bluuebunny/crossref_metadata_2025 huggingface dataset:
How Not to End a Saga, Unless...: Chapters 146–59
Authors: Miller William Ian
Published: August 2014

This chapter discusses the author’s difficulty in bringing closure to the saga. Can it really be the case that the Hildigunn we know would let herself be married to one of the killer’s of her husband? The problem of the Clontarf episode and several proposed explanations for why the saga ends as it does are considered. Does the episode represent the author’s palinode, a pious retraction of his earlier skepticism regarding miracles, of his making the pre-Christian period rather less politically and legally dysfunctional than the post-Conversion polity? Finally, are these chapters really his proof that his saga is the only true saga of the Burning, as he has Kari hunt down any tellers of variant versions? Kari’s pilgrimage to Rome is contrasted to Flosi’s, the latter penitent, the former a signal that, as far as he is concerned, the feud is now over.
Introduction
Authors: Miller William Ian
Published: August 2014

The introduction includes some general comments on Iceland and saga writing and on 'Njáls saga's' place in the history of saga writing. It discusses basic historical and social background, the division of the country into quarters, the local administrative unit known as the hreppr, as well as an overview of Thing organization, chieftains and chieftaincies, and some matters of legal procedure. There is discussion of the word ‘thing’. A plot summary is provided as an aid to the reader who does not have the saga before him, for the plot is complex and the cast of characters who matter is large. It contains basic remarks on saga style, depiction of characters’ psychology and their motives for action.
Conclusion
Authors: Okita Kiyokazu
Published: August 2014

The final section summarizes the previous four chapters and ties them back to the issues discussed in introduction. This book contributes to genealogical study in South Asian culture by examining the idea of tradition or sampradāya in the early modern period. This focus on the early modern period in turn shows that in the realm of Vedānta too there was a lively production of Sanskrit texts, as pointed out by the Sanskrit Knowledge Systems Project. One of the unique featires of Vedānta in this period was its focus on the Purāṇas, as demonstrated in the works of Madhva, Śrīdhara, Jīva, and of Baladeva. Therefore this study shows a deep influence of Purāṇic texts on Vedānta, which has not received much attention to date. Finally, this work contributes to the establishment of Hindu theology as a legitimate intellectual category. The writings of the Gauḍīya authors evidently fit well with three definitions of theology.
The Printed Page
Authors: Luna Paul , Ould Martyn
Published: August 2014

The chapter considers the visual character of the Press's books: their typography and layout; the use of illustration, especially in engraving; and the development of an ‘Oxford page’. The various types used for printing Latin, English, Greek, and other languages are catalogued and their origins traced. The chapter discusses different methods of illustration and makes a case study of the Oxford Almanack — describing its publication, distribution, and particularly its engravings. The chapter also addresses the complex requirements of combining text and illustration in mathematical and anatomical texts and in typesetting pages with multiple languages, such as dictionaries and commentaries on scriptural or classical texts. In general, margins grew more generous, chapter titles and sub-headings merited more space and title page typography was streamlined; changes to the Oxford printed page from the late sixteenth through the late eighteenth century exemplify larger developments in English and European typography.
Understanding Vision
Authors: Zhaoping Li
Published: August 2014

This book explains computational principles and models of biological visual processing, in particular, of primate vision. Vision scientists unfamiliar with mathematical details should be able to conceptually follow the theoretical principles and their relationship with physiological, anatomical, and psychological observations, without going through the more mathematical pages. For readers with a physical science background, especially those from machine vision, this book serves as an analytical introduction to biological vision. It can be used as a textbook or a reference book in a vision course, or a computational neuroscience course, for graduate students or advanced undergraduate students. It is also suitable for self-learning by motivated readers. For readers with a focused interest in just one of the topics in the book, it is feasible to read just the chapter on this topic without having read or fully comprehended the other chapters. In particular, Chapter 2 is a brief overview of experimental observations on biological vision, Chapter 3 is on encoding of visual inputs, Chapter 5 is on visual attentional selection driven by sensory inputs, and Chapter 6 is on visual perception or decoding. There are many examples throughout the book to illustrate the application of computational principles to experimental observations.
Approach and scope
Authors: Zhaoping Li
Published: August 2014

This book’s approach to understand vision is by linking neural substrates in the brain with visual perceptual behavior through the use of theory and models. This chapter proposes to view vision as containing three roughly successive stages: visual input encoding, visual information selection by attention, and visual recognition or perception by visual decoding. In contrast to traditional views, which decompose vision to low-level, mid-level, and high-level processes, the proposed three-stage view makes explicit the separate tasks in vision and highlights the role of vision selection, which admits a tiny fraction of visual input information through the attentional bottleneck for visual decoding. This chapter previews the topics in each of the three stages that will be covered in the rest of the book, noting that we have the least understanding about the visual decoding stage.
Visual recognition as decoding
Authors: Zhaoping Li
Published: August 2014

