bluuebunny/crossref_metadata_2025 huggingface dataset:
Secretory Immunoglobulin A
Authors: Corthésy Blaise
Published: September 2013

Secretory immunoglobulin A (IgA) (SIgA) is the most abundant Ig produced at the surface of mucosal membranes in mammals. These very thin and sensitive barriers are challenged by occasional pathogenic microbes as well as by permanently residing commensal bacteria. Although not the unique guardian of mucosal epithelia, SIgA is an important component of the protective function guaranteeing maintenance of homoeostasis and wellness. Topics presented in this article include: (1) mechanisms involved in local induction of SIgA via T‐cell‐dependent and ‐independent pathways; (2) structure–function relationship in SIgA; (3) immunoregulatory role of SIgA vis‐à‐vis pathogens and commensals and (4) the unexpected contribution of SIgA in diseases. Because this is the most studied mucosal environment, most of the functional characteristics of SIgA are exemplified with respect to the gastrointestinal tract.

Key Concepts:

SIgA is the most abundant immunoglobulin produced at mucosal surfaces, and it exists in secretions in polymeric forms of high and low antigenic affinity/avidity.

The presence of secretory component in SIgA confers additional features including improved stability, proper anchoring in mucus and adequate localisation for optimal functions on the antibody.

Because epithelia in the gastrointestinal, respiratory and urogenital tracts are highly sensitive to invading environmental antigens, shielding of mucosal surfaces by SIgA is crucial to the process of protection and homoeostasis.

In addition to canonical immune exclusion, SIgA is endowed with the capacity to transport immune complexes via M‐cells to underlying dendritic cells, thus inducing attenuated mucosal and systemic immune responses.

Communication between natural polyreactive SIgA‐commensal bacteria complexes and the epithelial cells lining mucosal surfaces contributes to regulate the symbiotic host–commensal relationship.

SC, by itself, via multiple glycosylation sites, displays neutralising properties against pathogen‐associated molecules. This holds true when SC is bound to polymeric IgA in the SIgA molecule.

Increasing knowledge of the multiple modes of action of SIgA provides opportunities to investigate the potential of the antibody in passive immunisation against bacteria, viruses and toxins in the clinics.
Molecular Genetics of Chediak–Higashi Syndrome
Authors: Kaplan Jerry , Ward Diane M
Published: September 2013

Chediak–Higashi syndrome (CHS) is an autosomal recessive disorder associated with the formation of enlarged lysosomes and lysosome‐related organelles (LROs) clustered near the perinuclear region of cells. Affected vesicles include lysosomes, cytolytic granules, melanosomes and platelet dense granules. The enlarged vesicles give rise to decreased bacterial killing, partial albinism, defective wound repair, impaired coagulation and neurological problems. Patients succumb to untreated recurrent bacterial infections or a lymphoma‐like infiltration into the major organs of the body. Treatment for the disorder is prophylactic antibiotics followed by bone marrow transplant although pigmentation and neurological problems persist. The mutant gene, termedLyst, responsible for CHS is present in all eukaryotes and model organisms have been utilised to try to determine the function of Lyst. The biochemical function of Lyst has not been resolved but Lyst has been proposed to be involved in regulating lysosome/LRO size by either controlling vesicle fusion or fission.

Key Concepts:

Chediak–Higashi syndrome (CHS) is a lethal disorder with patients succumbing to pathogen infections if not treated with antibiotics.

CHS patients show multiorgan dysfunction due to enlarged lysosome‐related organelles in all cells of the body.

Treatment for CHS is bone marrow transplant, although neurological problems remain.

The mutant gene responsible for CHS is Lyst, a highly conserved gene present in all eukaryotes.

Lyst is a member of a family of proteins, BEACH, involved in vesicle trafficking.

Regulating lysosome/LRO size is important for normal cellular processes including pigmentation, coagulation, wound repair and immune function.
Analysis of Somatic Mutations in Cancer Tissues Challenges the Somatic Mutation Theory of Cancer
Authors: Satgé Daniel
Published: September 2013

According to the somatic mutation theory (SMT) of cancer, somatic mutations observed in cancerous tissues directly cause malignancy. However, a close look at the experimental data and observations about human diseases show many discrepancies with the theory, including the lack of specificity of the so‐called ‘cancer genes’ that are mutated in noncancerous tissues, and not mutated in cancers; the rarity of malignancies in some genetic conditions withdeoxyribonucleic acidrepair anomalies and the high number of initial mutations in early carcinogenesis. Above all, abnormal proliferations and altered tissue architecture before specific genetic anomalies are detected strongly support the idea that the correlation between carcinogenesis and genetic modifications is more complex and probably less determining than has been theorised by the SMT. Other theories that take into account tissue architecture and microenvironment, such as the tissue organisation field theory, are promising paths towards an understanding of oncogenesis.

Key Concepts:

Initial somatic mutations are found in cancer tissues much more frequently than expected from a random event.

Proliferative and architectural anomalies are observed in organs before genetic anomalies occur.

Mutations of the so‐called ‘cancer genes’ are present in noncancerous tissues.

Mutations of so‐called ‘cancer genes’ are not present in all cells of a cancer/tumour.

