bluuebunny/crossref_metadata_2025 huggingface dataset:
The V1 hypothesis—creating a bottom-up saliency map for preattentive selection and segmentation
Authors: Zhaoping Li
Published: August 2014

This chapter gives a full account of the theoretical development and experimental investigations of the hypothesis that the primary visual cortex (V1) creates a bottom-up saliency map to guide visual attention exogenously. The chapter details the background motivations, theoretical formulation, and experimental tests of the hypothesis, as well as a neural circuit model of the primary visual cortex for the underlying neural mechanisms. The hypothesis links two bodies of data: one is of physiological data on intracortical interactions in V1 and the consequent contextual influences in V1 neural responses; the other is of behavioral data on attention capture, visual search, and visual segmentation. In light of the saliency map in V1, the chapter additionally discusses the roles of the extrastriate visual cortices, contrasts the roles of the central and peripheral visual fields, and reflects on the dissociation between attention capture and perceptual awareness.
Models of nucleotide substitution
Authors: Yang Ziheng
Published: August 2014

This chapter discusses Markov chain models of nucleotide substitution, such as JC69, K80, HKY85 and the general time-reversible (GTR) model, and their use in the calculation of the distance between two DNA sequences. It also introduces the theory of continuous time Markov chains used to model molecular sequence evolution, as well as statistical inference methods such as maximum likelihood (ML) and likelihood ratio test (LRT).
Bayesian phylogenetics
Authors: Yang Ziheng
Published: August 2014

This chapter discusses the implementation of various models of genetic sequence evolution in Bayesian phylogenetic analysis. It discusses the specification of priors for parameters in such models, as well as proposals that change those parameters. The chapter provides an extensive discussion of various tree perturbation algorithms used as Markov chain Monte Carlo (MCMC) proposals (such as nearest neighbour interchange (NNI), subtree pruning and regrafting (SPR), tree bisection and reconnection (TBR), etc.), as well as strategies for generating branch lengths in the new proposed tree. Several strategies for deriving the proposal ratios in sophisticated moves are illustrated with examples. The issue of extremely high posterior probabilities for trees or clades is discussed.
Neutral and adaptive protein evolution
Authors: Yang Ziheng
Published: August 2014

This chapter introduces the major theories of molecular evolution, such as the neutral theory, the nearly neutral theory, and the selectionist theory. It discusses the major neutrality tests designed to test the neutral theory using population data. The bulk of the chapter discusses various Markov chain models of codon substitution and their use in detecting Darwinian selection driving the fast evolution of protein-coding genes, as indicated by accelerated nonsynonymous substitution rates. Branch models, site models, and branch-site models are all covered in detail. The chapter then discusses empirical findings in genome scans for positive selection: genes involved in host–pathogen antagonism or in male and female reproduction, as well as duplicated genes that have acquired new functions are most often found to be under Darwinian selection.
Simulating molecular evolution
Authors: Yang Ziheng
Published: August 2014

This chapter introduces computer simulation and in particular simulation of the molecular evolutionary process. It covers the generation of random numbers as well as other discrete and continuous random variables. The chapter then discusses the simulation of the Poisson process, the variable-rate Poisson process, and discrete-time and continuous-time Markov chains. Different strategies for simulating sequence alignments through molecular evolution are then discussed.
The diversity of sexual cycles
Authors: Beukeboom Leo W. , Perrin Nicolas
Published: August 2014

The sexual cycles of eukaryotes vary immensely in terms of the relative importance of the haploid and diploid phases, the differentiation between gametes, and the timing and mode of sex determination. The chapter discusses the evolutionary advantages of haploid and diploid phases, the conditions for the maintenance of haplo-diplontic cycles, and the role of disruptive selection in the evolution from isogamy to anisogamy and oogamy. The chapter proposes a typology for sexual cycles based on the relative importance of haploid and diploid phase, whether sex is determined at the haploid or diploid stage, and whether the initial trigger is genetic or epigenetic. The chapter develops the concepts of heterothallism versus homothallism, haplo- versus diplo-genotypic sex determination, dioicy versus dioecy, monoicy versus monoecy, self-incompatibility systems and secondary mating types. The chapter considers the diversity of epigenetic sex-determination systems (mating-type switching, simultaneous and sequential hermaphroditism, as well as environmental, social, maternal, or parasite control of sex determination) and discusses the ultimate and proximate causes favouring their evolution, as well as their likely role in transitions from haplo- to diplo-genotypic sex determination.The electronic addendum of this chapter (Section 2.2) describes in more detail the diversity and phylogenetic distribution of sex-determination types among extant eukaryotes.
Molecular mechanisms of sex determination
Authors: Beukeboom Leo W. , Perrin Nicolas
Published: August 2014

