bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta Decay Redux, Slow Neutrons, Bohr and his Realm
Authors: Stuewer Roger H.
Published: September 2018

A large conference on nuclear physics was held in London and Cambridge from October 1–6, 1934. Six German refugee physicists were present, but Werner Heisenberg was not. Czech theoretical physicists Guido Beck and Kurt Sitte had proposed a theory of beta decay that challenged Fermi’s, which Beck presented but apparently gained no support for. On October 22, Fermi serendipitously discovered the efficaciousness of slow neutrons in producing nuclear reactions. Niels Bohr would be the greatest beneficiary of Fermi’s discovery. In 1935 Bohr, with the assistance of refugee Otto Robert Frisch, began to develop experimental nuclear physics at his institute, which after its inauguration in 1920 became a mecca for young physicists. On September 29, 1943, Bohr and his family were among the 7220 Danish and other Jews who were transported to Sweden in the greatest mass rescue operation of the war.
Political Practices and Political Community in the Early Republic, 1790–1794
Authors: Owen Kenneth
Published: September 2018

The ratification of the US Constitution forced Pennsylvanians to adapt their democratic, extra-governmental political practices to the new federal government. This chapter looks at how these practices evolved in the early 1790s, investigating gubernatorial and legislative elections, as well as the creation of Democratic-Republican Societies and the Whiskey Rebellion of 1794. These activities focused on opposing the actions of George Washington’s administration, defending popular political activity against the Federalist policies including Alexander Hamilton’s excise tax on whiskey. The chapter particularly focuses on the events of the Whiskey Rebellion, looking at how Pennsylvanians from all corners of the state developed political institutions as they sought to resolve the long-running tensions which led to violence. Ultimately, the resolution of the Whiskey Rebellion vindicated a vision of popular sovereignty in which non-violent, representative political action, rather than an appeal to federal authority, proved most successful.
Possible Patterns
Authors: Russell Jeffrey Sanford , Hawthorne John
Published: September 2018

“There are no gaps in logical space,” writes Lewis (1986), giving voice to sentiment shared by many philosophers. But different natural ways of trying to make this sentiment precise turn out to conflict with one another. One is a pattern idea: “Any pattern of instantiation is metaphysically possible.” Another is a cut and paste idea: “For any objects in any worlds, there exists a world that contains any number of duplicates of all of those objects.” Jumping off from discussions from Forrest and Armstrong (1984) and Nolan (1996), the authors use resources from model theory to show the inconsistency of certain packages of combinatorial principles and the consistency of others.
‘Never such Innocence’
Authors: Scott Charlotte
Published: September 2018

This chapter focuses on the history plays. Ascertaining the dominant ways in which the child becomes a demonstrative figure of legacy, responsibility, and failure, Chapter 2 explores the prevalence of young children in Shakespeare’s chronicle history. Focusing on the diminutive figure of the child, this chapter examines how the idea of ‘littleness’ drives the representation of children as innocent, vulnerable, and emotive. Discussing how Shakespeare exploits as well as challenges contemporary and Christian symbols of childhood, the history plays demonstrate a profound investment in the figure of the child as an image of historical responsibility. Beginning with Richard III, this chapter explores the theatrical power of infanticide and the strategic ways in which children disrupt the playing spaces, from the interruption of an aside to the production of emotional affect; the chapter assesses early modern expectations of childhood and the competing ways in which children are presented as distinct from the adult world.
‘Prevent it, resist it, let it not be so, | Lest child, child’s children, cry against you woe!’
Authors: Scott Charlotte
Published: September 2018

The final chapter offers a conclusion through a reflection on some of the major concerns of the book. Centrally, this chapter returns to the figure of the child and its affective presence on stage, the early modern contexts through which children were both celebrated and disenfranchised, and the unique position that Shakespeare takes in supporting and developing their role on the early modern stage. The book demonstrates that the child was a vital figure in the development of early modern drama, not through their presentation in children’s playing companies but through the plays’ exploration of what children mean to those who love them, as well as those who destroy them. Considering the shape of history, the images of responsibility through which societies organize their value systems, the structures of power and responsibility through which parents determine both their love and their separation, the book concludes with the feelings that shape the children of the past, whether recollected in tranquillity or violence.
Well-Being and Ethical Virtue
Authors: Kraut Richard
Published: September 2018

A method for studying well-being is proposed, one that makes room for philosophical theorizing and for the test of introspection. The method is used to support the intrinsic value of philosophy, the sciences, the arts, and other activities that deepen and enrich our experience. These undertakings are various forms of human flourishing: they make use of our natural powers, bringing them to a high point of development. One especially important form of human flourishing occurs in ethical life: the inner life of a good person is a component of well-being available to nearly every human being. The Kantian tradition distorts the nature of ethical life by neglecting self-interested reasons for having and exercising the moral virtues.
Experientialism and the Experience Machine
Authors: Kraut Richard
Published: September 2018