Tissues maintain their respective phenotypes despite many mutations.

Some conditions with DNA repair deficiency have no increased risk of cancer, and some others appear to be protected against particular cancer types.

Cancers can be induced by transplanting a normal tissue into an unusual environment for that tissue.

Cancer cells can be reverted to normal cells when implanted into a microenvironment that is normal for this type of cells.
An Overview of Cytokine Regulation of Inflammation and Immunity
Authors: Meager Anthony , Wadhwa Meenu
Published: September 2013

The defence of an organism depends on the recognition of harmful stimuli followed by appropriate activation of innate and adaptive immune responses. Primary recognition of harmful stimuli is mediated by specific receptors of monocytes, macrophages and dendritic cells, leading to cytokine production. Several cytokines have proinflammatory actions that drive the innate immune response, cause inflammation and activate adaptive immune responses. Further activation of adaptive immunity depends on cytokine regulation of T‐cell differentiation into specific T‐cell subsets with specific roles in defence against the invading pathogens. Although cytokine regulation of inflammation and immunity is crucial for protection against infection and injury, their actions in excess are associated with a variety of autoinflammatory and autoimmune diseases.

Key Concepts:

Cytokines are a broad class of biologically active proteins with hormone‐like actions that are produced in response to homoeostatic, and more particularly harmful, stimuli.

The extent of cytokine production is dependent both on the nature of the stimulus and on regulatory intracellular mechanisms.

Cytokines may act on any cells that bear receptors, by which, with the involvement of signal transduction pathways, nuclear gene transcription is activated.

Many cytokines act on cells of the immune and vascular systems to regulate cell proliferation, differentiation and activation of pro‐ or anti‐inflammatory mechanisms.

Monocytes, macrophages and dendritic cells bear ‘pattern recognition receptors’ and are especially sensitive to harmful stimuli such as pathogens bearing ‘pathogen‐associated molecular patterns (PAMPs)’.

Monocytes and macrophages produce the proinflammatory cytokines, for example, interleukin‐1, tumour necrosis factor‐α, responsible for inflammatory reactions and innate immune responses.

Cytokines such as interleukin‐12, interleukin‐18 and interleukin‐23 couple the innate immune response to adaptive immune responses mediated by T cells, B cells and natural killer cells.

T‐cell differentiation into specific T‐cell subsets is governed by several cytokines, for example, interleukin‐4 and interferon‐gamma, acting antagonistically to one another.

Excessive cytokine production or action leads to acute or chronic inflammation, which may trigger autoinflammatory and autoimmune diseases in the long term.
Molecular Genetics of Skeletal Muscle Channelopathies
Authors: Durran Siobhan CM , Matthews Emma , Hanna Michael
Published: September 2013

The skeletal muscle channelopathies are disorders of muscle excitability due to disruption of the normal functioning of skeletal muscle ion channels. Such disruption to excitability can manifest clinically as episodic muscle weakness or myotonia resulting in a number of disorders classified as periodic paralysis and nondystrophic myotonias. Significant overlap is observed between these disorders in terms of both symptoms and causative genes. More than 200 mutations have been identified overall within the skeletal muscle voltage‐gated ion channel genes, with the main causative genes including
CLCN‐1
,
SCN4A
and
CACNA1S
. However, ∼20% of patients have no genetic diagnosis despite a strong phenotype. Genetic research and functional analysis of mutations together have advanced our understanding of molecular disease mechanism as well as providing new insights into normal ion channel function.

Key Concepts:

Voltage‐gated ion channels are transmembrane proteins which selectively conduct ions across the plasma membrane on activation through a change in the membrane potential.

Skeletal muscle channelopathies are caused by mutations located in functionally important areas of voltage‐gated ion channels.

Symptoms manifest as intermittent alterations of skeletal muscle function.

A number of different ion channels are known to cause the same disorders resulting in genetic heterogeneity.

Mutations in the ion channels result in disruption of the sarcolemma membrane potential, which can cause myotonia through increased excitability or periodic paralysis due to decrease excitability.

Symptoms of myotonia can be the result of mutations in either
CLCN‐1
or
SCN4A
, whereas periodic paralysis is caused by mutations in
CACNA1S
,
SCN4A
,
KCNJ2
or
KCNJ18
.

Phenotypic variability is seen even amongst patients within a single family.

Significant symptom overlap occurs between disorders, which can lead to diagnostic confusion.
Molecular Genetics of Nasopharyngeal Carcinoma
Authors: Lun Samantha Wei‐Man , Cheung Chartia Ching‐Mei , Chow Chit , Chung Grace Tin‐Yun , Lo Kwok‐Wai
Published: September 2013

Nasopharyngeal carcinoma (NPC) is a distinctive type of squamous cell carcinoma of the head and neck region with remarkable ethnic and geographic distribution. It is consistently associated with Epstein–Barr virus (EBV) infection and serves as a fascinating model to understand the complex interaction among environmental, viral, and genetic factors in human tumourigenesis. The development of NPC involves clonal expansion of EBV‐infected cells and cumulative genetic and epigenetic changes. Both viral and cellular genes contribute to disease pathogenesis and their interplay creates distinct phenotypes, unique molecular features and tumour microenvironment. Recent findings on EBV‐encoded and cellular miRNAs demonstrate their importance in NPC progression by altering multiple cellular pathways. On the basis of current knowledge, we proposed a stepwise model describing the initiation events and the role of EBV latent infection and multiple genetic changes in NPC tumourigenesis.

