that for the forensic reports to be admissible over defense objection, the Confrontation Clause required the presentation of the forensic analyst for in‐court testimony with the opportunity for cross‐examination.
Ear Photographs: Examination and Forensic Potential
Authors: Monge Janet M.
Published: March 2011

Although the potential exists for the identification of humans based on measurement and observational features of the human ear, this potential has yet to be fully explored scientifically. As such, although it is tempting to apply both visual inspection and measurement criteria to exposed ears viewed in video surveillance, its efficacy in meeting evidential standards has yet to be established. Certainly a large amount of variation exists in the various features that compose the human ear but how those variations are patterned remains unknown on the individual, familial, and the population levels. Compounding these essential issues are difficulties in controlling for the quality and detail resolution of the visual representations (video and/or still photographic) used for comparisons within a forensic context.
Microbial Forensics
Authors: Budowle Bruce , Williamson Phillip C.
Published: March 2011

Our safety and security are constantly being challenged. One of the vulnerabilities is that due to a bioterrorism attack. There are many targets and many bioweapons that are easily accessed. The continued advancements in technology that benefit mankind can also be exploited for nefarious acts. Forensic science can contribute to criminal interdiction or the investigative response after an attack. The field of microbial forensics has been developed to provide another avenue in the goal toward forensic attribution. Microbial forensics is the scientific discipline dedicated to analyzing evidence from a bioterrorism act, biocrime, hoax, or inadvertent microorganism/toxin release for attribution purposes. Microbial forensics combines the practices of epidemiology with the characterization of microbial and microbial‐related evidence to assist in determining the specific source of the sample, in ways that are as individualizing as possible, and/or the methods, means, processes and locations involved to determine the identity of the perpetrator(s) of an attack. Because of the impact of microbial forensic evidence high quality assurance and quality control practices must be in place and the limitations of any analysis properly understood.
New Approaches to the Characterization of Drug Candidates by Solid‐StateNMR
Authors: Vogt Frederick G. , Clawson Jacalyn S. , Strohmeier Mark , Pham Tran N. , Watson Simon A. , Edwards Andrew J.
Published: March 2011

Solid‐state NMR (SSNMR) spectroscopy has been found to be very useful technique for pharmaceutical development. This technique is currently applied for the study of pharmaceutical solids, ranging from detailed structural studies of active pharmaceutical ingredients (APIs) forms to analysis of complex drug products and formulations. The study suggests that solid‐state structure of a pharmaceutical product can influence its properties, manufacturability, and stability. It is essential to regulate and control over solid‐state structure and subsequent properties. The studies show that SSNMR is closely related to the widely used technique of solution‐state NMR and possesses many of the same features. Further the study concludes that field of pharmaceutical SSNMR continues to advance at a rapid rate and will develop new molecular classes and new formulations and delivery modes in near future.
Stereoselective Reactions of Organoselenium Reagents Including Catalysis
Authors: Singh Fateh V. , Wirth Thomas
Published: March 2011

In the last decades, organoselenium chemistry has been developed as an important tool for synthetic and medicinal chemistry. The variety of organoselenium reagents has led to many versatile and new approaches in synthetic organic chemistry. Various synthetic moieties can be selectively introduced into complex molecules under very mild reaction conditions. The unique properties of selenium allow the development of novel and highly selective transformations, which can be employed for the synthesis of synthetic and naturally occurring chiral building blocks. This chapter highlights some recent developments of stereoselective reactions using organoselenium reagents including asymmetric catalysis.
Characterization and Validation of Cre‐Driver Mouse Lines
Authors: Gofflot Françoise , Wendling Olivia , Chartoire Nathalie , Birling Marie‐Christine , Warot Xavier , Auwerx Johan
Published: March 2011