Nozick’s thought experiment makes many assumptions about the experience machine that require re-examination. It raises questions about whether illusion and self-deception are inherently bad; about what it is to be active rather than passive; about what it is to be free; about the value of physical embodiment and causal interaction with the material world; about the value of fiction and beauty; and about solipsism. Would one’s life be bad, if there are no other minds? Posthumous harms and benefits are also thought to pose a problem for an experientialist conception of well-being. Aristotle wrongly believes that there are such harms and benefits, but his error is negligible, because he assigns them minor importance.
Hegel’s Methodology
Authors: Stewart Jon
Published: September 2018

Chapter 1 gives an account of the methodology and organization of Hegel’s Lectures on the Philosophy of Religion. He wishes to restore religion to its proper position by restoring the traditional doctrines of Christianity. But to do this it is necessary to see how the conception of the divine has developed historically through the different world religions. Hegel wishes to show that the general state of a given culture or people can be seen reflected in its conception of the divine. Thus, he can trace the development of human culture or “spirit” through history by analyzing the different world religions. Finally, an account is given of the rise of Orientalism in Europe during Hegel’s time and its influence on his thinking.
Roman Polytheism
Authors: Stewart Jon
Published: September 2018

Hegel notes that it has been traditional to treat Greek and Roman religion together since there seems to be a general correspondence among their divinities. But in fact, he claims, they represent two quite different general conceptions. Since the Romans and the Greeks had such different political developments, their cultures and religions are fundamentally distinct. The Roman gods are associated with numerous fixed goals or purposes. Hegel takes this to be an important point of contrast with the Greek religion. For the Greeks, the individual gods had a variety of individual powers and characteristics, but they were never fixed to their goals or ends in a dogged way. The Greek gods can be fickle, changing their minds just as humans tend to do. But the Roman gods are one-dimensional since they are fixed on a single end and are not anything more complex than this end.
The Nonadaptive Forces of Evolution
Authors: Walsh Bruce , Lynch Michael
Published: September 2018

This chapter examines the relative strengths of the nonadaptive evolutionary forces (drift, mutation, recombination) acting on genomes. It reviews estimators for effective population size, mutation rate, and recombination rate, and summarizes the known genomic results over a wide range of taxa. The mutation rate tends to be lower in organisms with larger effective population sizes, consistent with the drift-barrier hypothesis wherein selection is ineffective when it is less than the reciprocal of the effective population size.
Analysis of Short-term Selection Experiments: 2. Mixed-model and Bayesian Approaches
Authors: Walsh Bruce , Lynch Michael
Published: September 2018

When the full pedigree of individuals whose values (records) were used in the selection decisions during an experiment (or breeding program) is known, LS analysis can be replaced by mixed models and their Bayesian extensions. In this setting, REML can be used to estimate genetic variances and BLUP can be used to estimate the mean breeding value in any given generation. The latter allows for genetic trends to be separated from environmental trends without the need for a control population. Under the infinitesimal model setting (wherein selection-induced allele-frequency changes are small during the course of the experiment), the use of the relationship matrix in a BLUP analysis accounts for drift, nonrandom mating, and linkage disequilibrium.
Associative Effects: Competition, Social Interactions, Group and Kin Selection
Authors: Walsh Bruce , Lynch Michael
Published: September 2018

The phenotypes of those individuals with which an focal individual interacts often influences the trait value in the focal individual. Maternal effects is a classic example of this phenomena, as is fitness. If these traits are heritable, then the selection response depends on both the change in the direct effects influencing a target trait and the associative effects contributed by interacting individuals. In such a setting, the breeder's equation no longer holds, as the problem is now a multiple trait one. This chapter examines the theory of response under models with both direct and associative effects, which can lead to a reversed response (a trait selected to increase instead decreases). The evolution of behavioral traits, including the evolution of altruism, is best handled using this approach. Further, kin and group selection follow as special cases of the gerenal model under multilevel selection. This chapter also examines how mixed models can be used estimate model parameters.
Long-term Response: 3. Adaptive Walks
Authors: Walsh Bruce , Lynch Michael
Published: September 2018

One model for long-term evolution is an adaptive walk, a series of fixations of mutations that moves the trait mean toward some optimal value. The foundation for this idea traces back to Fisher's geometric model, which showed that mutations of large effect are favored when a trait is far from its optimal, while smaller effects are favored as it approaches the optimal value. Under fairly general conditions, this results in a roughly exponential distribution of fixed adaptive effects. An alternative to trait-based walks are walks in fitness space, motivated by considering a series of mutations to improve the fitness of a particular sequence. In such settings, extreme value theory also suggests a roughly exponential distribution, now of fitness (instead of trait) effects, for mutations fixed during the walk. Much of this theory offers at least partial experimental testing, and this chapter describes not only the theory, but also some of the empirical work testing the models.
Individual Fitness and the Measurement of Univariate Selection
Authors: Walsh Bruce , Lynch Michael
Published: September 2018