Key Concepts:

Nonkeratinising NPC is consistently associated with EBV infection.

The development of NPC involves EBV latent infection and cumulative genetic and epigenetic changes influenced by predisposing genetic factors and environmental carcinogens.

Inactivation of tumour suppressor genes at chromosomes 3p and 9p and clonal expansion of EBV‐infected cells are critical initiation events in NPC tumourigenesis.

EBV‐encoded and cellular miRNAs contribute to the NPC progression by altering multiple cellular pathways and modulating EBV latent gene expression.

The interplay between viral and cellular genes contributes to the establishment of distinct phenotypes, unique molecular features and tumour microenvironment of NPC.
Reconstruction of the Ancestral Xenarthran Karyotype
Authors: Svartman Marta
Published: September 2013

Xenarthra is the group of mammals that reunites anteaters, armadillos and sloths. According to the most recent phylogenetic schemes, Xenarthra is considered one of the four main supraordinal eutherian clades. This group, found in Central and South America, is considered especially important as it may be at the base of the eutherian tree. Although most cytogenetic studies in Xenarthra have been restricted to a few specimens and poor resolution techniques, recent chromosome painting analyses in some Xenarthra species resulted in important data regarding mammalian karyotypic evolution. An ancestral karyotype with 2n=48 chromosomes has been recently proposed as ancestral to all Xenarthra. This complement is very similar to the 2n=46 proposed as ancestral to all eutherian mammals, which may be a further indication of the basal phylogenetic position of Xenarthra in the eutherian tree.

Key Concepts:

Xenarthra is a Central and South American group of mammals represented by anteaters, armadillos and sloths.

Xenarthra is phylogenetically important because of its likely basal position in the tree of eutherian mammals.

In general, cytogenetic data on Xenarthra are restricted to a few specimens and to low resolution techniques.

However, the recent use of molecular cytogenetics, namely chromosome painting, in Xenarthra has provided data that allowed the reconstruction of a hypothetical Xenarthra ancestral karyotype (XAK) with 2n=48.

The 2n=48 XAK closely resembles the proposed ancestral eutherian karyotype (AEK) with 2n=46, which further supports the idea that Xenarthra is basal to all eutherians.
Molecular Genetic Causes of Discordance in Monozygotic Twins
Authors: Czyz Witold , Ramagopalan Sreeram V
Published: September 2013

Although monozygotic (MZ) twins arise from the same gametes and a single zygote, they can at times reveal molecular genetic discordance. Differences in ploidy, chromosomal rearrangements and structural anomalies as well as different copy number variations (CNVs), point mutation discordance and genetic mosaicism have all been documented in MZ siblings. Depending on the type and magnitude, genetic discordance may lead to markedly different phenotypes. Traditionally, the best‐evidenced type of discordance encompasses a range of chromosomal abnormalities, partly due to their significant multiple effects on a phenotype. In contrast, surveying for single nucleotide polymorphism and CNV discordance globally poses more challenges. In the recent decades, growing evidence for low‐level CNV and point mutation discordance as well as mosaicism has amassed, although their frequency and phenotypic significance are yet to be established. High‐throughput sequencing strategies are likely to provide answers.

Key Concepts:

Despite stemming from the same zygote, monozygotic twins may develop genetic discordance.

Postzygotic genetic alterations often result in genetic mosaicism in one or both of the twins.

Confirmed genetic discordance in MZ twins encompasses mainly known disorders with clear or multiple/global effects, including five extremely rare cases of point mutations responsible for monogenic disorders and a range of chromosomal abnormalities as well as a few cases of trinucleotide repeat disorder discordance.

The most common type of genetic discordance in MZ twins are aneuploidies, particularly 45,X0 monosomy and, to a lesser degree, trisomies 21, 15 and 13, whereas discordance for structural rearrangements is even less frequent.

In MZ twins affected by aneuploidies, somatic mosaicism often plays a critical role in phenotypic discordance.

Genome‐wide studies of SNP and CNV discordance in twins face technical difficulties and have not yet brought a definite answer, although there is limited evidence for very low‐level discordance.

It will be challenging to fully ascertain the magnitude of genetic discordance in twins due to possible small‐scale SNP and CNV mosaicism across different tissues.
Genetics of Depression
Authors: Hodgson Karen , McGuffin Peter
Published: September 2013

Probing the genetic basis of depression not only informs our understanding of the role that genes play in disease, but also further offers the potential to provide invaluable insights into the aetiology, classification and neurobiology of the disorder. Moreover, understanding the genetics of depression may offer a starting point for the development of novel, and potentially more efficacious treatments for patients.