This chapter gives an account of the experimental and computational investigations in visual perception or recognition. The perceptions, including illusions, are viewed as the outcomes of inferring or decoding properties of visual scenes from the neural responses to the visual inputs. Emphasis is on understanding perception at both physiological and behavioral levels through the use of computational principles. Maximum-likelihood decoding and Bayesian decoding approaches are introduced. Examples are provided to use these approaches to understand, e.g., contrast detection, color discrimination, motion direction perception, depth illusion, and influences of context and prior experience in visual perception. Limits in the visual decoding performance, due to inefficiency in utilizing the visual input information, likely caused by the attentional bottleneck, are highlighted. Likely neural architectures to implement decoding are discussed.
Molecular Evolution
Authors: Yang Ziheng
Published: August 2014

This book summarizes the statistical models and computational algorithms for comparative analysis of genetic sequence data in the fields of molecular evolution, molecular phylogenetics, and statistical phylogeography. The book presents and explains the models of nucleotide, amino acid, and codon substitution, and their use in calculating pairwise sequence distances and in reconstruction of phylogenetic trees. All major methods for phylogeny reconstruction are covered in detail, including neighbour joining, maximum parsimony, maximum likelihood, and Bayesian methods. Using motivating examples, the book includes a comprehensive introduction to Bayesian computation using Markov chain Monte Carlo (MCMC). Advanced topics include estimation of species divergence times using the molecular clock, detection of molecular adaptation, simulation of molecular evolution, as well as species tree estimation and species delimitation using genomic sequence data.
The Evolution of Sex Determination
Authors: Beukeboom Leo W. , Perrin Nicolas
Published: August 2014

Sexual reproduction is a fundamental aspect of life. It is defined by the occurrence of meiosis and the fusion of two gametes of different sexes or mating types. Genetic mechanisms for the determination and differentiation of the two sexes are diverse and evolutionary labile. This book synthesizes the contemporary literature on patterns and processes of sex determination evolution. The first chapter introduces definitions and concepts of sexual reproduction. Chapter 2 provides a comprehensive classification of sex-determination systems and describes the diversity of sexual cycles across eukaryote lineages, from excavates to mammals. Subsequent chapters detail the molecular mechanisms and quantitative genetics of sex determination (Chapters 3 and 4), examine the processes of sex-chromosome evolution (Chapter 5), and discuss life-history consequences of sex-determination systems (Chapter 6). The final chapter addresses the evolutionary processes responsible for the diversity and turnover in sex determination (Chapter 7). The book provides an overview of different sex-determination systems and details of its molecular regulation in fungi, plants, and animals, many of which are covered in separate text boxes and figures. It is argued that sex determination and primary sex differentiation cannot be regarded as separate processes and that the traditional dichotomous view of genotypic (GSD) and environmental (ESD) sex determination is no longer accurate. Ample documentation is provided about how sex determination affects, and is affected by, various forms of sexual conflict, sexual selection, and speciation. The book makes clear that sex-determination evolution will remain a highly dynamic field of research in the future.
The evolution of sex chromosomes
Authors: Beukeboom Leo W. , Perrin Nicolas
Published: August 2014

The chromosomes carrying the genes that determine sexes or mating types often show strong heteromorphy. This chapter discusses the evolutionary trajectories of sex chromosomes, from the initial acquisition of a sex-determining gene, to the linkage of sexually antagonistic genes, and the suppression of recombination. The ensuing degeneration of non-recombining regions may occur in several steps, as testified by evolutionary strata. This process may end in the loss of the degenerated chromosome and its replacement by a proto sex chromosome evolving from an autosomal pair. The several genomic processes stemming from sex linkage and recombination arrest differ between the haploid (U or V), homogametic (X or Z) and heterogametic (Y or W) chromosomes, resulting in specific and divergent evolutionary fates. Several mechanisms (such as gene conversion and retention of X-Y recombination) may oppose the degeneration, whereas various forms of dosage compensation may accommodate it. Although strongly heteromorphic in some lineages, sex chromosomes have remained homomorphic in others, which requires further study.
Four decades of estimating heritabilities in wild vertebrate populations: improved methods, more data, better estimates?
Authors: Postma Erik
Published: August 2014

After over four decades of attempting to disentangle the role of genetic and the various sources of environmental variation in natural populations, what has been learned about the absolute and relative role of genes and the environment in shaping phenotypic variation? This chapter explores how new methodological developments, and the application of the animal model in particular, have changed and shaped quantitative genetic studies of natural populations. In particular, this chapter assesses i) whether the estimates of absolute and relative amounts of genetic and environmental variation, as well as their accuracy, are affected by the method employed (e.g. parent–offspring regression vs animal model), ii) whether they have changed over time, and iii) if they have, what are the causes of these changes. A literature search was performed to find studies that estimated heritabilities, with the search limited to estimates based on individual-based data on free-living vertebrate populations. This resulted in a database containing over 1600 heritability estimates, for a wide range of species and traits, and estimated using a variety of methods. Using these data, this chapter goes on to show how heritabilities are being estimated for an increasing number of traits, and that these heritabilities have become more accurate and probably less biased over time, but that heritability estimates for individual traits have changed remarkably little. The implications of these findings for the understanding of the generation and maintenance of the ubiquitous amounts of variation present are discussed, and suggestions for future research are made.
Dominance genetic variance and inbreeding in natural populations
Authors: Wolak Matthew E. , Keller Lukas F.
Published: August 2014