This chapter examines various estimates of the fitness of an individual, focusing on statistical issues and potential sources of bias. With estimates of individual fitness in hand, one can then search for fitness-trait association, and this topic comprises the second half of the chapter. A number of metrics for describing how the phenotypic distribution of a trait is perturbed by selection are examined, again along with a discussion of statistical issues and sources of bias.
Measuring Multivariate Selection
Authors: Walsh Bruce , Lynch Michael
Published: September 2018

This chapter extends many of the results from Chapter 29 on single trait-fitness associations to the multiple trait setting. It examines the estimate of multivariate fitness surfaces, starting with quadratic surfaces and then moving to nonparametric versions (which assume no a prior functional form). It also examines path analysis, the analysis of missing data, and multilevel selection.
Congruence and Representation
Authors: Dalton Russell J.
Published: September 2018

This chapter examines the congruence between voters and their preferred party on the economic and cultural cleavages. It describes political representation on both cleavages at the macro and micro levels. The chapter determines whether voters as a collective find a party that well represents their positions, or if they satisfice with a party that only partially reflects their views. There is a very close collective fit between voters and their chosen party in the two-dimensional space. Then the chapter examines the fit between voter and party for each individual voter. While there is strong voter-party congruence at the macro level, this relationship weakens at the micro level. This produces a tension between collective representation and individual-level views of representation.
The Return of Orpheus
Authors: Heslin Peter J.
Published: September 2018

Propertius’ second book is in two ways a response to the Georgics. From its opening poem, it responds to Virgil’s declaration of intent to write an epic for Octavian; and that polemic continues to be couched primarily in mythological terms. At the same time, Propertius responds in a variety of ways to Virgil’s Orpheus as a representation of the tragic, solipsistic love-poet. Propertius’ Orpheus behaves rather differently. Propertius does not deny the tragedy of Cornelius Gallus; he refigures him not as Orpheus but as Adonis, who must die but is eternally reborn.
Herder's Philosophy
Authors: Forster Michael N.
Published: September 2018

This book considers Herder’s philosophy in the round and argues that it is both far more impressive in quality and far more influential in modern thought than has previously been realized. After an introduction on Herder’s intellectual biography, philosophical style, and general program in philosophy, there are chapters on his philosophy of language, his hermeneutics, his theory of translation, his contribution of the philosophical foundations for both linguistics and cultural anthropology, his philosophy of mind, his aesthetics, his moral philosophy, his philosophy of history, his political philosophy, his philosophy of religion, and his intellectual influence. The book argues that he contributed vitally important ideas in all of these areas; that in many of them his ideas were seminal for subsequent philosophers, including Friedrich Schlegel, Schleiermacher, Wilhelm von Humboldt, Hegel, and Nietzsche; that they indeed founded whole new disciplines, such as linguistics, anthropology, and comparative literature; and that moreover they were in many cases even better than what these subsequent thinkers and disciplines went on to make of them.
Philosophy of Mind
Authors: Forster Michael N.
Published: September 2018

Herder developed a very powerful and influential philosophy of mind. He was the source of Hegel’s famous threefold distinction between subjective, objective, and absolute mind (or Geist). Concerning the fundamental mind–body question he wavered between neutral monism and materialism, but developed a theory that has marked advantages over rival theories such as dualism, mind–brain identity, and behaviorism. Accordingly, he also developed a naturalized reconception of immortality. He also worked out an important theory of the unity of the mind’s faculties. In addition, he argued both that minds are fundamentally social and that they nonetheless include individuality. And finally, he developed a rich and original theory of the unconscious. These positions are not only of great intrinsic value, but also exercised a powerful influence on successors such as Hegel, Schleiermacher, and Nietzsche.
Shape Reconstructions from Small Angle Scattering Data
Authors: Lattman Eaton E. , Grant Thomas D. , Snell Edward H.
Published: September 2018

This chapter discusses recovering shape or structural information from SAXS data. Key to any such process is the ability to generate a calculated intensity from a model, and to compare this curve with the experimental one. Models for the particle scattering density can be approximated as pure homogenenous geometric shapes. More complex particle surfaces can be represented by spherical harmonics or by a set of close-packed beads. Sometimes structural information is known for components of a particle. Rigid body modeling attempts to rotate and translate structures relative to one another, such that the resulting scattering profile calculated from the model agrees with the experimental SAXS data. More advanced hybrid modelling procedures aim to incorporate as much structural information as is available, including modelling protein dynamics. Solutions may not always contain a homogeneous set of particles. A common case is the presence of two or more conformations of a single particle or a mixture of oligomeric species. The method of singular value decomposition can extract scattering for conformationally distinct species.
Distinct Instrumental Approaches to SAXS
Authors: Lattman Eaton E. , Grant Thomas D. , Snell Edward H.
Published: September 2018

There are more specialized applications of SAXS and SANS which require specific experimental considerations. This chapter covers size exclusion chromatography which has proven to be useful to study both soluble and membrane bound proteins allowing the study of samples that show time and concentration dependent dynamics. It also describes iime-resolved techniques for SAXS and in a few cases, SANS. Finally, with improved X-ray sources, detectors, sample handling, and compute power, the ability to perform SAXS data in high-throughput is available. This is discussed in enabling the use of SAXS to study protein interactions, map macromolecular conformation, and rapidly characterize samples amongst other applications.
Examples of Biological Small Angle Scattering
Authors: Lattman Eaton E. , Grant Thomas D. , Snell Edward H.
Published: September 2018