Although a number of genes have been implicated in depression, a genetic variant that is unequivocally associated with an increased risk of the disease is yet to be identified. As genome‐wide approaches to analysing genetic variation gain momentum, large‐scale collaborations have brought insights into how best to conceptualise depression as an illness. Nonetheless, the identification of specific genetic variants associated with depression still eludes researchers. By building on the knowledge gained from these collaborative datasets, and utilising newer and more sophisticated technologies and methodologies, it is likely that researchers will be able to replicate in depression, the successes of genetic research in other complex disorders.

Key Concepts:

MDD is a complex genetic disorder involving interactions between multiple genetic variants and environmental factors.

Some areas of interest have been implicated via linkage methodologies in MDD, but this method is more suited to more strongly heritable forms of the disease.

Many candidate gene studies of MDD have been underpowered to detect small genetic influences, and are constrained by our limited understanding of the neurobiology of the disease.

Genome‐wide association methodologies have not yet identified any clear markers of the disease, but have informed our understanding of MDD.

Following the progress of genetic research into other disease phenotypes, the collection of larger patient cohorts is likely to yield success in identifying the genetic variants involved in MDD.

Newer technologies and analysis methods to model the biological complexity of the illness are also rapidly evolving.
Weiss, Paul Alfred
Authors: Brauckmann Sabine
Published: September 2013

Paul A. Weiss (1898–1989), born and educated in Vienna (Austria), first studied the movements of butterfly wings. He argued that the locomotion patterns arrange a network system of behaviour, which controls as a whole the future movements. By transplantation and tissue culture experiments he studied the issue as to how motor nerves succeed in moving the correspondent muscle. The data he explicated with the resonance principle, stating that the nerve and the muscle are attuned to each other by electroacoustic signals. Until 1950, he discovered the axonal transport of peripheral nerves and invented a new surgical technique to bridge cut nerves without sutures. In developmental biology, he explained the mechanisms of cell contact and investigated the self‐sorting of embryonic cells, a precursor of modern stem cell research. In 1960, Weiss and his collaborators produced a media event when demonstrating that cell suspensions have the ability to reconstitute complete body organs. Further, they improved the experimental tools of phase contrast microscopy, time‐lapse motion films and tissue cultivation. Weiss' experimental work had a strong impact on the progress of developmental, cell and neurobiology in the twentieth century, and influenced the newly forming disciplines of cell biology and the neurosciences.

Key Concepts:

The concept of contact guidance improved Cajal's doctrine of neurotropism.

Experimental data demonstrated axonal flow in the 1940s, but were not accepted until the 1960s.

Experiments on cell sorting and cell suspensions are precursors of modern stem cell research.

The disciplination of the neurosciences was delayed by the resistance of (medical) neurophysiology.

Prematurity prevents the acceptance of experimental data, regardless of being correct.
Astro‐medicine
Authors: Nutton Vivian
Published: September 2013

Astromedicine, the notion that human health is in some way linked to the stars, is found in many societies. The Babylonians and Ancient Egyptians were famous for their astronomical knowledge, and used it to predict and diagnose disease, and influenced some Greek and Roman doctors from 100 BCE onwards. Galen of Pergamum preferred a meteorological explanation for illness, but his discussion of critical days allowed his successors in Late Antiquity to include the influence of the stars in their calculations. This Galenic astromedicine was developed by the Arabs and taken over in the learned medicine of Western Europe from 1200 CE. Objections were raised in the Renaissance, and by 1600, medical astrology had fallen out of favour among the elite physicians. Patients, however, still flocked to astrologers like Simon Forman. Arabic astromedicine also spread eastwards to India and Tibet, although Chinese astromedicine developed differently.

Key Concepts:

Astromedicine has been widely practised for centuries in many societies.

From Egypt and Babylonia predicting diseases by the stars entered Greek medicine around 250 BCE.

Astromedicine achieved respectability in Late Antiquity, and was further developed in the Islamic world.

From the Islamic world astromedicine passed to Western Europe as part of the new university medical education.

The Renaissance humanist doctors strongly attacked astromedicine, which by 1650 was seen as dubious quackery, even if many patients believed in it.

Indian and particularly Chinese medicine included astromedicine as a significant part of their continuing medical traditions.
Evolution of Sex Chromosomes in Plants
Authors: Charlesworth Deborah
Published: September 2013

Sex chromosomes are known from a minority of flowering plants (angiosperms), and from some haploid plants, but the sex‐determining chromosomes of many dioecious plants (i.e. species with the sexual stage individuals being either purely male or female) are either unstudied, or are not morphologically different between the two sexes. Both these observations and the taxonomically scattered distribution of species with sex chromosomes suggest that many plant sex chromosome systems evolved recently and independently in different taxa. A fundamental characteristic of sex chromosome pairs is possession of a nonrecombining region. Some plants may be in an early stage of evolving separate sexes, so that this has not yet evolved. Other plants appear to have small nonrecombining regions, or ‘proto‐sex chromosomes’, whereas a few species have cytologically detectable sex chromosome heteromorphism, and probably have large nonrecombining regions. With modern molecular approaches, these different states can now be identified and studied.

Key Concepts:

The evolution of separate sexes (males and females) from an initial state in which individuals have both sex functions requires mutations of at least two genes.