It is assumed that dominance genetic variance contributes little to the prediction of evolutionary change in polygenic traits. This is based on the assumption that populations are large, panmictic, and randomly mating. However, the ecological contexts of most wild populations studied to date violate one, if not several, of these assumptions, and the widespread occurrence of inbreeding and inbreeding depression of phenotypic traits and fitness suggests dominance genetic effects are ubiquitous. This chapter reviews what genetic dominance represents at the level of a single locus and how this contributes to phenotypic variation and discusses how to estimate dominance variance with emphasis on the complications arising in wild populations and with inbreeding. Next, empirical estimates of dominance variance are reviewed. Since no estimates exist of dominance variance in the wild (except for humans), laboratory and agricultural populations are examined, and it is shown that dominance variance is a major contributor to phenotypic variation and in some cases contributes as much as additive genetic variance. This chapter also discusses how inbreeding and dominance affect predictions of evolutionary change, and ends with a review of some of the empirical questions for which genetic dominance is an important quantity in its own right. In this chapter, it is argued that dominance variance has been ignored for too long, may hamper the ability to predict evolutionary change, can be a major contributor to phenotypic variance, is interesting to study in its own right, and provides many avenues of research to be addressed by empirical study.
Cross-pollination of plants and animals: wild quantitative genetics and plant evolutionary genetics
Authors: Stinchcombe John R.
Published: August 2014

Evolutionary quantitative genetics, as applied to natural populations, sits at an interesting cross-road. Studies of long-lived, mobile animals have given us a first glimpse of the expression of genetic variation, natural selection, and evolution in free-living organisms. A parallel and largely non-overlapping evolutionary literature focuses on plants, which ‘sit still and wait to be counted’ to use John Harper’s phrase. These studies, which are almost exclusively single-generation experiments or common garden studies using a quantitative genetic mating design, have revealed abundant evidence for local adaptation, genotype × environment interactions for traits and fitness, and ecological context dependence of selection. Consequently, researchers are in the curious position where the life-histories of focal organisms have potentially constrained understanding: the insights into and potential role of local adaptation and genotype × environment interactions are difficult to apply to long-lived organisms not amenable to experimental manipulation. Similarly, the benefits of long-term monitoring, studying evolution in the wild, and characterising the natural expression of genetic variation in the field have been difficult to apply to short-lived plants, mainly due to the problems posed by seed banks and the difficulty of determining parentage in populations where individuals may have hundreds to thousands of offspring. This chapter explores the conceptual, analytical, and biological insights that might be obtained by applying lessons and techniques of experimental studies in plant evolutionary ecology to studies of wild vertebrate populations, and vice-versa.
Quantitative genetics of wild populations of arthropods
Authors: Zajitschek Felix , Bonduriansky Russell
Published: August 2014

This chapter discusses how genetic variation in fitness-related traits can be assessed in wild populations of arthropods and how the state of this research has developed in the recent past, including the use of genomic data. Understanding genetic variation in fitness within natural populations of invertebrates is of considerable theoretical importance, yet pure field estimates of quantitative genetic parameters of invertebrate species are almost non-existent. The reasons why many insect species are established model species for lab studies are identical to the problems researchers face in their attempts to study them in their natural habitat: they are small, short-lived and often can have a large number of offspring. There is a large literature on field-lab estimates (using data from laboratory reared offspring of field-derived parents), but this approach is not ideal in a number of ways. This chapter suggests potential ways to ameliorate these problems, and discusses some examples of suitable model systems. Systems such as these, and new approaches to tracking individuals and estimating relatedness, will ultimately enable researchers to estimate quantitative genetic parameters for natural populations of invertebrates. Such studies will allow for comparison with the enormous literature on captive invertebrate populations, as well as extend knowledge of the quantitative genetics of natural populations to a much broader range of biological diversity.
Epigenetic processes and genetic architecture in character origination and evolution
Authors: Badyaev Alexander V. , Walsh J. Bruce
Published: August 2014

The complexity of biological systems often prevents the construction of deterministic framework for the relationship between genotypes and phenotypes in development and evolution. The void is filled by the field of epigenetics that studies properties of emergent, self-regulatory, and compensatory interactions that arise above the level of the gene, but are not directly predictable from the intrinsic properties of either phenotype or genotype. Although these interactions are ubiquitous in the development and functioning of phenotypes, their imprint on the evolution of genetic architecture is unclear. This chapter particularly addresses the contribution of epigenetic developmental dynamics to the maintenance of multivariate genetic variation in complex traits that are subject to strong natural selection. The chapter brings together geometric and developmental perspectives to understanding the evolution of genetic architecture that reconciles precise adaptation, evolutionary diversification, and environmentally contingent developmental variation.
Introduction
Authors: Lohndal Terje
Published: August 2014