This chapter first describes the overall structure of sex-determination cascades and the function of the main upstream and downstream actors (Section 3.1). Given the fundamental bipotentiality of genomes, the mechanisms of sex determination must insure proper development towards one or the other sex, and not towards intermediate phenotypes of reduced fertility. This is achieved via antagonisms that inhibit alternative pathways, and feedback auto-regulatory loops, acting as memory devices that maintain sexual identity throughout life. Transitions in sex-determination pathways may occur at any step along the cascade, through neo- or sub-functionalization following gene duplication, changes in the hierarchical position or timing of gene expression, alterations of gene function, or changes in transcriptional and translational regulation of genes. Section 3.2 delineates the structure and functioning of MAT loci, and describes specific pathways of haploid mating-type determination in a few model systems, as well as the molecular mechanisms of mating-type switching and homothallism. Section 3.3 focuses on diploid sex determination in two contrasted systems. In angiosperms, where floral meristems are organized by MADS-box transcription factors, different genders evolve via the selective abortion of male or female organs, as exemplified in a few model systems. In contrast, genders in animals evolve via the development of undifferentiated gonads into either testes or ovaries. The crucial roles of DM-domain genes in all animals, Sox genes in vertebrates, and transformer genes in insects, are developed. Finally, Section 3.4 outlines the molecular mechanisms of self-incompatibility and induction types in some diplontic or sub-diplontic lineages.
The quantitative genetics of sex determination
Authors: Beukeboom Leo W. , Perrin Nicolas
Published: August 2014

This chapter approaches sex determination from a quantitative genetics perspective. Although inheritance of sexes is often Mendelian, sex is better described as a threshold trait, underlain by a liability factor that may have both genetic and environmental variance. Accordingly, sex genotypes are best described as reaction norms in the multi-dimensional space generated by environmental and liability factors. Genetic variance may stem from one multi-allelic locus or multiple loci. Environmental variance may stem from a diversity of social effects (e.g. density) or external conditions, of which temperature plays a prominent role. Mixed systems, with a mixture of genotypic and environmental effects on sex determination, seem widespread, running against the traditional dichotomous view that opposes GSD to ESD. Large heritability values for the pivotal temperature have been found in ‘ESD’ species, and many studies have revealed significant genotype × environment interactions for sex ratios. Selection experiments have triggered quick sex-ratio responses to selection, even in the presence of specialised sex chromosomes. Although several case studies have uncovered examples of local adaptation, the adaptive significance of genetic and environmental control over sex determination requires further study.
Evolutionary correlates of sex-determination systems
Authors: Beukeboom Leo W. , Perrin Nicolas
Published: August 2014

Sex-determination systems have profound consequences on the biology of organisms, affecting many aspects of their life histories. Certain sex-determination systems may affect the evolution of polyploidy and parthenogenesis. Sex allocation, the relative investment of resources to the male versus female function, bears direct link with sex determination; sex chromosomes play an important role in this context because they can constrain adaptive sex allocation, harbour meiotic drive elements, or protect against the invasion of cytoplasmic sex-ratio distorters. Sex chromosomes and patterns of heterogamety may also affect sexual selection: there is extensive theory about the evolution of sex linkage of sexually dimorphic traits, including sexually antagonistic genes, but more empirical evidence is required. Finally, sex-determination systems can interfere with reproductive isolation and speciation processes. Sex chromosomes largely contribute to the several ‘rules of speciation’ including Haldane’s rule (higher sensitivity of the heterogametic sex to hybridization), Darwin’s corollary (asymmetric hybrid sensitivity), and large X-effects (disproportionate effect of X chromosomes on hybrid sterility or unviability). These reciprocal interactions between sex-determination systems and processes of sexual selection and speciation are illustrated with specific examples.
The quantitative genetics of senescence in wild animals
Authors: Charmantier Anne , Brommer Jon E. , Nussey Daniel H.
Published: August 2014

There is now overwhelming empirical evidence for age-related declines in fitness-related traits, i.e. senescence, during adulthood in wild vertebrate populations, presumably underpinned by physiological deterioration. Longitudinal field studies are also demonstrating that the rates of these observed declines vary among individuals and among traits. From an evolutionary perspective, the challenge remains to determine the contribution of genetic sources to this variation and the genetic correlations among traits underpinning fitness at different ages in natural systems. Although laboratory studies are revealing an ever-increasing amount about potential genetic and physiological pathways regulating lifespan and ageing in model systems, quantitative genetic studies in the wild can provide unique insights into how selection has shaped and maintained variation in ageing trajectories and senescence under complex, natural conditions. This chapter briefly discusses the classical evolutionary theories of ageing, emphasising the importance of estimating age-dependent patterns of genetic (co)variance (genotype-by-age interactions; G × A), rather than attempting to disentangle non-mutually exclusive putative mechanisms such as mutation accumulation and antagonistic pleiotropy. It provides an overview of approaches for quantifying G × A, emphasising the importance of function-valued trait models, such as the random regression animal model, and presents a critical review of the limited number of studies that have implemented these approaches in the context of wild populations. Finally, this chapter identifies a number of statistical issues/challenges that are likely to hold back much needed developments in this field and provides recommendations of ways to overcome these challenges as well as for avenues for future work.
The effects of others’ genes: maternal and other indirect genetic effects
Authors: McAdam Andrew G. , Garant Dany , Wilson Alastair J.
Published: August 2014