Sex chromosome pairs are defined as homologous chromosomes (that pair in meiosis, and part of the pair recombines) but which also include a nonrecombining region involved in sex determination.

During the evolution of separate sexes, after male‐ and female‐sterility mutations arise, selection will promote reduced recombination between the different genes, in order to avoid producing sterile individuals (with both male‐ and female‐sterility mutations) that will arise through recombination between the genes.

The existence of evolutionary strata (see Glossary) shows that recombination suppression between sex chromosomes has occurred in several distinct events, at different times, and the main hypothesis to explain this is that sexually antagonistic polymorphisms may arise in the recombining regions of sex chromosome pairs, and that this situation again generates selection for reduced recombination.
Phylogenetic Hypothesis Testing
Authors: Irisarri Iker , Zardoya Rafael
Published: September 2013

Probabilistic methods of phylogenetic reconstruction (maximum likelihood and Bayesian inference) provide a robust framework for the statistical inference of phylogenies and for phylogenetic hypothesis testing. The likelihood ratio test is a powerful statistical tool for comparing the explanatory power of alternative phylogenetic hypotheses that strongly relies on the likelihood function. In the Bayesian framework, phylogenetic hypothesis testing is usually performed using Bayes' factors. Statistical tests involving phylogenies are widely used for comparing alternative phylogenetic hypotheses (tree topologies), studying evolutionary rate constancy (clock‐like behaviour) ofdeoxyribonucleic acid(DNA) and protein sequences, estimating changes in selective pressures at the sequence level, inferring ancestral character states at internal nodes on phylogenies, estimating historical biogeography, examining patterns of trait evolution along the tree or applying phylogenetic comparative methods, among others. In addition, molecular dating analyses allow formulating and comparing hypotheses on absolute divergence times of cladogenetic events.

Key Concepts:

Probabilistic methods of phylogeny reconstruction rely on explicit models of evolution, and provide a powerful framework for testing evolutionary hypotheses.

The likelihood principle provides a direct approach to hypothesis testing in terms of probability.

The likelihood ratio test is a powerful tool for comparing two alternative hypotheses.

In the Bayesian framework, hypotheses are usually compared using Bayes' factors.

Topology tests evaluate whether the analysed data, besides supporting a particular phylogenetic hypothesis, could support or reject alternative tree topologies.

Molecular dating analyses, by converting evolutionary distances into absolute ages, allow comparing alternative scenarios of temporal divergence on phylogenetic trees.

The effect of natural selection can be detected by measuring the relative rates of synonymous and nonsynonymous substitutions in multiple nucleotide sequence alignments of protein‐coding genes.

Explicit models of trait evolution support probabilistic reconstructions of ancestral character states at internal nodes on phylogenies and testing of hypotheses regarding the process of trait evolution.

Phylogenetic comparative methods aim to identify adaptation through correlations between species traits and other variables, while accounting for phylogenetic nonindependence of data.
Automated Continuous Online Monitoring of Polymerization Reactions (ACOMP) and Related Techniques
Authors: Reed Wayne F.
Published: September 2013

Automatic continuous online monitoring of polymerization (ACOMP) is a widely applicable platform for monitoring and potentially controlling polymerization reactions. It relies on the continuous extraction, dilution, and conditioning of a small sample stream from the reactor on which measurements by various combinations of detectors are made. By combining simultaneous data from multiple detectors, continuous monitoring of salient reaction characteristics can be made, such as kinetics, conversion of comonomers, composition drift, evolution of molecular mass and intrinsic viscosity, and detection of unusual phenomena, such as microgelation and runaway reactions. Typical detectors include light scattering,UV/visible spectrophotometry, viscometry, refractivity, and polarimetry. Recent additions toACOMPinclude the ability to use multiple similar sensors to detect the onset and evolution of polymer‐stimuli‐responsive behavior during synthesis, for example, copolymer compositions at which a lower critical solution temperature occurs.ACOMPhas been applied to free radical, controlled free radical, and condensation reactions, to micellar, emulsion, and inverse emulsion polymerization, to postpolymerization and derivitization reactions, and to batch, semibatch, and continuous reactors. WhileACOMPis not inherently a chromatographic method, its continuous stream can be used in automatic conjunction with gel permeation chromatography (GPC) and other separation chromatographies. A growing area forACOMPis its integration into predictive and closed‐loop reaction control.
Fundamentals and Advances of Orbitrap Mass Spectrometry
Authors: Scigelova Michaela , Makarov Alexander
Published: September 2013

Analytical chemistry has considerably benefited from the developments in the field of mass spectrometry. The high resolution, mass accuracy, and sensitivity offered by modern mass spectrometers have been essential in addressing analytical needs in numerous areas of research as well as in routine laboratory praxis. The most recent addition to the family of mass spectrometers has been the Orbitrap analyzer, making an ultrahigh‐resolution mass spectrometry accessible to most life science laboratories. The Orbitrap‐based instrumentation has established itself firmly in the field of proteomics, metabolomics, and metabolite analysis. Moreover, it is gaining increased popularity also in areas of bioanalysis, lipidomics, doping, as well as in drug and pesticide residue analysis. This article presents the principle of operation of the Orbitrap analyzer, its most recent technological developments, and outlook, and it reviews application areas where the Orbitrap analyzers represent the state‐of‐the‐art solution to a multitude of analytical needs.
Neutron Scattering Spectroscopy
Authors: Parker Stewart F.
Published: September 2013