This chapter outlines the core assumptions of the book. It starts out by introducing the particular version of the Minimalist Program assumed in this book. This is followed by a discussion of different approaches to argument structure. These are called the lexicalist approach and the constructivist approach. This background is especially useful in order to situate the discussion in Chapter 2 in a broader context. Towards the end of the chapter, some general issues relating to the syntax–semantics interface are discussed, before a roadmap is provided.
The Size of a Verb
Authors: Lohndal Terje
Published: August 2014

Most linguists learn at some point that verbs have arguments. This chapter questions this view and concludes that it is wrong. It is argued that verbs do not have adicities beyond a single event variable, in accordance with the Neo-Davidsonian approach to formal semantics that this book adopts. The chapter focuses on Kratzer’s (1996) argument that the Agent but not the Theme is severed from the verb’s lexical representation, and it outlines Schein’s (1993) argument that the Agent must be severed from the verb. Then a section on the Theme follows, including data involving, among others, reciprocals, adjectival passives, and focus. Then a lengthy discussion of verbal adicity follows, concluding that such variability argues in favor of verbs not having any thematic arguments.
Specifiers and Phrase Structure
Authors: Lohndal Terje
Published: August 2014

Specifiers have occupied a central role in the history of generative grammar. The goal of the present chapter is to argue that specifiers qua specifiers do not play a role as the target of various grammatical operations. This book argues that we should maintain the distinction between heads and phrases, but that a head bears the same relation to a complement as it does to a specifier. In various cases where specifiers have been argued to be important, the chapter shows that other mechanisms might be at work (e.g., Agree instead of spec–head licensing) or that the issue at hand is not really related to specifiers qua specifiers (e.g., the subject requirement, extraction from phrases in specific position).
Semantic Competence and Compositionality
Authors: Lohndal Terje
Published: August 2014

This chapter discusses some broader issues that arise from the specific perspective developed in this book. In particular the relationship between grammatical and conceptual meaning is considered in detail. Following Bouchard (1995) in part, the chapter argues that a lot of what are typically taken to be facts about argument structure really are facts about conceptual structure. Furthermore, based on Dowty (2007), it is argued that compositionality is not something that can be defined a priori, and that its content comes from our conception of what sorts of object meanings can and cannot be, and consequently what kind of operations can and cannot be used in order to yield meanings that human beings employ.
Future tense, prospective aspect, and irrealis mood as part of the situation perspective: Insights from Basque, Turkish, and Papuan
Authors: Jendraschek Gerd
Published: August 2014

Beginning with three descriptive case studies from Turkish, Basque, and the Papuan language Iatmul, the chapter identifys structural means to express future time reference in these languages, and the morphosyntactic characteristics, polysemy, and, diachrony of the relevant morphemes and constructions are described. Markers often glossed as ‘future’ are more appropriately labelled ‘prospective’ or ‘irrealis’, while the distinction between prospective aspect and future tense also depends on the extent to which a prospective construction is grammaticalized. While a present prospective can develop into a future, past prospectives tend to take over the function of counterfactual conditionals in the past. Aspect, tense, and mood should therefore be defined as prototype categories within the macro-category ‘situation perspective’. Diachronic shift and synchronic overlap between the micro-categories are a consequence of their being connected by grammaticalization scales. All TAM marking contributes to the situation perspective; while aspect is the closest perspective, epistemic modality is the most distant.
Evidential futures: The case of Spanish
Authors: Escandell-Vidal Victoria
Published: August 2014

In Spanish there is no systematic correlation between future tense and future time reference. This is shown by, at least, three facts: the range of possible interpretations for the inflected future ; the late acquisition of the future tense as a means of expressing futurity; and the prevalence of the periphrastic future construction ‘ir a + inf.’ as the most usual way to express futurity in all dialects. A natural explanation requires the following hypothesis to be accepted: the inflected future in Spanish encodes neither temporal nor modal information, but an evidential meaning. The inflected future encodes a procedural instruction to interpret the propositional content as the result of a mental process by the speaker. This hypothesis explains not only the variety of discourse uses, but also the otherwise surprising data of first language acquisition and the distribution of forms in spoken Spanish.
Testing for Neglected Nonlinearity Using Twofold Unidentified Models under the Null and Hexic Expansions
Authors: Cho Jin Seo , Ishida Isao , White Halbert
Published: August 2014

