bluuebunny/crossref_metadata_2025 huggingface dataset:
Estonia’s Digital Transformation
Authors: Kattel Rainer , Mergel Ines
Published: October 2019

Estonia’s transition to free-market capitalism and liberal democracy is marked by three distinct features: economic success, digital transformation of its public sector, and a rapid increase and persistence of social inequality in Estonia. Indeed, Estonia has become one of the most unequal societies in Europe. Economic success and increasing social inequality can be explained as different sides of the same coin: a neoliberal policy mix opened markets and allowed globalization to play out its drama on a domestic stage, creating winners and losers. Yet Estonia has been highly successful in its digital agenda. Particularly interesting is how the country’s public sector led the digital transformation within this highly neoliberal policy landscape. While within economic policy, Estonia did indeed follow the famed invisible hand in rapidly liberalizing markets, in ICT, Estonia seems to have followed an entirely different principle of policymaking. In this domain, policy has followed the principle of the hiding hand, coined by Albert Hirschman: policy-makers sometimes take on tasks they think they can solve without realizing all the challenges and risks involved— and this may result in unexpected learning and creativity. The success of Estonia’s e-government has much to do with the principle of the hiding hand: naïvety and optimism propelled initial ‘crazy ideas’ in the early 1990s to become ingrained in ICT policy, enabling the creation of multiple highly cooperative and overlapping networks that span public–private boundaries.
Unleashing the Power of Mechanization
Authors: Diao Xinshen , Cossar Frances , Houssou Nazaire , Kolavalli Shashidhara
Published: October 2019

After reviewing recent developments in the uptake of agricultural mechanization in Ghana, and the factors that are driving the growth in farmers’ demand, this chapter discusses supply-side constraints to greater mechanization, and evaluates the government’s program of subsidized tractors through Agricultural Mechanization Services Centers (AMSECs). The chapter concludes that such interventions often lead to market distortions in machinery prices, encouraging rent-seeking behavior, and discouraging the development of private sector supply system. The program is also unnecessarily costly to the public sector. Instead, the government would be more effective in achieving its goals if it were to withdraw from the AMSEC program and instead play a more complementary and supporting role to the private sector. This might include funding appropriate mechanization research, technical training of young mechanics, and ensuring that financial institutions can provide the longer-term lending needed by private agents and farmers in the mechanization supply chain.
God and Gratuitous Evil
Authors: Hasker William
Published: October 2019

In Chapter 3 of this volume, Klaas Kraay presented a critique of William Hasker’s necessity-of-gratuitous-evil defense against the evidential problem of evil (the NGE defense). Hasker’s response here in Chapter 4 contends that the defense survives all of Kraay’s objections. Most important of these objections is the contention that there is far too much gratuitous evil to be accounted for by Hasker’s defense.
Unrestricted Actualization and Perfect Worlds
Authors: Almeida Michael
Published: October 2019

God unrestrictedly actualizes a state of affairs just in case God predicts that some state of affairs obtains. Unrestricted actualization ensures, inter alia, that, necessarily, God can actualize a morally perfect world—whether or not those worlds include libertarian free agents—and can actualize any possible future—whether or not that future is open. Chapter 11 addresses a series of thoughtful objections from Bruce Langtry on the possibility of unrestricted actualization (Chapter 10 in this volume).
Prediction and Providence
Authors: Langtry Bruce
Published: October 2019

Chapter 12 responds to Michael Almeida’s chapter in this volume, “Unrestricted Actualization and Perfect Worlds: A Reply to Langtry.” It concludes that Langtry’s main claims in his own chapter in this volume, “Unrestricted Actualization and Divine Providence” are undamaged by Almeida’s remarks.
“Not So Ridiculous”
Authors: Dadikhuda Davlat
Published: October 2019

This chapter explicates a distinctive argument that Avicenna offers for the existence of nature as a causal power in bodies. In doing that, the author shows the argument has two main targets: the Aristotelian tradition on the hand, who thought that the existence of nature, as an intrinsic principle of movement, was self-evident, and the Ash ͑arite occasionalist theological tradition on the other, who were anti-realists about all creaturely efficacious power, locating all efficacy instead in an extrinsic transcendent agent. The argument draws on two key premises: a regularity of events thesis and a version of the principle of sufficient reason (PSR). Based on these two premises, Avicenna offers a response to the issue in a way that attempts to preserve something from both traditions. For it allows, with the Ash ͑aris, the causal involvement of a transcendent being in the production of some effect or range of effects from some body; and yet still maintains, against them and with the Aristotelians, that the effect must occur in virtue of some property of that body, where the property in question makes a real causal contribution to the effect’s occurrence. This amounts to a properly Avicennian account.
Aquinas on the Sources of Wrongdoing
Authors: Williams Thomas
Published: October 2019