An individual’s phenotype may frequently be affected by the phenotypes (and hence genotypes) of other individuals with whom it interacts. Phenotypic effects that are caused by the genotype of another individual are referred to as indirect genetic effects, and these can have large and sometimes counterintuitive effects on evolutionary dynamics. Despite their potential importance, studies of indirect genetic effects in the wild are still rare. One class of indirect effect that has been investigated more commonly in natural populations is the effects of mothers on the phenotypes of their offspring. Maternal effects are defined as the contribution that a mother makes to the phenotypes of her offspring beyond the direct inheritance of genes from mother to offspring. Maternal effects have been widely studied phenotypically, and genetic variation in many important maternal traits has been quantified in the wild but rarely in the context of the indirect effects of this genetic variation on offspring traits. As a result, the importance of maternal genetic effects for evolutionary dynamics remains largely unexplored. This chapter provides conceptual background to the importance of maternal effects for evolution, and an overview of the various methods that can be employed to quantify maternal effects in the wild. Finally, this chapter provides some examples of important emerging questions in the field that could most rapidly advance our understanding of the importance of indirect genetic effects for evolutionary dynamics in the wild.
Case study: quantitative genetics and sexual selection of weaponry in a wild ungulate
Authors: Kruuk Loeske E. B. , Clutton-Brock Tim , Pemberton Josephine M.
Published: August 2014

This case study illustrates three key themes in current evolutionary quantitative genetics: the role of genetic associations in the evolutionary dynamics of selection, the insights gained from multivariate models, and the utility of a Bayesian Markov Chain Monte Carlo (MCMC) approach. This chapter presents a multivariate analysis of sexually selected weaponry, antlers in red deer, using data from a long-term study of a wild population of red deer. Using a Bayesian MCMC framework, the relationship between a component of fitness, male annual breeding success (ABS), and two antler traits (size (mass) and shape (the number of points, or form)) is estimated. Using a multivariate animal model to dissect these relationships revealed substantial positive environmental associations between each trait and ABS, presumably reflecting condition-dependence of both antler growth and the traits determining mating success. In contrast, a lack of genetic covariance between either trait and ABS suggested that neither would be predicted to evolve further via sexual selection. Furthermore, a significant difference between the genetic and the environmental multivariate gradients between antler form and fitness indicated a lack of causal effects on fitness. The analyses reveal a complex set of relationships not apparent at either a phenotypic or a univariate level, and suggest constraints to evolution despite the presence of genetic variance in the focal fitness component. This chapter also discusses advantages and problems associated with using multivariate quantitative genetic analyses to explore the process of selection in wild populations.
Evolutionary potential and constraints in wild populations
Authors: Teplitsky Céline , Robinson Matthew R. , Merilä Juha
Published: August 2014

This chapter asks: How can evolutionary potential be measured? The question is deceptively simple: whilst evolutionary potential is typically defined on a per-trait basis, it has become clear that the complex genetic architecture of quantitative traits requires other ways to quantify evolutionary potential and constraints. This chapter reviews knowledge about multivariate evolutionary potential in the wild and the extent to which genetic covariances, as summarized in the G-matrix, impact evolutionary trajectories of natural populations both in terms of rate and direction. In terms of constraints, genetic covariances among traits can slow down the rate of adaptation, and influence the direction of the response to selection. However, the constraints posed by genetic covariances are insurmountable only if G-matrices are stable. The chapter thus reviews firstly theoretical predictions about the stability of G in relation to selection, migration and drift, and secondly methods available to test differentiation among matrices. To date, a majority of studies imply conservatism of G-matrices; however, a couple of recent studies have revealed that differentiation of G-matrices among wild populations can also be very fast, especially during colonisation of new habitats. Furthermore, as an increasing number of methods have been proposed for comparing G-matrices, we assessed how these methods perform under different hypothetical scenarios. The chapter shows that limited statistical power could often lead to erroneous conclusion of matrix conservatism, suggesting caution is needed in interpreting the results of matrix comparisons. The chapter concludes by identifying areas in need of further research.
Phrase Structure and Argument Structure
Authors: Lohndal Terje
Published: August 2014

This book focuses on how syntax and meaning go together. It argues that two seemingly unrelated questions are actually intimately related: whether thematic arguments should be severed from the verb and whether there is a syntactic difference between specifiers and complements. Thus the book combines research in the domain of argument structure with research on phrase structure. It is argued that it is possible to create a mapping from syntax to logical form such that each syntactic Spell-Out domain corresponds to a conjunct at logical form. The book shows how one can adjust Spell-Out in order to achieve this, an operation which turns out to be closely related to whether or not the grammar distinguishes between specifiers and complements. An entire chapter is devoted to the latter issue, where it is shown that specifiers qua specifiers are not required by the grammar. The mapping is argued to be transparent in the sense that each conjunct at logical form is directly connected to a specific syntactic domain. The book closes with a discussion of compositionality in some detail, arguing that a semantics based on conjunction is compositional.
The Syntax‐Semantics Mapping
Authors: Lohndal Terje
Published: August 2014