We revisit the twofold identification problem discussed by Cho, Ishida, and White (2011), which arises when testing for neglected nonlinearity by artificial neural networks. We do not use the so-called “no-zero” condition and employ a sixth-order expansion to obtain the asymptotic null distribution of the quasi-likelihood ratio (QLR) test. In particular, we avoid restricting the number of explanatory variables in the activation function by using the distance and direction method discussed in Cho and White (2012). We find that the QLR test statistic can still be used to handle the twofold identification problem appropriately under the set of mild regularity conditions provided here, so that the asymptotic null distribution can be obtained in a manner similar to that in Cho, Ishida, and White ( 2011). This also implies that the weighted bootstrap in Hansen (1996) can be successfully exploited when testing the linearity hypothesis using the QLR test.
Common Nonlinearities in Multiple Series of Stock Market Volatility
Authors: Anderson Heather M. , Vahid Farshid
Published: August 2014

Decreases in stock market returns often lead to higher increases in volatility than increases in returns of the same magnitude, and it is common to incorporate these so-called leverage effects in GARCH and stochastic volatility models. Recent research has also found it useful to account for leverage in models of realized volatility, as well as in models of the continuous and jump components of realized volatility. This chapter explores the use of smooth transition autoregressive (STAR) models for capturing leverage effects in multiple series of the continuous components of realized volatility. We find that the leverage effect is well captured by a common nonlinear factor driven by returns, even though the persistence in each country’s volatility is country specific. A three-country model that incorporates both country specific persistence and a common leverage effect offers slight forecast improvements for mid-range horizons, relative to other models that do not allow for the common nonlinearity.
Modeling Time-Varying Volatility in Financial Returns: Evidence from the Bond Markets
Authors: Amado Cristina , Laakkonen Helinä
Published: August 2014

The “unusually uncertain” phase in the global financial markets has inspired many researchers to study the effects of ambiguity (or “Knightian uncertainty”) on the decisions made by investors and their implications for the capital markets. We contribute to this literature by using a modified version of the time-varying GARCH model of Amado and Teräsvirta (2013) to analyze whether the increasing uncertainty has caused excess volatility in the US and European government bond markets. In our model, volatility is multiplicatively decomposed into two time-varying conditional components: the first being captured by a stable GARCH(1,1) process and the second driven by the level of uncertainty in the financial market.
Oracle Efficient Estimation and Forecasting With the Adaptive Lasso and the Adaptive Group Lasso in Vector Autoregressions
Authors: Callot Laurent A.F. , Kock Anders Bredahl
Published: August 2014

We show that the adaptive Lasso (aLasso) and the adaptive group Lasso (agLasso) are oracle efficient in stationary vector autoregressions where the number of parameters per equation is smaller than the number of observations. In particular, this means that the parameters are estimated consistently at a √T-rate, that the truly zero parameters are classified as such asymptotically, and that the non-zero parameters are estimated as efficiently as if only the relevant variables had been included in the model from the outset. The group adaptive Lasso differs from the adaptive Lasso by dividing the covariates into groups whose members are all relevant or all irrelevant. Both estimators have the property that they perform variable selection and estimation in one step. We evaluate the forecasting accuracy of these estimators for a large set of macroeconomic variables. The plain Lasso is found to be the most precise procedure overall. The adaptive and the adaptive group Lasso are less stable but mostly perform at par with common factor models.
Bias and Uncertainty in Analyst Earnings Expectations at Different Forecast Horizons
Authors: Aiolfi Marco , Rodriguez Marius , Timmermann Allan
Published: August 2014

Financial analysts’ earnings forecasts are upwards biased with a bias that gets bigger, the longer the forecast horizon. One explanation of this bias is that it reflects asymmetric loss of positive and negative forecast errors: a positive bias may benefit analysts but also compromises the accuracy of their forecasts, especially at short horizons. We use the linex loss function proposed by Varian (1975) and show that this model can generate a monotonically decreasing bias in forecast errors as a function of the length of the forecast horizon.
Fundamentals of Fluid Dynamics
Authors: Ruban Anatoly I. , Gajjar Jitesh S. B.
Published: August 2014

This chapter starts with a discussion of the continuum hypothesis and the conditions under which it can be used. The origin of the internal forces acting in moving fluids is then identified and the notion of the surface stress and the stress tensor are introduced, as is the rate-of-strain tensor. The constitutive equation, which relates the surface stress to the deformational motion of a fluid, is then derived. Newton’s Second Law and the law of conservation of energy are applied to deduce the equations governing fluid motion. These are known as the Navier–Stokes equations. They are derived for both incompressible fluid flows and compressible flows of a perfect gas. The chapter concludes with a demonstration of how the Navier–Stokes equations can be expressed in curvilinear coordinates.
FACTERA: a practical method for the discovery of genomic rearrangements at breakpoint resolution
Authors: Newman Aaron M. , Bratman Scott V. , Stehr Henning , Lee Luke J. , Liu Chih Long , Diehn Maximilian , Alizadeh Ash A.
Published: August 2014

Summary: For practical and robust de novo identification of genomic fusions and breakpoints from targeted paired-end DNA sequencing data, we developed Fusion And Chromosomal Translocation Enumeration and Recovery Algorithm (FACTERA). Our method has minimal external dependencies, works directly on a preexisting Binary Alignment/Map file and produces easily interpretable output. We demonstrate FACTERA’s ability to rapidly identify breakpoint-resolution fusion events with high sensitivity and specificity in patients with non-small cell lung cancer, including novel rearrangements. We anticipate that FACTERA will be broadly applicable to the discovery and analysis of clinically relevant fusions from both targeted and genome-wide sequencing datasets.