Colleen McCluskey begins Thomas Aquinas on Moral Wrongdoing with an overview of Aquinas’s account of human nature and his theory of human action. She discusses the powers of the soul, including the sensory appetite and its passions, the intellect, and the will. Crucially, she devotes considerable attention to the ways in which the passions can affect the intellect’s judgment and, thereby, the will. She then explores Aquinas’s account of the ontological status of evil as a privation, arguing that criticisms of the privation theory can be met, though the theory is not enough by itself to acquit God of responsibility for the existence of evil. The centerpiece of Thomas Aquinas on Wrongdoing is a careful exploration of Aquinas’s understanding of the three sources of moral wrongdoing: defects in the intellect (sins from ignorance), defects in the sensory appetite (sins from passion), and defects in the will (sins ex certa malitia, in which an agent chooses a lesser good, not in ignorance or under the influence of a passion, but knowingly). Finally, McCluskey examines vices, which are firmly rooted dispositions, acquired by repeated action, that prompt particular acts of wrongdoing. She provides a helpful overview of Aquinas’s treatment of the vices both in ST II-II, where the vices are discussed in relation to the virtues to which they are opposed, and in the contemporaneous De malo, questions 9–15, in which Gregory the Great’s list of seven capital vices provides the structuring principle.
Matching FinTech Advice to Participant Needs
Authors: Deschenes Stephen L. , Hammond P. Brett
Published: October 2019

The financial services industry is changing rapidly with the arrival of new economies of scale and networking effects attributable to FinTech, particularly via online or ‘robo’ advice. This chapter reviews the ‘robo-experience:’ how does it differ, if at all, from more traditional advice, and what is likely to happen next? After reviewing the goals and objectives of robo-advice, evolving advice models, who uses robo-advice, and investor behavior, we conclude that first adopters tend to be more affluent Millennial investors, as well as others seeking fast, mobile, and easy access to their finances. Nevertheless, though robo-advice has promised much, evidence is thin on the actual effects of using advice, such as changes in asset allocation and long-term effects on financial security.
1759 and 1794
Authors: Britton Jeanne M.
Published: October 2019

Adam Smith’s mid-eighteenth-century account of sympathy begins with an imagined scene of torture. After the excesses of the French Revolution, such speculative scenarios of political and juridical violence prompt more explicit articulations of sympathy. This chapter identifies an urgent clarification of sympathy’s abstract, imaginative, and potentially transgressive features in the post-Terror philosophical work of Smith’s French translator, Sophie de Grouchy, and William Godwin’s Caleb Williams. De Grouchy’s translation highlights the same aspects of Smith’s work—fraternity, abstraction, and physicality—that are fundamental features in novelistic revisions of sympathy. In its figures of the brother on the rack and a natural disaster in the Far East, Smith’s Theory initiates a transformation of visual perception into imaginative perspective that Godwin’s Caleb Williams explores in narrative form.
Letters in the Novel and the Novel in Letters
Authors: Britton Jeanne M.
Published: October 2019

This chapter argues that Henry Mackenzie’s novel in letters Julia de Roubigné marks a transition from epistolary novels that are characterized by numerous correspondents who betray a desperate need for response to nineteenth-century frame tales that unite multiple speakers and eager listeners. Predicting the continued force of epistolary affect and perspective in novels published well into the nineteenth century, Julia de Roubigné indicates the role that fictional scenes of sympathetic response play in the historical transition from the novel in letters to the letter in the novel. This function of sympathy points to the persistent significance of the emotional immediacy and multiple perspectives that are characteristic of a logic of epistolarity, which in turn guides the shifting speakers and listeners of retrospective frame tales, such as René, Frankenstein, and Wuthering Heights, discussed in later chapters.
Introduction
Authors: Britton Jeanne M.
Published: October 2019

Key figures in Smith’s definition of sympathy clarify the ways his definition is unique and representative in Enlightenment discourse and suggest significant correlations with narrative perspective. His figures of the brother on the rack and the impartial spectator make kinship, physical pain, visual perception, and abstract perspective central to his influential account of sympathy. In the effort to overcome human difference, his conception of perspective anticipates a novelistic version of sympathy that struggles to accommodate difference through shifting narrative perspectives. “Vicarious narratives” identifies intersections between second-hand emotions, or feeling another person’s emotions as if they were one’s own, and second-hand narratives, or telling another person’s story as if it were one’s own. Details of grammar and citation posit a grammar of vicarious experience that destabilizes the meaning of the first-person singular pronoun and challenges the association between the individual and the novel as a genre.
Justice and the Division of Labor
Authors: Altman Andrew
Published: October 2019

Teaching students to be complete citizens is a big job. However, it does not encompass everything. What do schools owe students? Plato’s Republic supposed we could learn about justice in an individual soul by looking at justice in the city—he called the latter “justice writ large.” Philosophers ever since have been skeptical, doubting that justice of the soul (doing justice to the parts of one’s soul) is akin to justice of the polis (members of a community doing justice to each other). My hypothesis here is that justice in our schools (a question of how to do justice to our students) is not like justice in the larger polis, either. Yet, our theorizing about justice has so far been largely concerned with justice writ large. Thus, when it comes to educational justice, much of our extant theorizing about justice may be no more than an analogy at best.
What’s So Good About Education?
Authors: Altman Andrew
Published: October 2019