In this chapter we illustrate the biological applications of small angle scattering. We cover examples of contrast matching has been used in the neutron case and with SAXS,. time-resolved studies that have helped reveal mechanism and how SAXS or SANS as a solution technique can access information missing from other studies, in particular residues that may be crystallographically undefined. We show examples of puting known structural information in context, and following large-scale functional changes or show when distinct populations co-exist in solution. The list of examples provided is not exhaustive and should be seen as a glimpse of the potential of biological mechanisms where SAXS or SANS can provide unique information complementary to other methods and help define function and mechanism.
Aposematism
Authors: Ruxton Graeme D. , Allen William L. , Sherratt Thomas N. , Speed Michael P.
Published: September 2018

Aposematism is the pairing of two kinds of defensive phenotype: an often repellent secondary defence that typically renders prey unprofitable to predators if they attack them and some evolved signal that indicates the presence of that defence. Aposematic signals often work to modify the behaviours of predators both before and during attacks. Warning coloration, for example, may increase wariness and hence improve the chances that a chemically defended prey is released unharmed after an attack. An aposematic signal may therefore first tend to reduce the probability that a predator commences attack (a primary defence) and then (as a component of secondary defence) reduce the probability that the prey is injured or killed during any subsequent attack. In this chapter we will consider both the primary and the secondary effects of aposematic signals on prey protection. We begin first by describing the common features of aposematic signals and attempting to show the wide use to which aposematic signalling is deployed across animals (and perhaps plants too). We then review the interesting evolutionary issues aposematic signals raise, including their initial evolution and their integration with sexual and other signals. We also discuss important ecological, co-evolutionary, and macroevolutionary consequences of aposematism.
Every Home’s a First Night
Authors: Maslon Laurence
Published: September 2018

The technological advance of the long-playing record allowed up to 45 minutes of a Broadway score to be heard by home listeners; this innovation intersected with the increased narrative imperatives of the post-Oklahoma! musical and forever changed what a cast album could accomplish. The commodity of the cast album exploded in homes across America as RCA Victor, Decca, Capitol, and Columbia Records all vied for the trophy of recording a Broadway show, setting up an arena of intense competition. The Columbia recordings of both Kiss Me, Kate and South Pacific on the brand-new LP format in the late 1940s essentially sold the new format to American consumers.
A Few of My Favorite Things
Authors: Maslon Laurence
Published: September 2018

The technology to reproduce a film’s soundtrack for home consumption didn’t arrive fully until the early 1950s; it was no surprise that the Capitol soundtrack recording to the 1955 film of Oklahoma! was the biggest seller of its day. Film soundtracks gave home listeners a second chance to hear their favorite scores and often, as in the case of West Side Story, the film soundtrack provided a new opportunity to discover the music (that soundtrack stayed longer at No. 1 than any album in history to this day). The performer who sold more soundtrack albums than anyone else in the 1960s was Julie Andrews, whose simultaneous recordings of the films Mary Poppins and The Sound of Music made her the most ubiquitous singer in pop culture.
Intersectionality in American Sign Language Hip Hop Interpreting
Authors: Marrero Elyse
Published: September 2018

Viral videos of American Sign Language (ASL) hip hop interpreters at music festivals have circulated the online mediascape, bringing attention to music interpreting, ASL, and Deaf culture. Hip hop interpreters create intersectional embodied texts challenging our assumed ideas of hip hop, Black masculinity, white femininity, and the connections between ASL, music, and Deaf people. Many hip hop interpreters are white women, which creates an interesting dynamic between interpreter and musical artist, specifically how both parties intersect and meet through their own expressions of hip hop music and culture. Using the concept of dialogical performance, this chapter provides textual analyses of a televised “sign language rap battle” and ASL interpretations of Kendrick Lamar’s “Swimming Pools” and Wiz Khalifa’s “Black and Yellow.” An interpreter’s presence, and how she adds news layers of meaning to a song and to her identity in relation to a song and performance, is explored in each presented scenario.
Parental Autonomy, Children with Disabilities, and Horizontal Identities
Authors: Crossley Mary
Published: September 2018

Ordinarily, parents have broad authority to make medical decisions for their children. This chapter explores whether a child’s disability may sometimes provide a basis for deviating from the legal presumption of parental authority. Drawing on the concept of “horizontal identities” and highlighting the potential roles of disability bias and conflicts of interest, the chapter examines how several concerns may undermine justifications for parental authority to pursue elective medical interventions for their disabled children. After arguing that the presence of several of these concerns in a particular case justifies skepticism regarding the parents’ unfettered discretion to pursue elective interventions, the chapter suggests some ways that parental authority might be constrained or guided in such cases.
Video-Game–Based Exercises for Older People With Chronic Low Back Pain: A Randomized Controlledtable Trial (GAMEBACK)
Authors: Zadro Joshua R , Shirley Debra , Simic Milena , Mousavi Seyed J , Ceprnja Dragana , Maka Katherine , Sung Jennie , Ferreira Paulo
Published: September 2018

Background

Video game technology increases adherence to home exercise and could support self-management for older people with chronic low back pain (LBP).