The goal of this chapter is to tie Chapters 2 and 3 together and provide a syntax that maps transparently onto logical forms where all thematic arguments are severed from the verb. Specifically Lohndal argues that an argument is semantically tied to a head iff it is a sister of that head. The chapter starts out by presenting its syntactic assumptions before turning to the mapping hypothesis itself. A few alternative mapping hypotheses are also considered before the semantic composition operations are scrutinized. Lastly the chapter presents a number of syntactic consequences of the theory: Spell-Out, movement, linearization, thematic uniqueness, and agreement.
The interpretation of indefinites in future tense sentences: A novel argument for the modality of will?
Authors: Del Prete Fabio
Published: August 2014

The chapter considers two semantic issues concerning will-sentences: Stalnaker’s Asymmetry and modal subordination in Karttunen-type discourses. The former points to a distinction between will and modal verbs, seeming to show that will does not license non-specific indefinites. The latter, conversely, suggests that will-sentences involve some kind of modality. To account for the data, the chapter proposes that will is semantically a tense, hence it doesn’t contribute a quantifier over modal alternatives; a modal feature, however, is introduced in the interpretation of a will-sentence through a supervaluational strategy universally quantifying over possible futures. That this is not part of will’s lexical semantics is shown to have consequences that ultimately contribute to explain Stalnaker’s Asymmetry. Furthermore, that a modal quantification is present in the interpretation of a will-sentence is shown to imply the availability of modal subordination in Karttunen-type discourses.
Causal chains for futurates
Authors: Copley Bridget
Published: August 2014

One problem for accounts of future reference is the fact that there are different ways to refer to future times. In a strictly temporal theory of future reference, the differences must be temporal, and in a branching framework that treats future reference as quantifying over possible worlds, the differences must either be temporal or stem from the use of different sets of worlds. This chapter contrasts two different kinds of future reference: sentences with ‘real’ futures and futurate sentences, to argue that understanding the latter requires the notion of causal relations between events or event-like entities. Consequently, it is the causal relations inside the verb phrase that give rise to the future reference in futurates, rather than a temporal or branching future operator.
Markers of futurity and aspect in West Greenlandic
Authors: Trondhjem Naja
Published: August 2014

Originally Inuit languages had a temporal opposition between future and non-future. Over time, Iñupiaq has evolved an opposition between past, present, and future, while Inuktitut and West Greenlandic (WG) have retained the future/non-future opposition. This chapter will show that it is incorrect to describe WG as tenseless; WG has grammaticalized tense affixes. There are five such future-tense affixes: -ssa ‘future’, -niar ‘inevitable future’, -jumaar ‘vague future’, -ssamaar ‘planned future’, and -ler ‘near future’. The first three also have modal meanings: -ssa ‘should’, -niar ‘intention’, -jumaar ‘promise’. While, ssamaar has only one meaning, -ler has an additional three: two in the inner phasal aspect (‘begin’ and ‘be about to’), and one in outer phasal aspect (‘be about to’). This chapter shows that it is necessary to pay close attention to morphological structure, and to allow for the possibility that tense can be expressed by derivational affixes.
Balance Sheet Recessions and Time-Varying Coefficients in a Phillips Curve Relationship: An Application to Finnish Data
Authors: Juselius KatarinaM , Juselius Mikael
Published: August 2014

Edmund Phelps (1994) introduced a modified Phillips curve where the natural rate of unemployment is a function of the real interest rate instead of a constant. Koo (2010) argues that the effect of the interest rate on the macro economy is likely to be diluted during a balance sheet recession such as those recently seen in many countries. In the late 1980s, after having deregulated credit and capital movements, Finland experienced a housing boom which subsequently developed into a serious economic crisis similar to the recent ones. To learn from the Finnish experience we estimate the Phelps modified Phillips curve and use a Smooth Transition (STR) model to distinguish between ordinary periods and balance sheet recessions.
Fundamental Problems with Nonfundamental Shocks
Authors: Lütkepohl Helmut
Published: August 2014

Economic agents using information that is not incorporated in the econometric model is seen as a possible reason for why nonfundamental shocks are important in econometric models. Allowing for nonfundamental shocks in structural vector autoregressive (SVAR) analysis by considering moving average (MA) representations with roots in the complex unit circle is a possible response to the problem. Such models lead to nonlinear optimal forecast functions in general and are in this sense nonlinear models. A case is made for viewing nonfundamentalness as an omitted variables problem rather than a problem of MA roots in the unit circle. The omitted variables problem will always lurk in the background of SVAR analysis as well as other econometric studies and cannot be avoided. In SVAR analysis it is even more problematic than what the literature on nonfundamental shocks suggests.
Penalized Estimation of Semi-Parametric Additive Time-Series Models
Authors: Medeiros Marcelo C. , Mendes Eduardo F.
Published: August 2014