Neutron vibrational spectroscopy (inelastic neutron scattering (INS)) is a form of vibrational spectroscopy that is complementary to infrared and Raman spectroscopies. It has a very wide spectral range of zero to several thousand wavenumbers; there are no selection rules, so all modes are allowed and comparison with ab initio calculations is straightforward. The disadvantages are that it is relatively insensitive and restricted to the solid state. It is particularly sensitive to modes involving hydrogen, and in hydrogenous materials, these dominate the spectra. In this article, the history, theory, and practice of the technique are briefly reviewed. The extensive range of applications of this form of spectroscopy is illustrated with examples in the areas of hydrogen storage, catalysis, soft condensed matter, ice, carbons, and magnetism.
Soil: Forensic Analysis
Authors: Fitzpatrick Robert W.
Published: September 2013

Earth materials such as soils, rocks, minerals, and particles from man‐made materials such as bricks provide excellent evidence to link criminals to crime scenes. Forensic soil scientists are also using advanced automated techniques, which have the ability to acquire information from smaller samples to make soil forensics an increasingly popular tool in criminal investigations. The aim of soil forensic analysis is to associate soil, rock, or mineral samples taken from an item, such as shoes, clothing, shovel, or vehicle with a specific location. Soil materials are powerful, perhaps ideal, pieces of contact trace evidence to help in criminal investigations.

Soil forensic investigations usually involve collection of one or more soil samples followed by soil characterization. Collected samples are categorized as (i)
questioned soil samples
whose origin is unknown or disputed (suspect or victim), (ii)
control soil samples
whose origin is known (crime scene), and (iii)
alibi soil samples
whose origin is known and that provide a measure of the distinctiveness of the questioned and control samples. Soil characterization often requires the following four‐stage approach, which combines descriptive, analytical, and spatial information: (i) Initial characterization for screening of samples involving morphological descriptions. (ii) Semi‐detailed characterization involving semi‐quantification of minerals and organic matter following sample selection and size fractionation (<50 µm). (iii) Detailed characterization and quantification of minerals and organic matter using additional analytical techniques and/or methods of sample preparation, separation, or concentration such as size or magnetic or heavy mineral fractionation. (iv) Integration and extrapolation of soil information from one scale to the next, to build a coherent model of soil information from microscopic observations to the landscape scale, which often involves soil/geological maps and geophysics. Progression of a soil forensic examination through each of the four stages will depend on the amount of sample available and the results from the early stages of the examination. The significance and relevance of established concepts and standard terminologies used in soil science and geology with practical relevance to forensic science are emphasized.
Fully probabilistic seismic displacement analysis of spatially distributed slopes using spatially correlated vector intensity measures
Authors: Du Wenqi , Wang Gang
Published: September 2013

Earthquake‐induced slope displacement is an important parameter for safety evaluation and earthquake design of slope systems. Traditional probabilistic seismic hazard analysis usually focuses on evaluating slope displacement at a particular location, and it is not suitable for spatially distributed slopes over a large region. This study proposes a computationally efficient framework for fully probabilistic seismic displacement analysis of spatially distributed slope systems using spatially correlated vector intensity measures (IMs). First, a spatial cross‐correlation model for three key ground motion IMs, that is, peak ground acceleration (PGA), Arias intensity, and peak ground velocity, is developed using 2686 ground motion recordings from 11 recent earthquakes. To reduce the computational cost, Monte Carlo simulation and data reduction techniques are utilized to generate spatially correlated random fields for the vector IMs. The slope displacement hazards over the region are further quantified using empirical predictive equations. Finally, an illustrative example is presented to highlight the importance of the spatial correlation and the advantage of using spatially correlated vector IMs in seismic hazard analysis of spatially distributed slopes. Copyright © 2013 John Wiley & Sons, Ltd.
PUBLIC ADMINISTRATION IN A GLOBALIZED ASIA: INTELLECTUAL IDENTITIES, CHALLENGES, AND PROSPECTS
Authors: Haque M. Shamsul
Published: September 2013

In most Asian countries, the domain of public administration continues to bear the legacy of colonial rule and postcolonial modernization led by Western nations. It remains crucial to highlight this exogenous formation of administrative systems in this age of globalized New Public Management. Such imposed or borrowed Western models of administrative practices have often been ineffective because of their incompatibility with the indigenous Asian contexts, and they led to the worsening society–administration gaps and pathological outcomes. Beyond the continuing Western (especially American) intellectual hegemony in the field's knowledge‐building, the prominent Asian scholars themselves have been educated mostly in foreign universities and institutions, which is not conducive to the construction of indigenous administrative knowledge based on an Asian perspective. In this context, it is imperative to explore the displacement of pre‐colonial administrative traditions by colonial and postcolonial interventions, to examine how the contemporary administrative systems in Asia are based on exogenous models, and to assess the feasibility of constructing an overarching intellectual perspective that could be claimed as Asian public administration. This article attempts to explore these intellectual concerns with specific reference to selected cases in East, South, and Southeast Asia. Copyright © 2013 John Wiley & Sons, Ltd.
BRAFV600E Mutation Analysis in Papillary Thyroid Carcinoma: Is it Useful for all Patients?
Authors: Ito Yasuhiro , Yoshida Hiroshi , Kihara Minoru , Kobayashi Kaoru , Miya Akihiro , Miyauchi Akira
Published: September 2013