Objective

The objective was to investigate the effects of home-based video game exercises on pain self-efficacy and care-seeking in older people with chronic LBP.

Design

The study was a randomized controlled trial.

Setting

The setting was a community and waiting list.

Participants

Sixty participants, aged > 55 years with chronic LBP, were randomized (1:1) to Wii Fit U exercises or to continue their usual activities for 8 weeks.

Intervention

The intervention was home-based Wii Fit U flexibility, strengthening, and aerobic exercises for 60 minutes, 3 times per week, with fortnightly calls from a physical therapist.

Measurements

Measurements included pain self-efficacy and care-seeking (primary outcomes), and physical activity, pain, function, disability, fear of movement/reinjury, falls efficacy, recruitment and response rates, adherence, experience with the intervention, and adverse events (secondary outcomes).

Results

The mean age of participants was 67.8 (standard deviation = 6.0) years. Adherence to the total recommended exercise time was 70.8%, and no adverse events were reported. Participants completing Wii Fit U exercises had significantly higher pain self-efficacy at 6 months, but not immediately postintervention or at 3 months; there were no between-group differences in care-seeking. Compared with the control group, participants completing Wii Fit U exercises demonstrated significantly greater improvements in pain and function at 8 weeks and were more likely to engage in flexibility exercises at 6 months. There were no significant between-group differences for the remaining outcomes.

Limitations

Participants and therapists were not blinded.

Conclusions

Wii Fit U exercises improved pain self-efficacy at 6 months, and pain and function immediately postintervention in older people with chronic LBP, but the clinical importance of these changes is questionable. Wii Fit U exercises had no effect on care-seeking, physical activity, disability, fear of movement/reinjury, or falls efficacy.
Addressing Ill Health: Sickness and Retirement in the Victorian Post Office
Authors: Green David R , Brown Douglas H L , McIlvenna Kathleen
Published: September 2018

This article explores ill health and retirement in the Victorian Post Office. Compared to other branches of the Civil Service, ill health was of greater importance as a cause of retirement. Post Office doctors kept careful records of sickness absence, which rose over the period for all workers. These records were also used to determine if employees should be pensioned off on grounds of ill health. Employees in different sections of the Post Office experienced varying levels of sickness depending on their place of employment and the type of work undertaken. Feminisation of the workforce also affected the prevalence of sickness absences, especially in London. Place of work was an important influence on the pattern of sickness with urban areas having higher levels of sickness than rural districts, with distinct sets of conditions linked to each.
Inoculation Method Impacts Symptom Development Associated with Diaporthe aspalathi, D. caulivora, and D. longicolla on Soybean (Glycine max)
Authors: Ghimire Krishna , Petrović Kristina , Kontz Brian J. , Bradley Carl A. , Chilvers Martin I. , Mueller Daren S. , Smith Damon L. , Wise Kiersten A. , Mathew Febina M.
Published: September 2018

One hundred fifty-two Diaporthe isolates were recovered from symptomatic soybean (Glycine max) stems sampled from the U.S. states of Iowa, Indiana, Kentucky, Michigan, and South Dakota. Using morphology and DNA sequencing, isolates were identified as D. aspalathi (8.6%), D. caulivora (24.3%), and D. longicolla (67.1%). Aggressiveness of five isolates each of the three pathogens was studied on cultivars Hawkeye (D. caulivora and D. longicolla) and Bragg (D. aspalathi) using toothpick, stem-wound, mycelium contact, and spore injection inoculation methods in the greenhouse. For D. aspalathi, methods significantly affected disease severity (P < 0.001) and pathogen recovery (P < 0.001). The relative treatment effects (RTE) of stem-wound and toothpick methods were significantly greater than for the other methods. For D. caulivora and D. longicolla, a significant isolate × method interaction affected disease severity (P < 0.05) and pathogen recovery (P < 0.001). Significant differences in RTEs were observed among D. caulivora and D. longicolla isolates only when the stem-wound and toothpick methods were used. Our study has determined that the stem-wound and toothpick methods are reliable to evaluate the three pathogens; however, the significant isolate × method interactions for D. caulivora and D. longicolla indicate that multiple isolates should also be considered for future pathogenicity studies.
The Horton–Rogers–Lapwood problem for an inclined porous layer with permeable boundaries
Authors: Barletta A. , Celli M.
Published: September 2018