Here we consider twin concerns. First, when a good is a purely positional good, and thus of no particular social value, markets are likely to oversupply it. Second, if education is instead a public good, and indeed a critically valuable public good, then markets are likely to undersupply it. To the extent that it is better to have educated neighbors, education is more or less a public good, and in particular, it is not a zero-sum game. It may be positional in a particular narrow context, but even there education is not, and cannot be, merely positional.
The Ineliminable Role of Markets in Schooling
Authors: Altman Andrew
Published: October 2019

This chapter identifies markets that currently frame the provision of schooling. Schools and school districts compete with one another for teachers in the labor market; people respond to labor market signals in deciding whether or not to train to become teachers; people exercise school choice through the housing market; and, as long as private schools are legal, those who can afford it can exit the public sector into private schools: in the UK, 7 percent of children attend private schools, and in the US about 12 percent do. The chapter argues that no market-free approach to education policy is available.
The Case Against Markets in Education
Authors: Altman Andrew
Published: October 2019

This chapter makes the case against markets in education. It identifies four issues often raised by opponents of markets. In a pure market system, private organizations would run schools, children would be allocated to schools through parental choice, there would be no government funding, and there would be no education-specific regulation of schools. The chapter gives reasons for believing that such a system would fall far short of the goals we should have for an education system. Then the chapter reviews the research on actual choice systems in the US, and argues that the evidence suggests that, whereas some charter and voucher schools may serve some students well, the preponderance of evidence does not support the claim that markets have made significant improvements in educational provision.
Tribology on the Small Scale
Authors: Mate C. Mathew , Carpick Robert W.
Published: October 2019

Friction, lubrication, adhesion, and wear are prevalent physical phenomena in everyday life and in many key technologies. The goal of this book is to incorporate a bottom up approach to friction, lubrication, and wear into a versatile textbook on tribology. This is done by focusing on how these tribological phenomena occur on the small scale—the atomic to the micrometer scale—a field often called nanotribology. The book covers the microscopic origins of the common tribological concepts: roughness, elasticity, plasticity, friction coefficients, and wear coefficients. Some macroscale concepts (like elasticity) scale down well to the micro- and atomic scale, while other macroscale concepts (like hydrodynamic lubrication) do not. In addition, this book also has chapters on topics not typically found in tribology texts: surface energy, surface forces, lubrication in confined spaces, and the atomistic origins of friction and wear. These chapters covered tribological concepts that become increasingly important at the small scale: capillary condensation, disjoining pressure, contact electrification, molecular slippage at interfaces, atomic scale stick-slip, and bond breaking. Numerous examples are provided throughout the book on how a nanoscale understanding of tribological phenomena is essential to the proper engineering of important new technologies such as MEMS, disk drives, and nanoimprinting. For the second edition, all the chapters have been revised and updated, with many new sections added to incorporate the most recent advancements in nanoscale tribology. Another important enhancement to the second edition is the addition of problem sets at the end of each chapter.
Surface Roughness
Authors: Mate C. Mathew , Carpick Robert W.
Published: October 2019

When two surfaces are brought into contact, they first touch where the summits of the surface asperities make contact. Consequently, surface roughness or topography strongly influences those physical phenomena associated with contact: friction, adhesion, and wear. This chapter discusses techniques for measuring the roughness of surfaces and the parameters frequently used to characterize this roughness. As atomic force microscopy (AFM) and optical interferometry are currently the predominant tools for characterizing roughness, these techniques are discussed at some length. Examples are given for determining not only the standard roughness parameters (the standard deviation of surface heights, the mean radius of curvature of asperity summits, waviness, and the average and rms of surface heights), but also for determining the surface roughness power spectrum, which has gained importance in recent tribology theories. The topography of self-affine fractal surfaces is also discussed along with the tribological importance of these surfaces.
Friction
Authors: Mate C. Mathew , Carpick Robert W.
Published: October 2019

This chapter introduces friction as it manifests itself in everyday life. The chapter begins with Amontons’ law (1699) that friction is proportional to the loading force between contacting surfaces (the proportionality constant is called the coefficient of friction). The two primary mechanisms for unlubricated friction are adhesive friction and plowing friction, with the predominant mechanism generally being adhesive friction. Adhesive friction is proportional to the real area of contact; for rough surfaces, this contact area is proportional to the loading force, providing a physical underpinning for Amontons’ law. Processes like the nanoscale flow of atoms and molecules around contact points results in the force needed to induce sliding (static friction) being higher than the force needed to maintain sliding (kinetic friction). Friction decreasing with increasing velocity leads stick-slip motion of the sliding surfaces, where the slip distance can be as short as the distance between atoms.
Physical Origins of Surface Forces
Authors: Mate C. Mathew , Carpick Robert W.
Published: October 2019