Background

The BRAFV600E mutation has been adopted as a prognostic factor in papillary thyroid carcinoma (PTC). However, it remains unclear whether routine BRAF mutation analysis is useful in establishing a prognosis for PTC patients. In the present study we investigated BRAF mutation analysis in a large number of PTC patients with long‐term follow‐up.

Patients and methods

We enrolled 766 patients from our hospital who underwent initial surgery for PTC without distant metastasis at diagnosis between 1996 and 2001, and whose BRAF mutation of primary lesions could be analyzed. The average age and follow‐up period were 51 years and 130 months, respectively.

Results

To date, 77 (10 %) and 37 (5 %) patients have developed lymph node and distant recurrence, respectively, and 10 (1 %) have died of PTC. The BRAF mutation was positive in 281 patients (37 %), and it had no prognostic impact on lymph node recurrence‐free (LNRFS) (p = 0.700), distant recurrence‐free (DRFS) (p = 0.696), and cause‐specific (CSS) (p = 0.125) survival in our entire series. However, CSS of BRAF mutation‐positive high‐risk patients based on AMES (p = 0.030), MACIS (score >6) (p = 0.017), the UICC stage (IVa) (p = 0.021), CIH classification (Sugitani et al. Surgery 135:139–148, 2004) (p = 0.015), and our own classification system (Ito et al. World J Surg 34:2570–2580, 2010) (p = 0.010) were significantly poorer than CSS of mutation‐negative high‐risk patients. The BFAF mutation did not affect CSS of non‐high‐risk patients, although the incidence of the BRAF mutation did not significantly differ between high‐risk and non‐high‐risk groups based on these classification systems. The BRAF mutation was not related to LNRFS and DRFS in the subsets of high‐risk and non‐high‐risk patients.

Conclusions

BRAF mutation analysis is useful in estimating the CSS of high‐risk PTC patients based on the representative classification systems. It was not related to the prognosis in non‐high‐risk patients, at least those living in Japan.
Szenario-Planung als Instrument einer „klimawandelangepassten“ Stadt- und Regionalplanung – Bausteine der zukünftigen Flächenentwicklung und Szenarienkonstruktion im Stadt-Umland-Raum Rostock
Authors: Hagemeier-Klose Maria , Albers Meike , Richter Michael , Deppisch Sonja
Published: September 2013

Climate change and its impacts form a new major challenge for spatial planning, as planning still shall guarantee a sustainable development in the face of complexity and uncertainty. The presented scenario planning process in the urban region of Rostock, Germany aims at adaptation to the impacts of climate change and herby realizes intensive stakeholder participation. Scenarios are elaborated on the basis of the analysis of key factors for the future spatial development stemming from different thematic fields such as society, ecology, economics and policy and on the basis of the analysis of potential climate change impacts. These scenarios combine impacts of different severity with different potential developments of the key factors to a range of differentiated pictures of the potential future of the urban region. The scenarios allow spatial planners to consider a range of potential futures as well as interrelationships among the key factors and between the key factors and the climate change impacts. As such, they offer the possibility to cope with the main challenges of climate change, complexity and uncertainty and to integrate these challenges into a stakeholder dialogue. This was evaluated to be an innovative and sense making method, which is until now hardly implemented into current planning practice. The scenarios serve as basis for the formulation of concrete adaptation strategies and measures. Moreover, the initiated stakeholder dialogue can later facilitate the practical implementation of developed measures.
Anti‐Inflammatory and Anti‐Oxidative Nutrition in Hypoalbuminemic Dialysis Patients (AIONID) study: results of the pilot‐feasibility, double‐blind, randomized, placebo‐controlled trial
Authors: Rattanasompattikul Manoch , Molnar Miklos Z. , Lee Martin L. , Dukkipati Ramanath , Bross Rachelle , Jing Jennie , Kim Youngmee , Voss Anne C. , Benner Debbie , Feroze Usama , MacDougall Iain C. , Tayek John A. , Norris Keith C. , Kopple Joel D. , Unruh Mark , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar
Published: September 2013

Background

Low serum albumin is common and associated with protein‐energy wasting, inflammation, and poor outcomes in maintenance hemodialysis (MHD) patients. We hypothesized that in‐center (in dialysis clinic) provision of high‐protein oral nutrition supplements (ONS) tailored for MHD patients combined with anti‐oxidants and anti‐inflammatory ingredients with or without an anti‐inflammatory appetite stimulator (pentoxifylline, PTX) is well tolerated and can improve serum albumin concentration.