A formulation of the Horton–Rogers–Lapwood problem for a porous layer inclined with respect to the horizontal and characterized by permeable (isobaric) boundary conditions is presented. This formulation allows one to recover the results reported in the literature for the limiting cases of horizontal and vertical layer. It is shown that a threshold inclination angle exists which yields an upper bound to a parametric domain where the critical wavenumber is zero. Within this domain, the critical Darcy–Rayleigh number can be determined analytically. The stability analysis is performed for linear perturbations. The solution is found numerically, for the inclination angles above the threshold, by employing a Runge–Kutta method coupled with the shooting method.
Robust data-driven discovery of governing physical laws with error bars
Authors: Zhang Sheng , Lin Guang
Published: September 2018

Discovering governing physical laws from noisy data is a grand challenge in many science and engineering research areas. We present a new approach to data-driven discovery of ordinary differential equations (ODEs) and partial differential equations (PDEs), in explicit or implicit form. We demonstrate our approach on a wide range of problems, including shallow water equations and Navier–Stokes equations. The key idea is to select candidate terms for the underlying equations using dimensional analysis, and to approximate the weights of the terms with error bars using our threshold sparse Bayesian regression. This new algorithm employs Bayesian inference to tune the hyperparameters automatically. Our approach is effective, robust and able to quantify uncertainties by providing an error bar for each discovered candidate equation. The effectiveness of our algorithm is demonstrated through a collection of classical ODEs and PDEs. Numerical experiments demonstrate the robustness of our algorithm with respect to noisy data and its ability to discover various candidate equations with error bars that represent the quantified uncertainties. Detailed comparisons with the sequential threshold least-squares algorithm and the lasso algorithm are studied from noisy time-series measurements and indicate that the proposed method provides more robust and accurate results. In addition, the data-driven prediction of dynamics with error bars using discovered governing physical laws is more accurate and robust than classical polynomial regressions.
The ecology of movement and behaviour: a saturated tripartite network for describing animal contacts
Authors: Manlove Kezia , Aiello Christina , Sah Pratha , Cummins Bree , Hudson Peter J. , Cross Paul C.
Published: September 2018

Ecologists regularly use animal contact networks to describe interactions underlying pathogen transmission, gene flow, and information transfer. However, empirical descriptions of contact often overlook some features of individual movement, and decisions about what kind of network to use in a particular setting are commonly
ad hoc
. Here, we relate individual movement trajectories to contact networks through a tripartite network model of individual, space, and time nodes. Most networks used in animal contact studies (e.g. individual association networks, home range overlap networks, and spatial networks) are simplifications of this tripartite model. The tripartite structure can incorporate a broad suite of alternative ecological metrics like home range sizes and patch occupancy patterns into inferences about contact network metrics such as modularity and degree distribution. We demonstrate the model's utility with two simulation studies using alternative forms of ecological data to constrain the tripartite network's structure and inform expectations about the harder-to-measure metrics related to contact.
MinION nanopore sequencing identifies the position and structure of bacterial antibiotic resistance determinants in a multidrug-resistant strain of enteroaggregative Escherichia coli
Authors: Greig David R. , Dallman Timothy J. , Hopkins Katie L. , Jenkins Claire
Published: September 2018

The aim of this study was to use single-molecule, nanopore sequencing to explore the genomic environment of the resistance determinants in a multidrug-resistant (MDR) strain of enteroaggregative Escherichia coli serotype O51 : H30, sequence type (ST) 38. Sequencing was performed on the MinION Flow cell MIN-106 R9.4. Nanopore raw FAST5 reads were base-called using Albacore v1.2.1, converted to FASTA and FASTQ formats using Poretools v0.6.0, and assembled using Unicycler v0.4.2, combining the long-read sequencing data with short-read data produced by Illumina sequencing. The genome was interrogated against an antimicrobial resistance (AMR) gene reference database using blast. The majority of the 12 AMR determinants identified were clustered together on the chromosome at three separate locations flanked by integrases and/or insertion elements [region 1 –catA, bla
OXA-1, aac(6′)-Ib-cr, tetA and bla
CTX-M-15; region 2 – dfrA1 and aadA1; region 3 – catA, bla
TEM-1, tetA and sul2]. AMR determinants located outside these three regions were a chromosomally encoded bla
CMY-16, mutations in gyrA and parC, and two plasmid-encoded AMR determinants, bla
OXA-181 and qnrS1 located on the same IncX3 plasmid. Long-read analysis of whole genome sequencing data identified mobile genetic elements on which AMR determinants were located and revealed the combination of different AMR determinants co-located on the same mobile element. These data contribute to a better understanding of the transmission of co-located AMR determinants in MDR E. coli causing gastrointestinal and extra-intestinal infections.
A novel core genome approach to enable prospective and dynamic monitoring of infectious outbreaks
Authors: van Aggelen Helen , Kolde Raivo , Chamarthi Hareesh , Loving Joshua , Fan Yu , Fallon John T. , Huang Weihua , Wang Guiqing , Fortunato-Habib Mary M. , Carmona Juan J. , Gross Brian D.
Published: September 2018

Whole-genome sequencing is increasingly adopted in clinical settings to identify pathogen transmissions. Currently, such studies are performed largely retrospectively, but to be actionable they need to be carried out prospectively, in which samples are continuously added and compared to previous samples. To enable prospective pathogen comparison, genomic relatedness metrics based on single nucleotide differences must be consistent across time, efficient to compute and reliable for a large variety of samples. The choice of genomic regions to compare, i.e., the core genome, is critical to obtain a good metric.