This paper studies oracle properties of ℓ1-penalized least squares estimator, such as the LASSO, in a semi-parametric regression setting with dependent data. We extend previous results in the literature of semi-parametric models and show that sparsity oracle inequalities for the LASSO also hold in a time-series environment. The results are valid even when the dimension of the model is (much) larger than the sample size and the regression matrix is not positive definite. Our results are derived when the nonparametric component is approximated by a linear combination of known basis functions (sieves), such that the approximating model is linear in the parameters. We advocate the use of a set of randomly generated logistic functions to approximate the nonparametric component of the model. Both simulations and an empirical exercise with Brazilian energy consumption data deliver promising results.
Asymmetric Dependence Patterns in Financial Returns: An Empirical Investigation Using Local Gaussian Correlation
Authors: Støve Bård , Tjøstheim Dag
Published: August 2014

A number of studies have provided evidence that financial returns exhibit asymmetric dependence, such as increased dependence during bear markets, but there seems to be no agreement as to how such asymmetries should be measured. We introduce the use of a new measure of local dependence to study this asymmetry. The central idea of the new approach is to approximate an arbitrary bivariate return distribution by a family of Gaussian bivariate distributions. At each point of the return distribution there is a Gaussian distribution that gives a good approximation at that point. The correlation of the approximating Gaussian distribution is taken as the local correlation in that neighborhood. The new measure does not suffer from the selection bias of the so-called conditional correlation in case of Gaussian data, and is able to capture nonlinear dependence. Analysing several financial returns from the US, UK, and German markets, we confirm and are able to explicitly quantify the asymmetry. Finally, we point out a number of possible extensions.
Bagging Constrained Equity Premium Predictors
Authors: Hillebrand Eric , Lee Tae-Hwy , Medeiros Marcelo C.
Published: August 2014

The literature on excess return prediction has considered a wide array of estimation schemes, among them unrestricted and restricted regression coefficients. We consider bootstrap aggregation (bagging) to smooth parameter restrictions. Two types of restrictions are considered: positivity of the regression coefficient and positivity of the forecast. Bagging constrained estimators can have smaller asymptotic mean-squared prediction errors than forecasts from a restricted model without bagging. Monte Carlo simulations show that forecast gains can be achieved in realistic sample sizes for the stock return problem. In an empirical application using the data set of Campbell and Thompson (2008), we show that we can improve the forecast performance further by smoothing the restriction through bagging.
Inviscid Incompressible Flows
Authors: Ruban Anatoly I. , Gajjar Jitesh S. B.
Published: August 2014

This chapter starts by formulating the Euler equations and the boundary condition for inviscid flow, namely the impermeability condition on a rigid-body surface. The Bernoulli integral for incompressible flows is derived, as is the Cauchy–Lagrange integral, and Kelvin’s Circulation Theorem is proved. This theorem is used to identify situations where a flow can be treated as potential. Two examples of three-dimensional potential flows are considered: flow past a motionless sphere and flow produced by a sphere moving through stagnant fluid. In this chapter, attention is principally paid to two-dimensional potential flows, for which the flow analysis reduces to finding a suitable analytic function as the complex potential in the complex plane. The method of conformal mapping is discussed in detail and is used to analyse a number of flows, including flows past Joukovskii aerofoils. The chapter concludes by describing Kirchhoff flow, for which purpose free-streamline theory is used.
Acceleration of short and long DNA read mapping without loss of accuracy using suffix array
Authors: Tárraga Joaquín , Arnau Vicente , Martínez Héctor , Moreno Raul , Cazorla Diego , Salavert-Torres José , Blanquer-Espert Ignacio , Dopazo Joaquín , Medina Ignacio
Published: August 2014

HPG Aligner applies suffix arrays for DNA read mapping. This implementation produces a highly sensitive and extremely fast mapping of DNA reads that scales up almost linearly with read length. The approach presented here is faster (over 20× for long reads) and more sensitive (over 98% in a wide range of read lengths) than the current state-of-the-art mappers. HPG Aligner is not only an optimal alternative for current sequencers but also the only solution available to cope with longer reads and growing throughputs produced by forthcoming sequencing technologies.

Availability and implementation:  https://github.com/opencb/hpg-aligner.

Contact:  jdopazo@cipf.es or imedina@ebi.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Poretools: a toolkit for analyzing nanopore sequence data
Authors: Loman Nicholas J. , Quinlan Aaron R.
Published: August 2014

Motivation: Nanopore sequencing may be the next disruptive technology in genomics, owing to its ability to detect single DNA molecules without prior amplification, lack of reliance on expensive optical components, and the ability to sequence long fragments. The MinION™ from Oxford Nanopore Technologies (ONT) is the first nanopore sequencer to be commercialized and is now available to early-access users. The MinION™ is a USB-connected, portable nanopore sequencer that permits real-time analysis of streaming event data. Currently, the research community lacks a standardized toolkit for the analysis of nanopore datasets.

Results: We introduce poretools, a flexible toolkit for exploring datasets generated by nanopore sequencing devices from MinION™ for the purposes of quality control and downstream analysis. Poretools operates directly on the native FAST5 (an application of the HDF5 standard) file format produced by ONT and provides a wealth of format conversion utilities and data exploration and visualization tools.