Methods

Between January 2008 and June 2010, 84 adult hypoalbuminemic (albumin <4.0 g/dL) MHD outpatients were double‐blindly randomized to receive 16 weeks of interventions including ONS, PTX, ONS with PTX, or placebos. Nutritional and inflammatory markers were compared between the four groups.

Results

Out of 84 subjects (mean ± SD; age, 59 ± 12 years; vintage, 34 ± 34 months), 32 % were Blacks, 54 % females, and 68 % diabetics. ONS, PTX, ONS plus PTX, and placebo were associated with an average change in serum albumin of +0.21 (P = 0.004), +0.14 (P = 0.008), +0.18 (P = 0.001), and +0.03 g/dL (P = 0.59), respectively. No related serious adverse events were observed. In a predetermined intention‐to‐treat regression analysis modeling post‐trial serum albumin as a function of pre‐trial albumin and the three different interventions (ref = placebo), only ONS without PTX was associated with a significant albumin rise (+0.17 ± 0.07 g/dL, P = 0.018).

Conclusions

In this pilot‐feasibility, 2 × 2 factorial, placebo‐controlled trial, daily intake of a CKD‐specific high‐protein ONS with anti‐inflammatory and anti‐oxidative ingredients for up to 16 weeks was well tolerated and associated with slight but significant increase in serum albumin levels. Larger long‐term controlled trials to examine hard outcomes are indicated.

Electronic supplementary material

The online version of this article (doi:10.1007/s13539‐013‐0115‐9) contains supplementary material.
Optical manipulation of Saccharomyces cerevisiae cells reveals that green light protection against UV irradiation is favored by low Ca2+ and requires intact UPR pathway
Authors: Farcasanu Ileana C. , Mitrica Radu , Cristache Ligia , Nicolau Ioana , Ruta Lavinia L. , Paslaru Liliana , Comorosan Sorin
Published: September 2013

Optical manipulation of Saccharomyces cerevisiae cells with high density green photons conferred protection against the deleterious effects of UV radiation. Combining chemical screening with UV irradiation of yeast cells, it was noted that the high density green photons relied on the presence of intact unfolded protein response (UPR) pathway to exert their protective effect and that the low Ca2+ conditions boosted the effect. UPR chemical inducers tunicamycin, dithiotreitol and calcium chelators augmented the green light effect in a synergic action against UV‐induced damage. Photo‐manipulation of cells was a critical factor since the maximum protection was achieved only when cells were pre‐exposed to green light.
Discovery of cellobionic acid phosphorylase in cellulolytic bacteria and fungi
Authors: Nihira Takanori , Saito Yuka , Nishimoto Mamoru , Kitaoka Motomitsu , Igarashi Kiyohiko , Ohtsubo Ken‧ichi , Nakai Hiroyuki
Published: September 2013

A novel phosphorylase was characterized as new member of glycoside hydrolase family 94 from the cellulolytic bacterium Xanthomonas campestris and the fungus Neurospora crassa. The enzyme catalyzed reversible phosphorolysis of cellobionic acid. We propose 4‐O‐β‐d‐glucopyranosyl‐d‐gluconic acid: phosphate α‐d‐glucosyltransferase as the systematic name and cellobionic acid phosphorylase as the short names for the novel enzyme. Several cellulolytic fungi of the phylum Ascomycota also possess homologous proteins. We, therefore, suggest that the enzyme plays a crucial role in cellulose degradation where cellobionic acid as oxidized cellulolytic product is converted into α‐d‐glucose 1‐phosphate and d‐gluconic acid to enter glycolysis and the pentose phosphate pathway, respectively.
Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats
Authors: Cohen Ori S. , Varlinskaya Elena I. , Wilson Carey A. , Glatt Stephen J. , Mooney Sandra M.
Published: September 2013

Prenatal exposure to moderate doses of valproic acid (VPA) produces brainstem abnormalities, while higher doses of this teratogen elicit social deficits in the rat. In this pilot study, we examined effects of prenatal exposure to a moderate dose of VPA on behavior and on transcriptomic expression in three brain regions that mediate social behavior. Pregnant Long Evans rats were injected with 350 mg/kg VPA or saline on gestational day 13. A modified social interaction test was used to assess social behavior and social preference/avoidance during early and late adolescence and in adulthood. VPA‐exposed animals demonstrated more social investigation and play fighting than control animals. Social investigation, play fighting, and contact behavior also differed as a function of age; the frequency of these behaviors increased in late adolescence. Social preference and locomotor activity under social circumstances were unaffected by treatment or age. Thus, a moderate prenatal dose of VPA produces behavioral alterations that are substantially different from the outcomes that occur following exposure to a higher dose. At adulthood, VPA‐exposed subjects exhibited transcriptomic abnormalities in three brain regions: anterior amygdala, cerebellar vermis, and orbitofrontal cortex. A common feature among the proteins encoded by the dysregulated genes was their ability to be modulated by acetylation. Analysis of the expression of individual exons also revealed that genes involved in post‐translational modification and epigenetic regulation had particular isoforms that were ubiquitously dysregulated across brain regions. The vulnerability of these genes to the epigenetic effects of VPA may highlight potential mechanisms by which prenatal VPA exposure alters the development of social behavior.