We propose a novel core genome method that selects conserved sequences in the reference genome by comparing its k-mer content to that of publicly available genome assemblies. The conserved-sequence genome is sample set-independent, which enables prospective pathogen monitoring. Based on clinical data sets of 3436 S. aureus, 1362 K. pneumoniae and 348 E. faecium samples, we show that the conserved-sequence genome disambiguates same-patient samples better than a core genome consisting of conserved genes. The conserved-sequence genome confirms outbreak samples with high accuracy: in a set of 2335 S. aureus samples, it correctly identifies 44 out of 45 outbreak samples, whereas the conserved gene method confirms 38 out of 45 outbreak samples.
rMETL: sensitive mobile element insertion detection with long read realignment
Authors: Jiang Tao , Liu Bo , Wang Yadong
Published: September 2018

Mobile element insertion (MEI) is a major category of structure variations (SVs). The rapid development of long read sequencing provides the opportunity to sensitively discover MEIs. However, the signals of MEIs implied by noisy long reads are highly complex, due to the repetitiveness of mobile elements as well as the serious sequencing errors. Herein, we propose Realignment-based Mobile Element insertion detection Tool for Long read (rMETL). rMETL takes advantage of its novel chimeric read re-alignment approach to well handle complex MEI signals. Benchmarking results on simulated and real datasets demonstrated that rMETL has the ability to more sensitivity discover MEIs as well as prevent false positives. It is suited to produce high quality MEI callsets in many genomics studies.

Availability and Implementation: rMETL is available from https://github.com/hitbc/rMETL.

Contact:ydwang@hit.edu.cn

Supplementary information: Supplementary data are available at Bioinformatics online.
Theta-Gamma Cascades and Running Speed
Authors: Sheremet A. , Kennedy J.P. , Qin Y. , Zhou Y. , Lovett S.D. , Burke S.N. , Maurer A. P.
Published: September 2018

The local field potentials (LFPs) of the hippocampus are primarily generated by the spatiotemporal accretion of electrical currents via activated synapses. Oscillations in the hippocampal LFP at theta and gamma frequencies are prominent during awake-behavior and have demonstrated several behavioral correlates. In particular, both oscillations have been observed to increase in amplitude and frequency as a function of running velocity. Previous investigations, however, have examined the relationship between velocity and each of these oscillation bands separately. Based on energy cascade models where “…perturbations of slow frequencies cause a cascade of energy dissipation at all frequency scales” (Buzsaki 2006), we hypothesized that the cross-frequency interactions between theta and gamma should increase as a function of velocity. We examined these relationships across multiple layers of the CA1 subregion and found a reliable correlation between the power of theta and the power of gamma, indicative of an amplitude-amplitude relationship. Moreover, there was an increase in the coherence between the power of gamma and the phase of theta, demonstrating increased phase-amplitude coupling with velocity. Finally, at higher velocities, phase entrainment between theta and gamma becomes stronger. These results have important implications and provide new insights regarding how theta and gamma are integrated for neuronal circuit dynamics, with coupling strength determined by the excitatory drive within the hippocampus.
Non-neutral evolution of H3.3-encoding genes occurs without alterations in protein sequence
Authors: Muhire Brejnev M. , Booker Matthew A. , Tolstorukov Michael Y.
Published: September 2018

Histone H3.3 is a developmentally essential variant encoded by two independent genes in human (H3F3A and H3F3B). While this two-gene arrangement is evolutionarily conserved, its origins and function remain unknown. Phylogenetics, synteny and gene structure analyses of the H3.3 genes from 32 metazoan genomes indicate independent evolutionary paths for H3F3A and H3F3B. While H3F3B bears similarities with H3.3 genes in distant organisms and with canonical H3 genes, H3F3A is sarcopterygian-specific and evolves under strong purifying selection. Additionally, H3F3B codon-usage preferences resemble those of broadly expressed genes and ‘cell differentiation-induced’ genes, while codon-usage of H3F3A resembles that of ‘cell proliferation-induced’ genes. We infer that H3F3B is more similar to the ancestral H3.3 gene and likely evolutionarily adapted for broad expression pattern in diverse cellular programs, while H3F3A adapted for a subset of gene expression programs. Thus, the arrangement of two independent H3.3 genes facilitates fine-tuning of H3.3 expression across cellular programs.
Molecular measurable residual disease testing of blood during AML cytotoxic therapy for early prediction of clinical response
Authors: Wong Hong Yuen , Sung Anthony D. , Lindblad Katherine E. , Sheela Sheenu , Roloff Gregory W. , Rizzieri David , Goswami Meghali , Mulé Matthew P. , Ramos Nestor R. , Tang Jingrong , Thompson Julie , DeStefano Christin B. , Romero Kristi , Dillon Laura W. , Kim Dong-Yun , Lai Catherine , Hourigan Christopher S.
Published: September 2018

PURPOSE

Measurable residual disease (MRD) testing after initial chemotherapy treatment can predict relapse and survival in AML. However, it has not been established if repeat molecular or genetic testing during chemotherapy can offer information regarding the chemotherapy sensitivity of the leukemic clone.