The energies and forces between contacting surfaces originate from the interaction forces between atoms and molecules. This chapter discusses how these atomic level forces lead to various types of force–separation relations as two surfaces are brought into contact. This chapter covers the interactions between atoms (repulsive atomic potentials and van der Waals interactions), the interactions within liquid and aqueous media (solvation forces, electrostatic double layer, hydration repulsion, hydrophobic attraction), and electrostatic interactions from contact electrification. Due to their ubiquitous effect on adhesion, van der Waals interactions are discussed at length, including examples for calculating adhesive forces in different geometries using Hamaker constants.
Lubrication
Authors: Mate C. Mathew , Carpick Robert W.
Published: October 2019

For situations where high friction is not explicitly needed, lubricants are used to reduce friction and wear to acceptable levels. Lubricants function mainly by introducing a layer of solid or liquid material with low shear strength between two sliding surfaces. This chapter covers the basic regimes of lubrication: hydrostatic, hydrodynamic, elastohydrodynamic, mixed, and boundary. Viscosity is the most important physical parameter describing a lubricant, and it is thoroughly discussed in this chapter. Slippage of lubricants and other liquids against solid surfaces is also discussed. The chapter also discusses the basic mechanisms and types of bearings that provide hydrodynamic and elastohydrodynamic lubrication.
Lubrication in Tight Spots
Authors: Mate C. Mathew , Carpick Robert W.
Published: October 2019

This chapter discusses the interesting phenomena that happen when the thickness of a lubricant film is reduced to nanoscale dimensions. For liquid lubricants sandwiched between two solid surfaces, the interesting phenomena associated with confined liquids include: molecules forming a layered structure, enhanced viscosity, and solidification. In boundary lubrication, an adsorbed monolayer resists penetration of contacting asperities and sliding takes place over the low shear strength surface of the boundary lubricant. The absence of boundary lubrication can lead to cold welding where adhesion at the interface leads to ultra-high friction and seizure. The last part of this chapter discusses how capillary and disjoining pressures lead to the formation of lubricant menisci around contacting asperities from a thin lubricant film on one of the surfaces and how these menisci influence adhesion and friction. The kinetics of meniscus formation from capillary condensation and its impact on friction are also discussed.
Bayesian Philosophy of Science
Authors: Sprenger Jan , Hartmann Stephan
Published: October 2019

“Bayesian Philosophy of Science” addresses classical topics in philosophy of science, using a single key concept—degrees of beliefs—in order to explain and to elucidate manifold aspects of scientific reasoning. The basic idea is that the value of convincing evidence, good explanations, intertheoretic reduction, and so on, can all be captured by the effect it has on our degrees of belief. This idea is elaborated as a cycle of variations about the theme of representing rational degrees of belief by means of subjective probabilities, and changing them by a particular rule (Bayesian Conditionalization). Partly, the book is committed to the Carnapian tradition of explicating essential concepts in scientific reasoning using Bayesian models (e.g., degree of confirmation, causal strength, explanatory power). Partly, it develops new solutions to old problems such as learning conditional evidence and updating on old evidence, and it models important argument schemes in science such as the No Alternatives Argument, the No Miracles Argument or Inference to the Best Explanation. Finally, it is explained how Bayesian inference in scientific applications—above all, statistics—can be squared with the demands of practitioners and how a subjective school of inference can make claims to scientific objectivity. The book integrates conceptual analysis, formal models, simulations, case studies and empirical findings in an attempt to lead the way for 21th century philosophy of science.
Learning Conditional Evidence
Authors: Sprenger Jan , Hartmann Stephan
Published: October 2019

Learning indicative conditionals and learning relative frequencies have one thing in common: they are examples of conditional evidence, that is, evidence that includes a suppositional element. Standard Bayesian theory does not describe how such evidence affects rational degrees of belief, and natural solutions run into major problems. We propose that conditional evidence is best modeled by a combination of two strategies: First, by generalizing Bayesian Conditionalization to minimizing an appropriate divergence between prior and posterior probability distribution. Second, by representing the relevant causal relations and the implied conditional independence relations in a Bayesian network that constrains both prior and posterior. We show that this approach solves several well-known puzzles about learning conditional evidence (e.g., the notorious Judy Benjamin problem) and that learning an indicative conditional can often be described adequately by conditionalizing on the associated material conditional.
Simplicity and Model Selection
Authors: Sprenger Jan , Hartmann Stephan
Published: October 2019

Is simplicity a virtue of a good scientific theory, and are simpler theories more likely to be true or predictively successful? If so, how much should simplicity count vis-à-vis predictive accuracy? We address this question using Bayesian inference, focusing on the context of statistical model selection and an interpretation of simplicity via the degree of freedoms of a model. We rebut claims to prove the epistemic value of simplicity by means of showing its particular role in Bayesian model selection strategies (e.g., the BIC or the MML). Instead, we show that Bayesian inference in the context of model selection is usually done in a philosophically eclectic, instrumental fashion that is more tuned to practical applications than to philosophical foundations. Thus, these techniques cannot justify a particular “appropriate weight of simplicity in model selection”.
Les normes de l’évaluation diagnostique du trouble du spectre de l’autisme
Authors: Brian Jessica A , Zwaigenbaum Lonnie , Ip Angie
Published: October 2019