Availability and implementation:  http://factera.stanford.edu.

Contact:  arasha@stanford.edu or diehn@stanford.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A novel feature-based approach to extract drug–drug interactions from biomedical text
Authors: Bui Quoc-Chinh , Sloot Peter M.A. , van Mulligen Erik M. , Kors Jan A.
Published: August 2014

Motivation: Knowledge of drug–drug interactions (DDIs) is crucial for health-care professionals to avoid adverse effects when co-administering drugs to patients. As most newly discovered DDIs are made available through scientific publications, automatic DDI extraction is highly relevant.

Results: We propose a novel feature-based approach to extract DDIs from text. Our approach consists of three steps. First, we apply text preprocessing to convert input sentences from a given dataset into structured representations. Second, we map each candidate DDI pair from that dataset into a suitable syntactic structure. Based on that, a novel set of features is used to generate feature vectors for these candidate DDI pairs. Third, the obtained feature vectors are used to train a support vector machine (SVM) classifier. When evaluated on two DDI extraction challenge test datasets from 2011 and 2013, our system achieves F-scores of 71.1% and 83.5%, respectively, outperforming any state-of-the-art DDI extraction system.

Availability and implementation: The source code is available for academic use at http://www.biosemantics.org/uploads/DDI.zip

Contact: q.bui@erasmusmc.nl
BioBloom tools: fast, accurate and memory-efficient host species sequence screening using bloom filters
Authors: Chu Justin , Sadeghi Sara , Raymond Anthony , Jackman Shaun D. , Nip Ka Ming , Mar Richard , Mohamadi Hamid , Butterfield Yaron S. , Robertson A. Gordon , Birol Inanç
Published: August 2014

Large datasets can be screened for sequences from a specific organism, quickly and with low memory requirements, by a data structure that supports time- and memory-efficient set membership queries. Bloom filters offer such queries but require that false positives be controlled. We present BioBloom Tools, a Bloom filter-based sequence-screening tool that is faster than BWA, Bowtie 2 (popular alignment algorithms) and FACS (a membership query algorithm). It delivers accuracies comparable with these tools, controls false positives and has low memory requirements.

Availability and implementaion:  www.bcgsc.ca/platform/bioinfo/software/biobloomtools

Contact:  cjustin@bcgsc.ca or ibirol@bcgsc.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
Liability of Foreignness in Historical Context: German Business in Preindependence India (1880–1940)
Authors: Lubinski Christina
Published: August 2014

Much of international business literature has dealt with the costs of engaging in business abroad. Recently, several authors have called into question the basic assumptions of the “liability of foreignness” argument. They plead for a more nuanced look at nationality beyond the dichotomy of foreign vis-à-vis local firms and raise doubts about the assumption that more distance necessarily translates into higher costs. This article adds to this criticism with a historical analysis of German multinational enterprises in preindependence India. The case proves (1) the relevance of specific nationalities, (2) the importance of conflicting host and home country attitudes for understanding multinationals’ strategy, and (3) the possibility of spillover effects across national borders. Expanding on existing theory, the article makes a point in showing how malleable and contextual associations with nationality are, thus making a thorough historical analysis of commercial, political, and cultural links between host and home country indispensable.
Evaluating the predictive performance of empirical estimators of natural mortality rate using information on over 200 fish species
Authors: Then Amy Y , Hoenig John M , Hall Norman G , Hewitt David A ,   Handling editor: Ernesto Jardim
Published: August 2014

Many methods have been developed in the last 70 years to predict the natural mortality rate, M, of a stock based on empirical evidence from comparative life history studies. These indirect or empirical methods are used in most stock assessments to (i) obtain estimates of M in the absence of direct information, (ii) check on the reasonableness of a direct estimate of M, (iii) examine the range of plausible M estimates for the stock under consideration, and (iv) define prior distributions for Bayesian analyses. The two most cited empirical methods have appeared in the literature over 2500 times to date. Despite the importance of these methods, there is no consensus in the literature on how well these methods work in terms of prediction error or how their performance may be ranked. We evaluate estimators based on various combinations of maximum age (tmax), growth parameters, and water temperature by seeing how well they reproduce >200 independent, direct estimates of M. We use tenfold cross-validation to estimate the prediction error of the estimators and to rank their performance. With updated and carefully reviewed data, we conclude that a tmax-based estimator performs the best among all estimators evaluated. The tmax-based estimators in turn perform better than the Alverson–Carney method based on tmax and the von Bertalanffy K coefficient, Pauly’s method based on growth parameters and water temperature and methods based just on K. It is possible to combine two independent methods by computing a weighted mean but the improvement over the tmax-based methods is slight. Based on cross-validation prediction error, model residual patterns, model parsimony, and biological considerations, we recommend the use of a tmax-based estimator (M=4.899tmax−0.916, prediction error = 0.32) when possible and a growth-based method (M=4.118K0.73L∞−0.33 , prediction error = 0.6, length in cm) otherwise.
Therapeutic uses of anti-interleukin-6 receptor antibody
Authors: Kang Sujin , Tanaka Toshio , Kishimoto Tadamitsu
Published: August 2014