PATIENTS AND METHODS

Blood from 45 adult AML patients at day 1 and 4 of induction (n = 35) or salvage (n = 10) cytotoxic chemotherapy was collected for both quantitative real-time PCR (qPCR) assessment (WT1) and next generation sequencing (NGS, >500x depth) of 49 gene regions recurrently mutated in MDS/AML.

RESULTS

The median age was 62 (23-78); 42% achieved a complete response.WT1was overexpressed in most patients tested but was uninformative for very early MRD assessment. A median of 4 non-synonymous variants (range 0-7) were detected by DNA sequencing of blood on day 1 of therapy (median VAF: 29%). Only two patients had no variants detectable. All mutations remained detectable in blood on day 4 of intensive chemotherapy and remarkably the ratio of mutated to wild-type sequence was often maintained. This phenomenon was not limited to variants inDNMT3A, TET2andASXL1. The kinetics ofNPM1andTP53variant burden early during chemotherapy appeared to be exceptions and exhibited consistent trends in this cohort.

CONCLUSIONS

Molecular testing of blood on day 4 of chemotherapy is not predictive of clinical response in AML. The observed stability in variant allele frequency suggests that cytotoxic therapy may have a limited therapeutic index for clones circulating in blood containing these mutations. Further validation is required to confirm the utility of monitoringNPM1andTP53kinetics in blood during cytotoxic therapy.
Cohort Profile: Extended Cohort for E-health, Environment and DNA (EXCEED)
Authors: John Catherine , Reeve Nicola F , Free Robert C , Williams Alexander T , Farmaki Aliki-Eleni , Bethea Jane , Barton Linda M , Shrine Nick , Batini Chiara , Packer Richard , Terry Sarah , Hargadon Beverley , Wang Qingning , Melbourne Carl A , Adams Emma L , Bee Catherine E , Harrington Kyla , Miola José , Brunskill Nigel J , Brightling Christopher E , Barwell Julian , Wallace Susan E , Hsu Ron , Shepherd David J , Hollox Edward J , Wain Louise V , Tobin Martin D
Published: September 2018

EXCEED is a longitudinal population-based cohort which facilitates investigation of genetic, environmental and lifestyle-related determinants of a broad range of diseases and of multiple morbidity through data collected at baseline and via electronic healthcare record linkage. Recruitment has taken place in Leicester, Leicestershire and Rutland since 2013 and is ongoing, with 10 156 participants aged 30-69 to date. The population of Leicester is diverse and additional recruitment from the local South Asian community is ongoing. Participants have consented to follow-up for up to 25 years through electronic health records (EHR). Data available includes baseline demographics, anthropometry, spirometry, lifestyle factors (smoking and alcohol use) and longitudinal health information from primary care records, with additional linkage to other EHR datasets planned. Patients have consented to be contacted for recall-by-genotype and recall-by-phenotype sub-studies, providing an important resource for precision medicine research. We welcome requests for collaboration and data access by contacting the study management team via exceed@le.ac.uk.
Differential evolution and Markov chain Monte Carlo analyses of layer disorder in nanosheet ensembles using total scattering
Authors: Metz Peter C. , Koch Robert , Misture Scott T.
Published: September 2018

Assemblies of nanosheets are often characterized by extensive layer-position disorder. Coupled with the often minute coherent scattering domain size and relaxation of the nanosheet structure itself, unambiguous interpretation of X-ray and neutron scattering data from such materials is non-trivial. This work demonstrates a general approach towards refinement of layer-disorder information from atomic pair distribution function (PDF) data for materials that span the gap between turbostratism and ordered stacking arrangements. X-ray total scattering data typical of a modern rapid-acquisition PDF instrument are simulated for a hypothetical graphene-like structure using the program DIFFaX, from which atomic PDFs are extracted. Small 1 × 1 × 20 supercell models representing the stacking of discrete layer types are combined to model a continuous distribution of layer-position disorder. Models optimized using the differential evolution algorithm demonstrate improved fit quality over 75 Å when a single mean layer-type model is replaced with a constrained 31-layer-type model. Posterior distribution analyses using the Markov chain Monte Carlo algorithm demonstrate that the influence of layer disorder and finite particle size are correlated. However, the refined mean stacking vectors match well with the generative parameter set.
Low-cost disposable high-pressure setup for in situ X-ray experiments
Authors: Houlleberghs Maarten , Martens Johan A. , Breynaert Eric
Published: September 2018

A low-cost, flexible and fast method to create disposable sample cells suitable for in situ catalytic or material synthesis studies based on standard quartz capillaries, heat-shrinkable tubing and standard Swagelok components is described.