En raison de la prévalence croissante du trouble du spectre de l’autisme (TSA), il est devenu nécessaire d’accroître la capacité diagnostique des pédiatres communautaires et des autres dispensateurs de soins de première ligne à l’égard de cette affection. Même si les données probantes indiquent que certains enfants peuvent obtenir un diagnostic définitif avant l’âge de deux ans, nombreux sont ceux qui ne sont pas diagnostiqués avant l’âge de quatre ou cinq ans. La plupart des directives cliniques recommandent de faire participer une équipe multidisciplinaire au processus diagnostique de TSA. Même si trois directives récentes sur le TSA recommandent une période d’attente maximale de trois à six mois, dans bien des lieux au Canada, il faut souvent attendre plus d’un an entre la demande de consultation et la tenue de l’évaluation diagnostique du TSA par une équipe. Il faudrait former plus de dispensateurs de soins pédiatriques pour diagnostiquer les cas de TSA moins complexes. Le présent document de principes fournit aux cliniciens pédiatriques communautaires des recommandations, des outils et des ressources pour effectuer l’évaluation diagnostique du TSA ou y contribuer. Il contient également des conseils sur les consultations en vue d’une évaluation complète des besoins pour la planification des traitements et des interventions, selon une approche flexible et multiniveau.
Post-diagnostic management and follow-up care for autism spectrum disorder
Authors: Ip Angie , Zwaigenbaum Lonnie , Brian Jessica A
Published: October 2019

Paediatricians and other primary care providers are well positioned to provide or coordinate ongoing medical and psychosocial care and support services for children with autism spectrum disorder (ASD). This statement provides recommendations and information on a range of interventions and resources, to help paediatric care providers optimize care for children with ASD and support their families. The management of ASD includes treating medical and psychiatric co-morbidities, behavioural and developmental interventions, and providing supportive social care services to enhance quality of life for affected children and families.
s-wave quasiparticle resonance in neutron-rich drip-line nuclei
Authors: Kobayashi Yoshihiko , Matsuo Masayuki
Published: October 2019

We investigate unbound single-particle states in pair-correlated drip-line nuclei by describing a low-energy elastic scattering of a neutron in the $s$-wave within the framework of the coordinate space Hartree–Fock–Bogoliubov (Bogoliubov–de Genne) equation. A numerical study is performed for a neutron drip-line carbon isotope where the neutron $2s_{1/2}$ orbit is located close to zero energy. Analyzing the S-matrix poles of the elastic scattering, we discuss properties of the $s$-wave quasiparticle resonance and, in particular, behaviors characteristic to drip-line nuclei. It is found that the S-matrix has two pairs of poles; one pair appears as either a weakly bound state, a virtual state or a resonance while the other pair makes a contribution analogous to a bound single-particle state. The $s$-wave quasiparticle resonance emerges with a large variation depending on the pairing gap and the single-particle energy of the $s$-orbit.
EXPOSURE INHOMOGENEITY FROM 241AM AND 90SR/90Y SOURCES IN TERMS OF THE EYE LENS MONITORING IN THE NUCLEAR FACILITIES
Authors: Yoshitomi H , Kowatari M
Published: October 2019

This article highlights the issues of exposure inhomogeneity that are relative to eye lens monitoring for low-energy photons from 241Am and beta-rays from 90Sr/90Y including a personal protective equipment because eye lens exposure has been concerned more than before due to the proposed reduction of relevant dose limit. These nuclides are common and concerned sources in the nuclear industry. Our previous study presented a quantitative estimation of exposure inhomogeneity, which was applied to simple but typical exposure situations. For the present study, exposure inhomogeneity of 241Am was approximately within a factor of 1.6, implying a more homogeneous situation than expected. Regarding 90Sr/90Y exposure, estimation from both Hp(10) and Hp(0.07) on trunk would lead to an over- or underestimation by a factor of more than 10. In contrast, Hp(3) measurement on trunk will improve by up to a factor of 2. With respect to the personal protective equipment, lead apron and protective glasses are effective for the 60-keV photons for both anterior-posterior and rotational irradiations, while a full-face respirator can reduce the eye lens dose by approximately 17% for 90Sr/90Y betas. As a whole, this study demonstrated that the effect of protective equipment could be effectively incorporated into the homogeneity evaluation.
Achromobacter xylosoxidans in hospital environments: still waters run deep!
Authors: Marion-Sanchez Karine , Olive Claude , Platon Marie-Georges , Cesarine Myriam , Derancourt Christian , Pailla Karine
Published: October 2019

Background

Hospital reservoirs of Achromobacter xylosoxidans, responsible for nosocomial infections, are poorly known.

Methods

We examined the growth, survival and biofilm formation of five A. xylosoxidans strains for up to 2 y in distilled, dialysis or microfiltered water. Each strain was inoculated at 102 CFU/ml without adding nutrients.