Conditional gene manipulations in mice are increasingly popular strategies in biomedical research. These approaches rely on the production of conditional genetically engineered mutant mouse (GEMM) lines with mutations in protein‐encoding genes. These conditional GEMMs are then bred with one or several transgenic mouse lines expressing a site‐specific recombinase, most often the Cre recombinase, in a tissue‐specific manner. Conditional GEMMs can only be exploited if Cre transgenic mouse lines are available to generate somatic mutations, and thus the number of Cre transgenic lines has significantly increased over the last 15 years. Once produced, these transgenic lines must be validated for reliable, efficient, and specific Cre expression and Cre‐mediated recombination. In this overview, the minimum level of information that is ideally required to validate a Cre‐driver transgenic line is first discussed. The vagaries associated with validation procedures are considered next, and some solutions are proposed to assess the expression and activity of constitutive or inducible Cre recombinase before undertaking extensive breeding experiments and exhaustive phenotyping. Curr. Protoc. Mouse Biol. 1:1‐15. © 2011 by John Wiley & Sons, Inc.
Standardized Post‐Mortem Examination and Fixation Procedures for Mutant and Treated Mice
Authors: Antal Cristina , Muller Stéphanie , Wendling Olivia , Hérault Yann , Mark Manuel
Published: March 2011

A procedure for post‐mortem examination (or necropsy) of mice is provided. The aim is to obtain a “holistic” picture of organs and systems at the anatomical and histological levels. The major issue is tissue preservation, which is achieved by rapid transfer into a fixative solution, usually neutral buffered formalin. Fixation is the first of the four basic steps in histopathological analyses of tissues, which also include embedding, sectioning, and staining. The protocols provided here describe routine methods for tissue fixation, as these methods are integral parts of any necropsy procedure. There is also a Strategic Planning section that addresses the overall approach to histopathological evaluation, as well as specifics such as age and gender of the mice, cohort size, and controls. Curr. Protoc. Mouse Biol. 1:17‐53. © 2011 by John Wiley & Sons, Inc.
Assessment of Spontaneous Locomotor and Running Activity in Mice
Authors: Thomas Charles , Marcaletti Stefan , Feige Jérôme N.
Published: March 2011

The locomotor activity of laboratory mice is a global behavioral trait which can be valuable for the primary phenotyping of genetically engineered mouse models as well as mouse models of pathologies affecting the central and peripheral nervous systems, the musculoskeletal system, and the control of energy homeostasis. Basal levels of mouse locomotion can be recorded using infrared monitoring of movements, and further information can be gathered by giving the animal access to a running wheel, which will greatly enhance its spontaneous physical activity. Described here are two detailed protocols to evaluate basal locomotor activity and spontaneous wheel running. Curr. Protoc. Mouse Biol. 1:185‐198. © 2011 by John Wiley & Sons, Inc.
Design and Generation of Gene‐Targeting Vectors
Authors: Wefers Benedikt , Wurst Wolfgang , Kühn Ralf
Published: March 2011

This unit provides an overview of the major types of mutant alleles that can be generated by gene targeting in ES cells. It presents the growing public resources of premade gene targeting vectors, modified ES cells, and mutant mice. General guidelines for the design of targeting vectors are followed by protocols for the construction of vectors to generate knockout (KO), conditional KO, and subtle mutant alleles. Curr. Protoc. Mouse Biol. 1:199‐211. © 2011 by John Wiley & Sons, Inc.
Mouse Breeding and Colony Management
Authors: Ayadi Abdelkader , Ferrand Gisèle , Cruz Isabelle Goncalves da , Warot Xavier
Published: March 2011