Cytokine-targeted therapy has generated a paradigm shift in the treatment of several immune-mediated diseases. Interleukin-6 (IL-6), which was initially identified as B-cell stimulatory factor 2, is a prototypical cytokine with wide-ranging biological effects on immune cells such as B and T cells, on hepatocytes, hematopoietic cells, vascular endothelial cells and on many others. IL-6 is thus crucially involved in the regulation of immune responses, hematopoiesis and inflammation. When infections and tissue injuries occur, IL-6 is promptly synthesized and performs a protective role in host defense against such stresses and traumas. However, excessive production of IL-6 during this emergent process induces potentially fatal complications, including systemic inflammatory response syndrome (SIRS), and dysregulated, persistently high expression of IL-6 causes the onset or development of various chronic immune-mediated disorders. For these reasons, IL-6 blockade was expected to become a novel therapeutic strategy for various diseases characterized by IL-6 overproduction. Indeed, worldwide clinical trials of tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, have successfully proved its outstanding efficacy against rheumatoid arthritis, juvenile idiopathic arthritis and Castleman disease, leading to the approval of tocilizumab for the treatment of these diseases. Moreover, various reports regarding off-label use of tocilizumab strongly suggest that it will be widely applicable for acute, severe complications such as SIRS and cytokine-release syndrome and other refractory chronic immune-mediated diseases.
Lack of Awareness of Human Immunodeficiency Virus (HIV) Infection: Problems and Solutions With Self-reported HIV Serostatus of Men Who Have Sex With Men
Authors: Sanchez Travis H. , Kelley Colleen F. , Rosenberg Eli , Luisi Nicole , O'Hara Brandon , Lambert Rodriques , Coleman Raphael , Frew Paula , Salazar Laura F. , Tao Sijia , Clarke William , del Rio Carlos , Sullivan Patrick S.
Published: August 2014

Background.  Lack of human immunodeficiency virus (HIV) infection awareness may be a driver of racial disparities in HIV infection among men who have sex with men (MSM). Lack of awareness is typically measured by comparing HIV test result to self-reported HIV status. This measure may be subject to reporting bias and alternatives are needed.

Methods.  The InvolveMENt study examined HIV disparities between black and white MSM from Atlanta. Among HIV-positive participants who did not report knowing they were positive, we examined other measures of awareness: HIV viral load (VL) <1000 copies/mL (low VL), antiretroviral (ARV) drugs in blood, and previous HIV case surveillance report.

Results.  Using self-report only, 32% (62 of 192) of black and 16% (7 of 45) of white MSM were not aware of their HIV infection (P = .03). Using self-report and low VL, 25% (48 of 192) black and 16% (7 of 45) white MSM lacked awareness (P = .18). Using self-report and ARVs, 26% (50 of 192) black and 16% (7 of 45) white MSM lacked awareness (P = .14). Using self-report and surveillance report, 15% (28 of 192) black and 13% (6 of 45) white MSM lacked awareness (P = .83).

Conclusions.  Self-report only may overestimate true lack of awareness of HIV status for black MSM. If, as our data suggest, black MSM are not less likely to be aware of their HIV infection than are white MSM, then this factor is not a substantial driver of HIV disparity. Future HIV research that depends on accurate measurement of HIV status awareness should consider including additional laboratory and case surveillance data.
Safety and Efficacy Study of an Ozone Laser Combined Therapy Using Puncture Needle in the Treatment of Patients With Cervical Spondylosis
Authors: Gu Ke , Yan Yuqiu , Wei Wu , Li Yan , Liu Wenli , Guo Yang , Yu Long
Published: August 2014

Study Design and Methods:

Fifty-eight patients with cervical spondylosis (CS) were treated with patented technology of ozone laser combined therapy using puncture needle between August 2008 and February 2010. Visual Analogue Scale (VAS) score changes before and 6 months after surgery and MacNab score criteria 6 months after surgery were analyzed.

Background and Objective:

CS normally occurs over the age of 50 and broadly presents as either myelopathy or radiculopathy. Complementary treatment strategies have long been envisaged as a possible alternative in alleviating neck pain associated with CS; however, it is still in moderate use due to lack of adequate and convincing evidence of its safety and efficacy. The current study was to define and understand the therapeutic effects and safety of a newly developed patented technology, ozone, and laser via puncture needle, in the treatment of CS.