Results

All strains grew at a level of 3x103 to 1.5x107 CFU/ml; each strain showed a preferred water type. Strains isolated from quaternary ammoniums showed the highest ability to grow and form biofilms in nutrient-poor waters.

Conclusion

Medical waters and notably sterile distilled water bottles appear to be long-lasting reservoirs of A. xylosoxidans.
Revision of Oligocene ‘Paraphiomys’ and an origin for crown Thryonomyoidea (Rodentia: Hystricognathi: Phiomorpha) near the Oligocene–Miocene boundary in Africa
Authors: Sallam Hesham M , Seiffert Erik R
Published: October 2019

‘Paraphiomys’ simonsi is a phiomorph rodent from the early Oligocene of Egypt (~29–30 Mya) that has historically been aligned with much younger (< ~20 Mya) Miocene species of the genera Paraphiomys and Neosciuromys. Here, we use Bayesian tip-dating analysis of a 109-character morphological matrix containing 57 living and extinct ctenohystricans to test these proposed placements for ‘Paraphiomys’ simonsi. Our analyses provide support for the exclusion of ‘Paraphiomys’ simonsi from both Paraphiomys and Neosciuromys and justify the establishment of a new genus (Monamys gen. nov.) for this stem thryonomyoid. These analyses also indicate that the divergence of the extant dassie rat Petromus from the extant cane rat Thryonomys (i.e. origin of crown Thryonomyoidea) occurred ~23.7 Mya, close to the Oligocene–Miocene boundary and in close agreement with recent molecular estimates for this split. Miocene Neosciuromys, Paraulacodus, Protohummus and the type species of Paraphiomys are identified as stem thryonomyids, whereas the Namibian species Apodecter stromeri, Tufamys woodi, ‘Paraphiomys’ australis and ‘Paraphiomys’ roessneri are identified for the first time as stem petromurids, raising the possibility of a long period of endemic petromurid evolution in south-west Africa. Comparison of molecular divergence estimates with our optimal tip-dated topology suggests that stem bathyergoids are most likely to have arisen from late Eocene and early Oligocene ‘phiomyids’.
Carbon monoxide ameliorates acetaminophen‐induced liver injury by increasing hepatic HO‐1 and Parkin expression
Authors: Chen Yingqing , Park Hyeok‐Jun , Park Jeongmin , Song Hyun‐Chul , Ryter Stefan W. , Surh Young‐Joon , Kim Uh‐Hyun , Joe Yeonsoo , Chung Hun Taeg
Published: October 2019

Acetaminophen (APAP) is widely used as an antifebrile and analgesic drug at recommended doses, whereas an overdose of APAP can cause severe liver damage. The molecular mechanisms underlying APAP‐induced liver damage remain incompletely understood. Carbon monoxide (CO), an end‐product of heme oxygenase (HO)‐1 activity, can confer anti‐inflammatory and antiapoptotic properties in cellular models of toxicity via regulation of mitochondrial function. The objective of this study was to evaluate the effects of CO on APAP‐induced hepatotoxicity and CO's relationship to regulation of endoplasmic reticulum (ER) stress and mitochondrial signaling using CO‐releasing molecules or low concentrations of CO applied as pretreatment or post‐treatment. Using genetic deletion or knockdown approaches in alpha mouse liver cells or primary hepatocytes, respectively, we investigated the role of HO‐1 and the mitophagy regulator protein Parkin on APAP‐induced expression of the ER stress‐associated apoptosis regulator cytosine‐cytosine‐adenosine‐adenosine‐thymidine (CCAAT)/enhancer‐binding protein homologous protein (CHOP). We found that CO induced Parkin expression in hepatocytes via the protein kinase RNA‐like ER kinase/eukaryotic translation initiation factor 2‐α/activating transcription factor‐4 signaling pathway. Additionally, CO gas inhalation significantly alleviated APAP‐induced liver damage in vivo and correspondingly reduced serum alanine aminotransferase and aspartate aminotransferase levels as well as proinflammatory cytokines and reduced the expression of CHOP in liver tissues while dramatically increasing hepatic HO‐1 and Parkin expression. We found that the protective effects of CO on APAP‐induced liver damage were mediated by down‐regulation of CHOP at a transcriptional and post‐translational level via induction of HO‐1 and Parkin, respectively, and associated with decreases in reactive oxygen species production and JNK phosphorylation. We conclude that CO may represent a promising therapeutic agent for APAP‐induced liver injury.—Chen, Y., Park, H.‐J., Park, J., Song, H.‐C., Ryter, S. W., Surh, Y.‐J., Kim, U.‐H., Joe, Y., Chung, H. T. Carbon monoxide ameliorates acetaminophen‐induced liver injury by increasing hepatic HO‐1 and Parkin expression. FASEB J. 33, 13905‐13919 (2019). www.fasebj.org
Risk factors for the first episode of Acinetobacter baumannii resistant to colistin infection and outcome in critically ill patients
Authors: Mantzarlis Konstantinos , Makris Demosthenes , Zakynthinos Epaminondas
Published: October 2019

Introduction. To identify risk factors for the first episode of

Acinetobacter baumannii

resistant to colistin (ABCR) infection in critically ill patients.