The possibility to genetically modify the mouse genome has enabled the creation of numerous lines of genetically engineered mouse models (GEMMs). As a result, the demand for housing space in research facilities is increasing. Knowledge of the basis of mouse reproduction and of the methods to handle colonies of GEMMs is therefore mandatory to efficiently populate facilities. The mouse has a short generation period, produces large progenies, and can breed all year round. However, environmental parameters (bedding, diet, cage type, temperature, hygrometry, light, noise, and sanitary status) strongly influence the breeding efficiency and experimental data, and must be tightly controlled. Efficient GEMM colony management requires adequate recording of breeding and proper identification and genotyping of animals. Various mating types and breeding schemes can be used, depending on the type of studies conducted. The recent development of assisted reproduction methods helps circumvent some of the issues faced with those lines especially difficult to breed. Curr. Protoc. Mouse Biol. 1:239‐264. © 2011 by John Wiley & Sons, Inc.
Self‐Assembly and Shape Morphology of Liquid Crystalline Gold Metamaterials
Authors: Draper Michael , Saez Isabel M. , Cowling Stephen J. , Gai Pratibha , Heinrich Benoït , Donnio Bertrand , Guillon Daniel , Goodby John W.
Published: March 2011

Gold nanoparticles offer the possibility of creating metamaterials; however, such nanoparticles are not particularly stable. Conversely, liquid crystals offer the possibility of creating self‐organizing and self‐assembling materials, which can be designed to be relatively stable. Potentially, combining these two concepts could provide materials that can be induced to assemble in a controlled way and that would have unique optical properties. This article describes some of the groundwork made in the preparation of stable liquid‐crystalline metamaterials and the investigation of their structures and physical properties. In particular, spherically substituted materials are found to be deformed into tactoids with anisotropic properties, most notably their dielectric anisotropies.
Asymmetric Friedel–Crafts Reaction of Indoles with Ethyl Trifluoropyruvate Using a Copper(I)‐Bisoxazolidine Catalyst
Authors: Wolf Christian , Zhang Peng
Published: March 2011

Bisoxazolidine 1 is an effective ligand in the copper(I)‐catalyzed Friedel–Crafts reaction of alkyl trifluoropyruvates and indoles. A range of ethyl 2‐(3′‐indolyl)‐3,3,3‐trifluoro‐2‐hydroxypropanoates was produced in up to 99% yield and 94% ee within 30 min to 4 h. The effect of temperature on conversion and enantioselectivity proved to be substrate specific and was optimized individually. Of particular interest is that this method tolerates the presence of substituents in various positions in the indole ring. Yields ranging from 90–97% and ee values between 90 and 94% were obtained at optimized temperatures with substrates carrying substituents in position 1 or 7.
Approximate dynamic programming‐based control of distributed parameter systems
Authors: Joy Midhun , Kaisare Niket S.
Published: March 2011

The objective of this work is to extend the approximate dynamic programming (ADP) framework to online control of distributed parameter systems. The ADP framework involves using suboptimal control policies to identify the relevant regions of the state space and to generate a cost‐to‐go function approximation applicable in this region. We present model‐based value iteration and model‐free Q‐learning approaches for feedback control of an adiabatic plug flow reactor. The state dimension is reduced using appropriate model reduction and sensor placement techniques. We show that both the approaches provide better performance than the initial model predictive control and Proportional‐Integral‐Derivative (PID) controllers. Finally, an extension of ADP to the stochastic case with full state feedback is presented. Copyright © 2011 Curtin University of Technology and John Wiley & Sons, Ltd.
Identification of alien predators that should not be removed for controlling invasive crayfish threatening endangered odonates
Authors: Miyake Moe , Miyashita Tadashi
Published: March 2011

When multiple invasive species coexist in the same ecosystem and their diets change as they grow, determining whether to eradicate any particular invader is difficult because of complex predator–prey interactions.

A stable isotope food‐web analysis was conducted to explore an appropriate management strategy for three potential alien predators (snakehead Channa argus, bullfrog Rana catesbeiana, red‐eared slider turtle Trachemys scripta elegans) of invasive crayfish Procambarus clarkii that had severely reduced the densities of endangered odonates in a pond in Japan.

The stable isotope analysis demonstrated that medium‐ and small‐sized snakeheads primarily depended on crayfish and stone moroko Pseudorasbora parva. Both adult and juvenile bullfrogs depended on terrestrial arthropods, and juveniles exhibited a moderate dependence on crayfish. The turtle showed little dependence on crayfish.