Availability and implementation: Poretools is an open-source software and is written in Python as both a suite of command line utilities and a Python application programming interface. Source code is freely available in Github at https://www.github.com/arq5x/poretools

Contact:  n.j.loman@bham.ac.uk and aaronquinlan@gmail.com

Supplementary information: An IPython notebook demonstrating the functionality of poretools is in Github. Complete documentation is available at http://poretools.readthedocs.org.
Gene Expression Profiling of Tumors From Heavily Pretreated Patients With Metastatic Cancer for the Selection of Therapy
Authors: Rebollo Joseba , Sureda Manuel , Martinez Elena Mª. , Fernández-Morejón Francisco J. , Farré José , Muñoz Vicente , Fernández-Latorre Francisco , Manzano Ramón G. , Brugarolas Antonio
Published: August 2014

Background:

Recently, it has been shown that it is possible to identify tumor profiles of sensitivity for potentially useful drugs, both conventional and experimental, based on whole oligonucleotide microarray gene expression studies in heavily pretreated patients with metastatic solid tumors.

Methods:

Fresh-frozen tumor biopsies for molecular profiling (MP) were obtained from patients with advanced and refractory cancer. Total tumor and control tissue RNA was hybridized to a whole human genome oligonucleotide microarray. Differentially expressed genes interacting with potential therapeutic targets were identified. Results were complemented with DNA sequencing of selected driver genes and with immunohistochemistry and fluorescent “in situ” hybridization. The results were used to guide experimental treatment.

Results:

MP assays led to a potentially active available drug in 91.2% of the patients. The median number of available active drugs per tumor was 5 (range, 1 to 9). Nine treated patients were not evaluable for response. Partial response was observed in 18 patients (33%), stable disease in 22 patients (40%) (clinical benefit rate of 73%), and progression in 15 (27%). Overall median progression-free survival and overall survival were 8 and 13 months, respectively.

Conclusion:

MP-guided therapy is feasible and seems to improve the clinical outcome of extensively pretreated patients but prospective and confirmatory trials are needed.
Aneurinibacillus soli sp. nov., isolated from mountain soil
Authors: Lee Keun Chul , Kim Kwang Kyu , Eom Mi Kyung , Kim Jong-Shik , Kim Dae-Shin , Ko Suk-Hyung , Lee Jung-Sook
Published: August 2014

A novel bacterial strain designated CB4Twas isolated from soil from the Hallasan, Jeju, Korea. Strain CB4Twas found to be strictly aerobic, Gram-stain-positive, rod-shaped, motile and formed creamy greyish colonies on nutrient agar. The major fatty acids were identified as iso-C15 : 0and iso-C16 : 0, and the predominant isoprenoid quinone as MK-7. The cell-wall peptidoglycan contained glycine and alanine as the diagnostic amino acids and phosphatidyl-N-methylethanolamine, phosphatidylethanolamine, diphosphatidylglycerol and an unidentified aminophospholipid as the polar lipids. The genomic DNA G+C content of strain CB4Twas 46.5 mol%. Phylogenetic analysis, based on 16S rRNA gene sequence similarities, showed that strain CB4Tforms a deep branch within the genusAneurinibacillus, sharing the highest level of sequence homology withAneurinibacillus aneurinilyticusDSM 5562T(96.5 %). On the basis of the phenotypic, chemotaxonomic and phylogenetic characteristics, strain CB4Tis considered to represent a novel species within the genusAneurinibacillus, for which the nameAneurinibacillussolisp. nov. is proposed. The type strain is CB4T( = KCTC 33505T = CECT 8566T). An emended description of the genusAneurinibacillusis also proposed.
Terrimonas arctica sp. nov., isolated from Arctic tundra soil
Authors: Jiang Fan , Qiu Xia , Chang Xulu , Qu Zhihao , Ren Lvzhi , Kan Wenjing , Guo Youhao , Fang Chengxiang , Peng Fang
Published: August 2014

A novel, Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated R9-86T, was isolated from tundra soil collected near Ny-Ålesund, Svalbard Archipelago, Norway (78° N). Growth occurred at 4–28 °C (optimum, 22–25 °C) and at pH 6.0–9.0 (optimum, pH 7.0). Flexirubin-type pigments were absent. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain R9-86T belonged to the genus

Terrimonas

in the family

Chitinophagaceae

. 16S rRNA gene sequence similarities between strain R9-86T and the type strains of species of the genus

Terrimonas

with validly published names ranged from 93.7 to 95.0 %. Strain R9-86T contained iso-C15 : 1-G (25.7 %), iso-C15 : 0 (24.5 %), iso-C17 : 0-3OH (18.3 %) and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c, 8.7 %) as its major cellular fatty acids; phosphatidylethanolamine and an unknown polar lipid as its main polar lipids, and MK-7 as its predominant respiratory quinone. The DNA G+C content was 48.4 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain R9-86T is considered to represent a novel species of the genus