Aim. Prospective observational study.

Methodology. ICU patients who required mechanical ventilation for >48 h during a 36 month period. Clinical and microbiological data were studied; characteristics of patients infected with ABCR were compared with those of critically ill patients who presented infection due to

A. baumannii

sensitive to colistin (ABCS).

Results. Twenty patients presented with ABCR infection, and 57 patients ABCS infection. Compared to patients with ABCS infection, patients suffering from ABCR infection had received more frequent and/or for longer duration dosing of several antibiotics active against Gram-negative bacteria (P<.05). Moreover, the duration of mechanical ventilation, and the presence of invasive procedures and tracheostomy prior to infection were associated with ABCR infections. The duration of carbapenem administration was an independent risk factor for ABCR infection [odds ratio (OR), 1.21; 95 % confidence interval (95 %, CI), 1.00 to 1.45; P=.049]. Mortality rate for patients with ABCR infection was higher (85 vs 39 % for the ABCS group). Sequential organ failure assessment score on admission, Charlson score and ABCR infection were independent risk factors for mortality.

Conclusion. ABCR infection is a life-threatening infection, which might be more common in patients with previous use of antibiotics, especially carbapenems.
Three-dimensional Structural Interrelations between Cells, Extracellular Matrix and Mineral in Vertebrate Mineralization
Authors: Zou Zhaoyong , Tang Tengteng , Macías-Sánchez Elena , Sviben Sanja , Landis William J. , Bertinetti Luca , Fratzl Peter
Published: October 2019

The spatial-temporal relationship between cells, extracellular matrices and mineral deposits is fundamental for an improved understanding mineralization mechanisms in vertebrate tissues. By utilizing focused ion beam-scanning electron microscopy with serial surface imaging, normally mineralizing avian tendons have been studied with nanometer resolution in three dimensions with volumes exceeding tens of microns in range. These parameters are necessary to yield fine ultrastructural details while encompassing tissue domains sufficient to provide a comprehensive overview of the interrelationships between the tissue structural constituents. Investigation reveals a novel complex cellular network in highly mineralized tendon aspects, where ∼100 nm diameter canaliculi emanating from cell (tenocyte) lacunae surround extracellular collagen fibril bundles. Canaliculi are linked to smaller channels of ∼40 nm diameter, occupying spaces between fibrils. Close to the tendon mineralization front, calcium-rich globules appear between the fibrils and, with time, mineral propagates along and within collagen. These close associations between tenocytes, canaliculi, small channels, collagen and mineral suggest a new concept for the mineralization process, where ions and/or mineral precursors may be transported through spaces between fibrils before they crystallize along the surface of and within the fibrils.

Significance Statement

The basic mechanism by which vertebrate collagenous tissues are mineralized is still not fully elucidated, despite the importance of this process for skeletal formation and regeneration. Through three-dimensional imaging of the cellular network together with the extracellular matrix and mineral deposits, the present work investigates normally mineralizing avian leg tendon as a model system for vertebrates in general. The data support a mechanism where mineral ions and possible mineral precursors are initially present in interfibrillar collagen spaces and are subsequently translocated to neighboring collagen fibrils. Mineral particles then nucleate in association with collagen to form the well known collagen-mineral composite material of the skeleton.
Positioning Personal Polygenic Risk score against the population background
Authors: Leonenko Ganna , Baker Emily , Schmidt Karl Michael , Escott-Price Valentina ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

The polygenic risk scores (PRS) approach has been widely used across different traits for estimating polygenic risk, pleiotropy and disease prediction, but mostly in European populations. The predictive ability of the PRS in non-European populations is currently limited due to the lack of genetic research performed in populations of non-European ancestry. One of the main challenges of the practical use of PRS is to place an individual’s personal score in the context of the PRS distribution in the underlying population. In this paper we present an approach for estimating the parameters of the PRS distribution in a population using summary information from public data.

Unstandardized PRS are usually not directly comparable even between European studies. Our approach can be used for standardisation whilst accounting for genotyping platforms, data quality and ancestry. It can be applied to assessing polygenic disease risk for individuals from a European population for any complex genetic disorder and, assuming that most of the disease risk loci are likely to be shared between populations, to estimating the disease risk for individuals from other populations. We demonstrate the precision of our method with simulations. We show the utility of our estimates in application to Alzheimer’s disease in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. We present population specific PRSs for different populations using 1000 Genomes data.
Test-time augmentation for deep learning-based cell segmentation on microscopy images
Authors: Moshkov Nikita , Mathe Botond , Kertesz-Farkas Attila , Hollandi Reka , Horvath Peter
Published: October 2019