Results:

The VAS score of preoperative neck and shoulder pain was (6.57±1.34) scores, which decreased to 1.80±0.65 at 1-week postsurgery, and was completely alleviated by the end of 1 month (VAS score 0–2 after 1, 3, and 6 mo after surgery) (Kruskal-Wallis rank-sum test, H=1.680, P=0.000). VAS scores did not exhibit any significant rebound within 6 months after surgery (29 patients were excellent; 23 good; and 6 were fair, overall excellent, and good rate of 89.6%).

Conclusion:

Ozone and laser combined therapy via puncture needle for the treatment of CS is safe and effective.
Genome-based reclassification of Bacillus cibi as a later heterotypic synonym of Bacillus
indicus and emended description of Bacillus indicus
Authors: Stropko Samantha J. , Pipes Shannon E. , Newman Jeffrey D.
Published: August 2014

While characterizing a related strain, it was noted that there was little difference between the 16S rRNA gene sequences of

Bacillus indicus

LMG 22858T and

Bacillus cibi

DSM 16189T. Phenotypic characterization revealed differences only in the utilization of mannose and galactose and slight variation in pigmentation. Whole genome shotgun sequencing and comparative genomics were used to calculate established phylogenomic metrics and explain phenotypic differences. The full, genome-derived 16S rRNA gene sequences were 99.74 % similar. The average nucleotide identity (ANI) of the two strains was 98.0 %, the average amino acid identity (AAI) was 98.3 %, and the estimated DNA–DNA hybridization determined by the genome–genome distance calculator was 80.3 %. These values are higher than the species thresholds for these metrics, which are 95 %, 95 % and 70 %, respectively, suggesting that these two strains should be classified as members of the same species. We propose reclassification of

Bacillus cibi

as a later heterotypic synonym of

Bacillus indicus

and an emended description of

Bacillus indicus

.
Serological versus molecular typing of surface-associated immune evading polysaccharide antigens-based phenotypes of Staphylococcus aureus
Authors: Waryah Charlene B. , Gogoi-Tiwari Jully , Wells Kelsi , Costantino Paul , Al-Salami Hani , Sunagar Raju , Isloor Shrikrishna , Hegde Nagendra , Richmond Peter , Mukkur Trilochan
Published: August 2014

The aim of this study was to compare the performance of serological versus molecular typing methods to detect capsular polysaccharide (CP) and surface-associated polysaccharide antigen 336 phenotypes of Staphylococcus aureus isolates. Molecular typing of CP types 1, 5 and 8 was carried out using PCR, whereas serological typing of CP1, 2, 5, 8 and antigen 336 was carried out by slide agglutination using specific antisera. By genotyping, 14/31 strains were CP8 positive, 12/31 strains were CP5 and the remaining 6/31 isolates were non-typable (NT). One isolate was positive for both CP5 and CP8 by PCR, but was confirmed as CP8 type serologically. Detection of CP2 and type 336 by PCR was not possible because specific primers were either not available or non-specific. Using serotyping, 14/31 strains were CP8 positive, 11/31 CP5 positive and 2/31 positive for antigen 336. The remaining four S. aureus isolates were serologically NT. However, three of four NT and two 336-positive S. aureus isolates were encapsulated as determined by light microscopy after capsular staining. This discovery was surprising and warrants further investigations on the identification and characterization of additional capsular phenotypes prevalent among S. aureus clinical isolates. It was concluded that serological typing was a better method than molecular typing for use in epidemiological investigations based upon the distribution of surface-associated polysaccharide antigens-based phenotypes.
Multi-stress resistance in Lactococcus lactis is actually escape from purine-induced stress sensitivity
Authors: Ryssel Mia , Hviid Anne-Mette Meisner , Dawish Mohamed S. , Haaber Jakob , Hammer Karin , Martinussen Jan , Kilstrup Mogens
Published: August 2014

Multi-stress resistance is a widely documented and fascinating phenotype of lactococci where single mutations, preferentially in genes involved in nucleotide metabolism and phosphate uptake, result in elevated tolerance to multiple stresses simultaneously. In this report, we have analysed the metabolic basis behind this multi-stress-resistance phenotype in Lactococcus lactis subsp. cremoris MG1363 using acid stress as a model of multi-stress resistance. Surprisingly, we found that L. lactis MG1363 is fully resistant to pH 3.0 in the chemically defined SA medium, contrary to its sensitivity in the rich and complex M17 medium. When salvage of purines and subsequent conversion to GTP was permitted in various genetic backgrounds of L. lactis MG1363, the cells became sensitive to acid stress, indicating that an excess of guanine nucleotides induces stress sensitivity. The addition of phosphate to the acid-stress medium increased the stress sensitivity of L. lactis MG1363. It is also shown that high intracellular guanine nucleotide pools confer increased sensitivity to high temperatures, thus showing that it is indeed a multi-stress phenotype. Our analysis suggests that an increased level of guanine nucleotides is formed as a result of an improved conversion of guanosine in the salvage pathway. Based upon our findings, we suggest that L. lactis MG1363 is naturally multi-stress resistant in habitats devoid of any purine source. However, any exogenous purine that results in increased guanine nucleotide pools renders the bacterium sensitive to environmental stresses.