These results suggest that eradication of snakeheads risks the possibility of mesopredator release, while such risk appears to be low in other alien predators. Copyright © 2011 John Wiley & Sons, Ltd.
Making Sense of Ecopreneurs' Decisions to Sell Up
Authors: Kearins Kate , Collins Eva
Published: March 2011

This article examines the phenomenon of values‐based firms being sold to larger mainstream firms. Its focus is on the sensemaking rationale offered by a New Zealand ecopreneur who sold an organic beverage company after 20 years at the helm. The company case study is presented through two enterprise development narratives based on alternative sensemaking modes. Key values‐related challenges arising in ecopreneurial business are identified, including (1) adhering to the founder's values, (2) growing the business sustainably, (3) deciding whether and when to expand ownership to cope with undercapitalization, (4) deciding who to bring in as new owners to ensure values alignment, (5) determining how and when the founder might leave and (6) ensuring the attractiveness of the sustainability values so that they might be retained. Other factors implicated in the sale of values‐based firms are also postulated. It is argued that, although ecopreneurs might be accused of selling out their principles by selling up, there is some evidence that eco‐brands are being maintained and that growth prospects could be improved after acquisition. Serial ecopreneurship may even extend social benefits. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
Destination of the C4 component of the prefixed brachial plexus
Authors: Hur Mi‐Sun , Woo Jung‐Su , Park Seon‐Young , Kang Bum‐Seung , Shin Chuog , Kim Ho‐Jeong , Lee Kyu‐Seok
Published: March 2011

This study was carried out to elucidate the destination of the C4 ventral ramus that forms the prefixed brachial plexus. A total of 43 sides of Korean adults (male, 22; female, 18; unknown: 3 and right, 23; left, 20) were investigated. The various C4 destinations and their frequencies were as follows: suprascapular nerve, 97.7% (42/43); musculocutaneous nerve, 79.1% (34/43); the axillary nerve, 48.8% (21/43); and the nerve to subclavius, 16.2% (7/43). The mean quantity of nerve fibers destined to the suprascapular, musculocutaneous, and axillary nerves and the nerve to subclavius was 441.8 ± 316.5 (Mean ± S.D.), 298.2 ± 209.8, 245.8 ± 239.0, and 66.4 ± 17.2, respectively. The mean nerve fibers number of C4 contributing to the brachial plexus was 983.6 ± 618.0 (range: 100–1729). The main component that contributes to the terminal nerves (suprascapular, musculocutaneous, axillary nerves, and nerve to subclavius) is C5. These results may be useful to surgeons and clinicians dealing with terminal nerves of the brachial plexus, especially the suprascapular, musculocutaneous, and axillary nerves. Clin. Anat. 24:717–720, 2011. © 2011 Wiley‐Liss, Inc.
Highly Stereoselective Total Synthesis of Fully Hydroxy‐Protected Mycolactones A and B and Their Stereoisomerization upon Deprotection
Authors: Wang Guangwei , Yin Ning , Negishi Ei‐ichi
Published: March 2011

Unprecedentedly efficient and highly (≥98 %) stereoselective syntheses of mycolactones A and B side chains relied heavily on Pd‐catalyzed alkenylation (Negishi version) and were completed in 11 longest linear steps from ethyl (S)‐3‐hydroxybutyrate in 12 % and 11 % overall yield, respectively, roughly corresponding to an average of 82 % yield per step. The synthesis of mycolactone core was realized by using Pd‐catalyzed alkenylallyl coupling and an epoxide‐opening reaction with a trialkylalkenylaluminate as key steps. Fully hydroxy‐protected mycolactones A and B of ≥98 % isomeric purity were synthesized successfully for the first time. However, unexpected 4:3–5:4 inseparable mixtures of mycolactones A and B were obtained upon deprotection.
Impact of androgen deprivation on physical well‐being in patients with prostate cancer
Authors: Sadetsky Natalia , Greene Kirsten , Cooperberg Matthew R. , Hubbard Alan , Carroll Peter R. , Satariano William
Published: March 2011

BACKGROUND:

As androgen deprivation therapy (ADT) becomes a standard of treatment for men with recurrent or metastatic prostate cancer, evaluation of adverse effects associated with this treatment is needed. In this study, the authors evaluated the effect of ADT administered as monotherapy and in combination with local treatment on physical well‐being in a longitudinal sample of men with prostate cancer.