Recent advancements in deep learning have revolutionized the way microscopy images of cells are processed. Deep learning network architectures have a large number of parameters, thus, in order to reach high accuracy, they require massive amount of annotated data. A common way of improving accuracy builds on the artificial increase of the training set by using different augmentation techniques. A less common way relies on test-time augmentation (TTA) which yields transformed versions of the image for prediction and the results are merged. In this paper we describe incorporating the test-time argumentation prediction method into two major segmentation approaches used in the single-cell analysis of microscopy images, namely semantic segmentation using U-Net and instance segmentation using Mask R-CNN models. Our findings show that even using only simple test-time augmentations, such as rotation or flipping and proper merging methods, will result in significant improvement of prediction accuracy. We utilized images of tissue and cell cultures from the Data Science Bowl (DSB) 2018 nuclei segmentation competition and other sources. Additionally, boosting the highest-scoring method of the DSB with TTA, we could further improve and our method has reached an ever-best score at the DSB.
Improving cell distribution on 3D additive manufactured scaffolds through engineered seeding media density and viscosity
Authors: Cámara-Torres M. , Sinha R. , Mota C. , Moroni L.
Published: October 2019

In order to ensure the long-termin vitroandin vivofunctionality of cell-seeded 3D scaffolds, an effective and reliable method to control cell seeding efficiency and distribution is crucial. Static seeding on 3D additive manufactured scaffolds made of synthetic polymers still remains challenging, as it often results in poor cell attachment, high cell sedimentation and non-uniform cell distribution, due to gravity and to the intrinsic macroporosity and surface chemical properties of the scaffolds. In this study, the bio-inert macromolecules dextran and Ficoll were used for the first time as temporary supplements to alter the viscosity and density of the seeding media, respectively, and improve the static seeding output. The addition of these macromolecules drastically reduced the cell sedimentation velocities, allowing for homogeneous cell attachment to the scaffold filaments. Both dextran- and Ficoll-based seeding methods supported human mesenchymal stromal cells viability and osteogenic differentiation post-seeding. Interestingly, the improved cell distribution led to increased matrix production and mineralization compared to scaffolds seeded by conventional static method. These results suggest a simple and universal method for an efficient seeding of 3D additive manufactured scaffolds, independent of their material and geometrical properties, and applicable for bone and various other tissue regeneration.
What would it take to describe the global diversity of parasites?
Authors: Carlson Colin J. , Dallas Tad A. , Alexander Laura W. , Phelan Alexandra L. , Phillips Anna J.
Published: October 2019

How many parasites are there on Earth? Here, we use helminth parasites to high-light how little is known about parasite diversity, and how insufficient our current approach will be to describe the full scope of life on Earth. Using the largest database of host-parasite associations and one of the world’s largest parasite collections, we estimate a global total of roughly 100,000 to 350,000 species of helminth endoparasites of vertebrates, of which 85% to 95% are unknown to science. The parasites of amphibians and reptiles remain the most poorly described, but the majority of undescribed species are likely parasites of birds and bony fish. Missing species are disproportionately likely to be smaller parasites of smaller hosts in undersampled countries. At current rates, it would take centuries to comprehensively sample, collect, and name vertebrate helminths. While some have suggested that macroecology can work around existing data limitations, we argue that patterns described from a small, biased sample of diversity aren’t necessarily reliable, especially as host-parasite networks are increasingly altered by global change. In the spirit of moon-shots like the Human Genome Project and the Global Virome Project, we consider the idea of a Global Parasite Project: a global effort to transform parasitology and inventory parasite diversity at an unprecedented pace.
Single-cell sequencing of mouse thymocytes reveals mutational landscape shaped by replication errors, mismatch repair and H3K36me3
Authors: Aska Elli-Mari , Dermadi Bebek Denis , Kauppi Liisa
Published: October 2019

Background

DNA mismatch repair (MMR) safeguards genome stability by correcting errors made during DNA replication.In vitroevidence indicates that the MMR machinery is recruited to chromatin via H3K36me3, a histone mark enriched in 3’ exons of genes and associated with transcriptional activity. To dissect how replication errors, abundance of H3K36me3 and MMR together shape the mutational landscape in normal mammalian cells, we applied single-cell exome sequencing to thymic T cells isolated from MMR-proficient (Mlh1+/+) and MMR-deficient (Mlh1−/−) mice.

Results

Using single-cell exome sequencing we identified short deletions as sensitive and quantifiable reporters of MMR-dependent mutations. We found H3K36me3-enrichedHuwe1andMcm7genes to be mutational hotspots exclusive toMlh1−/−T cells. InMlh1+/+cells, exons of H3K36me3-enriched genes had a lower mutation frequency compared to H3K36me3-depleted genes. Moreover, within transcriptionally active genes, 3’ exons, often H3K36me3-enriched, rather than 5’ exons had significantly fewer MMR-dependent mutations, indicating that MMR operates more efficiently within 3’ exons inMlh1+/+T cells.

Conclusions

Our results provide evidence that H3K36me3 confers preferential MMR-mediated protection from transcription-associated deleterious replication errors. This offers an attractive concept of thrifty MMR targeting, where genes critical for the development of given cell type are preferentially shielded fromde novomutations by H3K36me3-guided MMR.