Terrimonas

, for which the name Terrimonas arctica sp. nov. is proposed. The type strain is R9-86T ( = CCTCC AB 2011004T = NRRL B-59114T).
An outbreak of bla OXA-51-like- and bla OXA-66-positive Acinetobacter baumannii ST208 in the emergency intensive care unit
Authors: Asai Satomi , Umezawa Kazuo , Iwashita Hideo , Ohshima Toshio , Ohashi Maya , Sasaki Mika , Hayashi Hideki , Matsui Mari , Shibayama Keigo , Inokuchi Sadaki , Miyachi Hayato
Published: August 2014

A series of clinical isolates of drug-resistant (DR)Acinetobacter baumanniiwith diverse drug susceptibility was detected from eight patients in the emergency intensive care unit of Tokai University Hospital. The initial isolate was obtained in March 2010 (A. baumanniiTokai strain 1); subsequently, seven isolates were obtained from patients (A. baumanniiTokai strains 2–8) and one isolate was obtained from an air-fluidized bed used by five of the patients during the 3 months from August to November 2011. The isolates were classified into three types of antimicrobial drug resistance patterns (RRR, SRR and SSR) according to their susceptibility (S) or resistance (R) to imipenem, amikacin and ciprofloxacin, respectively. Genotyping of these isolates by multilocus sequence typing revealed one sequence type, ST208, whilst that by a DiversiLab analysis revealed two subtypes. All the isolates were positive forblaOXA-51-likeandblaOXA-66, as assessed by PCR and DNA sequencing.A. baumanniiTokai strains 1–8 and 10 (RRR, SRR and SSR) had quinolone resistance-associated mutations ingyrA/parC, as revealed by DNA sequencing. The ISAba1upstream ofblaOXA-51-likeand aminoglycoside resistance-associated gene,armA, were detected inA. baumanniiTokai strains 1–7 and 10 (RRR and SRR) as assessed by PCR. Among the genes encoding resistance–nodulation–division family pumps (adeB, adeGandadeJ) and outer-membrane porins (oprDandcarO), overexpression ofadeBandadeJand suppression ofoprDandcarOwere seen in isolates ofA. baumanniiTokai strain 2 (RRR), as assessed by real-time PCR. Thus, the molecular characterization of a series of isolates of DRA. baumanniirevealed the outbreak of ST208 and diverse antimicrobial drug susceptibilities, which almost correlated with differential gene alterations responsible for each type of drug resistance.
A viral transcription factor exhibits antiviral RNA silencing suppression activity independent of its nuclear localization
Authors: Lukhovitskaya Nina I. , Vetukuri Ramesh R. , Sama Indu , Thaduri Srinivas , Solovyev Andrey G. , Savenkov Eugene I.
Published: August 2014

Viral suppressors of RNA silencing (VSRs) are critical for the success of virus infection and efficient accumulation of virus progeny. The chrysanthemum virus B p12 protein acts as a transcription factor to regulate cell size and proliferation favourable for virus infection. Here, we showed that the p12 protein suppressed RNA silencing and was able to complement a VSR-deficient unrelated virus. Moreover, p12 counter-silencing activity could be uncoupled from its function as a transcription factor in the nucleus. The altered p12 protein, which lacked a nuclear localization signal and was not imported into the nucleus, was able to suppress RNA silencing as efficiently as the native protein. The data revealed new aspects of p12 functioning and identified a novel role for this viral zinc-finger transcription factor. The results provided a general insight into one of the activities of the p12 protein, which appeared to possess more than one function.
Emergent Speciation by Multiple Dobzhansky–Muller Incompatibilities
Authors: Paixão Tiago , Bassler Kevin E. , Azevedo Ricardo B. R.
Published: August 2014

The Dobzhansky–Muller model posits that incompatibilities between alleles at different loci cause speciation. However, it is known that if the alleles involved in a Dobzhansky–Muller incompatibility (DMI) between two loci are neutral, the resulting reproductive isolation cannot be maintained in the presence of either mutation or gene flow. Here we show that speciation can emerge through the collective effects of multiple neutral DMIs that cannot, individually, cause speciation—a mechanism we call emergent speciation. We investigate emergent speciation using models of haploid holey adaptive landscapes—neutral networks—with recombination. We find that certain combinations of multiple neutral DMIs can lead to speciation. Furthermore, emergent speciation is a robust mechanism that can occur in the presence of migration, and of deviations from the assumptions of the neutral network model. Strong recombination and complex interactions between the DMI loci facilitate emergent speciation. These conditions are likely to occur in nature. We conclude that the interaction between DMIs may cause speciation.

Author Summary

Most species are kept distinct by incompatibilities between the genes they carry. These genetic incompatibilities cause hybrids between the species to have low fitness. Here we propose that combinations of several incompatibilities can collectively cause the origin of species, although they cannot do so acting alone—a mechanism we call emergent speciation. We use flat fitness landscapes with many holes in them to extend the classic Dobzhansky–Muller model, and capture the essence of the phenomenon. We find that emergent speciation can, indeed, occur through the combined effects of multiple genetic incompatibilities. Furthermore, the conditions that facilitate emergent speciation are likely to occur in nature. We conclude that the interaction between genetic incompatibilities may be a root cause of the origin of species.
Heterogeneous housing markets: structural implications for pricing and risk
Authors: A. Borgersen Trond
Published: August 2014

Purpose

– The purpose of this paper is to compare the structure of risk and the structure of pricing in housing markets where the interaction between segments is taken into account with the structures that come about in a housing market approach that ignores this interplay. Knowing how most empirical assessments of whether housing markets are in or out of equilibrium is related to macroeconomic variables and is ignoring the interplay between segments our aim is to highlight the extent to which a homogeneous market framework underestimates pricing and risk in real housing markets.