METHODS:

Exposure to ADT was defined by 3 groups: local (local treatment only), combination (local treatment with adjuvant and/or neoadjuvant ADT), and primary ADT. Associations between exposure to ADT and physical well‐being measured by self‐reported health‐related quality of life outcomes over time were evaluated by repeated measures analysis using mixed modeling. Estimates adjusted for various clinical and demographic variables are reported.

RESULTS:

A total of 2922 men, who completed both pretreatment and follow‐up health‐related quality of life assessment, were identified from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. During 24 months of follow‐up, exposure to ADT was associated with worse physical well‐being compared with local treatment at all time points (P < .001). Being exposed to ADT as primary therapy was associated with more severe declines compared with combination therapy.

CONCLUSIONS:

The potential consequence of decline in physical well‐being in patients exposed to ADT has to be included in treatment decision making. Cancer 2011;. © 2011 American Cancer Society.
The Adolescent Outcome of Children with Attention Deficit Hyperactivity Disorder Treated with Methylphenidate or Methylphenidate Combined with Multimodal Behaviour Therapy: Results of a Naturalistic Follow‐up Study
Authors: van der Oord S. , Prins P. J. M. , Oosterlaan J. , Emmelkamp P. M. G.
Published: March 2011

Objective: Children with attention deficit hyperactivity disorder (ADHD) who participated in a randomized clinical trial, which compared a brief intensive multimodal behaviour therapy combined with optimally titrated methylphenidate to optimally titrated methylphenidate alone (n = 45), were re‐assessed at adolescence in a naturalistic follow‐up 4.5 to 7.5 years after treatment. Also a matched normal control group was recruited (n = 23).

Methods: Assessments at follow‐up included diagnostic status, ADHD symptoms, oppositional and conduct behaviour, substance abuse symptoms and parenting stress.

Results: Of the 24 adolescents participating in the follow‐up study, 50% still met diagnostic criteria for ADHD. There were no significant differences between adolescents at follow‐up and those lost for follow‐up. At follow‐up, adolescents in the combined treatment condition used significantly less medication than children in the methylphenidate condition; there were no other significant differences between the treatment conditions. The adolescents showed a significant decline in hyperactivity/impulsivity, oppositional and conduct disorder symptoms from post‐test to follow‐up. Only inattention symptoms increased from post‐test to follow‐up but not to pre‐test levels. The adolescents originally diagnosed with ADHD fared significantly worse than the matched controls on all outcomes, except on conduct disorder and substance abuse symptoms.

Conclusions: Our study shows in adolescents, diagnosed with ADHD in childhood, age‐dependent decline of ADHD symptoms, although they still fared significantly worse than matched normal controls. Implications of results are restricted by small samples size, and the results may be subject to chance findings and need replication before firm conclusions can be drawn. Copyright © 2011 John Wiley & Sons, Ltd.

Key Practitioner Message

Children treated with methylphenidate or methylphenidate combined with cognitive behaviour therapy were re‐assessed in adolescence 4.5 to 7.5 after end of treatment

Only 50% of the children diagnosed with ADHD still met ADHD criteria in adolescence

Children diagnosed with ADHD show age‐dependent decline of symptoms in adolescence, especially of hyperactivity/impulsivity, oppositional and conduct disorder symptoms

Adolescents diagnosed with ADHD in childhood fare significantly worse than matched controls on ADHD, oppositional symptoms and levels of parenting stress, but not on conduct disorder or substance abuse symptoms

Although interpretation of results is restricted by a small samples size, treatment with behavior therapy next to methylphenidate may not have additive effects on short-term outcome, but may cause long-term effects, i.e. less methylphenidate use in adolescence.