Design/methodology/approach

– Framed in terms of a linearized housing market with two segments, the author derives expressions for house prices and house price risk in three scenarios. The author compares the structure of pricing and the structure of risk in a homogeneous housing market with those of two distinct heterogeneous housing markets where segments are linked as well analyzing as how prices and risk responds to shocks.

Findings

– The author derives expressions for market segment prices and for the house price index in three distinct housing market scenarios and shows how heterogeneous housing market frameworks produce both expressions for house prices and for house price risk, as well as a response in both risk and prices to shocks to demand, that deviate from those of a homogeneous housing market framework. While significantly underestimating house price risk a homogeneous framework might also be taken by surprise of the price response accompanying shocks to demand.

Originality/value

– The authors' simplistic expressions for house prices and house price risk provides a framework for bringing two distinct theoretical housing market camps onto the same playing field. The approach shows the value added of taking the interplay between market segments into account when analyzing housing market developments.
Homebuyers and the representation of spatial markets by information providers
Authors: J. Dunning Richard , Grayson Andrew
Published: August 2014

Purpose

– The purpose of this paper is to renew a research agenda considering the impact that information providers’ processes are having on the housing market; in particular to develop a research agenda around the role of the Internet in shaping households’ perceptions of the spatial nature of housing markets.

Design/methodology/approach

– This paper reviews the existing literature. It uses preliminary extensive survey findings about the role of the Internet in housing search to hypothesise ways in which households may be affected by this transition.

Findings

– Not applicable – other than evidence for the growth in the importance of the Internet in shaping households’ housing search.

Practical implications

– First, the academy needs to readdress the theory surrounding information acquisition and use insights from economics, sociology and psychology to understand these processes. Second, local authorities and academics should analyse the impact of Internet use on housing market boundaries (and the profound subsequent impact on policy traction). Third, estate agents should reconsider the role of the Internet in shaping housing markets and provide a critical response to the large property search engines.

Originality/value

– This paper reviews the literature and explores the necessity of a renewed interest in research on the role of information sources in framing and constraining housing search behaviour.
The grabber: making a first impression the Wilsonian way
Authors: Jacobsson Mattias , Hällgren Markus
Published: August 2014

Purpose

– The purpose of this paper is to contribute to the understanding of what a good grabber is and how to construct one. This is done by drawing on the insights provided by Professor Timothy L. Wilson, for whom this paper is written as an “honorary piece.”

Design/methodology/approach

– The paper is based on a small sample of papers from the 48 journals that have received contributions from Professor Wilson throughout the years. A total of 12 papers have been selected, using a mix of convenience and haphazard sampling. The grabber of each paper has then been analyzed based on its nature and style.

Findings

– Based on the review and analysis, five different types of grabbers were identified; the quote, the anecdote, the provocative question, the surprise, and the metaphor, each type representing a unique way (and strategy) of creating initial interest.

Research limitations/implications

– As this paper was intentionally based on a convenience sample, further investigation is needed to establish whether the presented categories have clear validity and/or whether there are additional categories/strategies for how to create good grabbers.

Originality/value

– Creation of interest is an increasingly important part of everyday academic practice. As the grabber is a rarely addressed phenomenon in academic literature, the presented categories should be of both interest and practical use to academics in most fields.
Asset management policies and guidelines of different states in Australia
Authors: Nateque Mahmood Muhammad , Prasad Dhakal Subas , Brown Kerry , Keast Robyn , Wiewiora Anna
Published: August 2014

Purpose

– The purpose of this paper is to explore and compare the asset management policies and practices of six Australian states – New South Wales, Victoria, Queensland, South Australia, Western Australia and Tasmania – to improve understanding of the policy context to best shape policy focus and guidelines. Australian state-wide asset management policies and guidelines are an emergent policy domain, generating a substantial body of knowledge. However, these documents are spread across the layers of government and are therefore largely fragmented and lack coherency.

Design/methodology/approach

– The comparative study is based on the thematic mapping technique using the Leximancer software.

Findings

– Asset management policies and guidelines of New South Wales and Victoria have more interconnected themes as compared to other states in Australia. Moreover, based on the findings, New South Wales has covered most of the key concepts in relation to asset management; the remaining five states are yet to develop a comprehensive and integrated approach to asset management policies and guidelines.

Research limitations/implications

– This review and its findings have provided a number of directions on which government policies can now be better constructed and assessed. In doing so, the paper contributes to a coherent way forward to satisfy national emergent and ongoing asset management challenges. This paper outlines a rigorous analytical methodology to inform specific policy changes.

Originality/value

– This paper provides a basis for further research focused on analyzing the context and processes of asset management guidelines and policies.