bluuebunny/crossref_metadata_2025 huggingface dataset:
The Formula of Concord and Lutheran Christology in the 1570s
Authors: Cross Richard
Published: November 2019

This chapter gives an account of the debates between the followers of Melachthon and the followers of Brenz in the years immediately prior to the Formula of Concord (1577). It then describes the formula itself, and finally the later Christology of Martin Chemnitz, which differs sharply from his earlier views in a number of key respects. It shows that the two parts of the formula, composed respectively by Andreae and Chemnitz, while agreeing that Christ’s human nature possesses divine attributes, diverge in numerous ways on questions of both Christological metaphysics and Christological semantics, and that these divergences render the two parts prima facie incompatible.
Chi-Squared Data Analysis and Model Testing for Beginners
Authors: Witkov Carey , Zengel Keith
Published: November 2019

This book is the first to make chi-squared model testing, one of the data analysis methods used to discover the Higgs boson and gravitational waves, accessible to undergraduate students in introductory physics laboratory courses. By including uncertainties in the curve fitting, chi-squared data analysis improves on the centuries old ordinary least squares and linear regression methods and combines best fit parameter estimation and model testing in one method. A toolkit of essential statistical and experimental concepts is developed from the ground up with novel features to interest even those familiar with the material. The presentation of one- and two-parameter chi-squared model testing, requiring only elementary probability and algebra, is followed by case studies that apply the methods to simple introductory physics lab experiments. More challenging topics, requiring calculus, are addressed in an advanced topics chapter. This self-contained and student-friendly introduction to chi-squared analysis and model testing includes a glossary, end-of-chapter problems with complete solutions, and software scripts written in several popular programming languages, that the reader can use for chi-squared model testing. In addition to introductory physics lab students, this accessible introduction to chi-squared analysis and model testing will be of interest to all who need to learn chi-squared model testing, e.g. beginning researchers in astrophysics and particle physics, beginners in data science, and lab students in other experimental sciences.
Two–Parameter Chi-squared Analysis
Authors: Witkov Carey , Zengel Keith
Published: November 2019

The chi-squared parameter estimation and model testing methodology is extended to the two-parameter case of a line with a slope and an intercept. Chi-squared is shown to be a paraboloid and is displayed in a contour plot. Techniques for extracting parameter correlations and uncertainties are developed. End-of-chapter problems are included (with solutions in an appendix).
Advanced Topics
Authors: Witkov Carey , Zengel Keith
Published: November 2019

A variety of advanced topics are introduced to offer greater challenge for beginners and to answer thorny questions often asked by early researchers who are just starting to use chi-squared analysis. Topics covered include probability density functions, p-values, the derivation of the chi-squared probability density function and its uses, reduced chi-squared, the Poisson distribution, and advanced techniques for maximum likelihood estimation in cases where uncertainties are not Gaussian or the model is nonlinear. Problems are included (with solutions in an appendix).
A Sordid, Futureless Mess?
Authors: Marsh John
Published: November 2019

The first part of the chapter surveys how love fared in the film and literary fiction of the period, including the scandalous pre-Code film Baby Face, John O’Hara’s BUtterfield 8, and Mary McCarthy’s The Company She Keeps. In those works, love is a lost cause, mired in a cauldron of selfishness, venereal disease, and general tawdriness that reflected the hard times love had fallen on during the decade. After this survey of 1930s sordidness and lovelessness, the chapter offers a theory as to why so many writers and, for a time, the culture at large may have suddenly lost faith in love. (In short, the economy did it.) Its final take on the decade is that heterosexual love, like the economy with which its fate so closely intertwined, eventually recovered from the Depression that it, too, had been thrown into.
Scales—Idealism or Compromise?
Authors: Townsend Peter
Published: November 2019

While most people initially think musical scales are fixed and can be defined by a piano keyboard, this is far from the truth. In reality there are perhaps 80 scales in use around the world. In principle, piano tuning uses the idealized mathematical model of equal temperament tuning. However, this produces dissonances when many note chords are being played, and so active ‘mistuning’ flattens lower notes and sharpens the high ones. Scales are contrasted, and even the idea of a ‘perfect’ frequency ratio for different notes, as proposed by Pythagoras, is challenged. This realization can explain why people sing or play notes in scales which do not fit an inflexible keyboard.
Definitions and Parameters
Authors: Siwicki Christopher
Published: November 2019

This chapter explores the idea of architectural restoration in the Roman world—how ancient authors wrote about it as a subject. It also includes a review of existing scholarship on the subject, defines the concept of built heritage and its applicability to the study of antiquity, and explains the chronological and geographical parameters of the investigation. The final part of the chapter presents a survey of developments in Roman architecture as well as the transformation that the city of Rome underwent between the Great Fire of ad 64 and the early ad 120s, thereby establishing the context in which many of the subsequent discussions can be understood.
1914–18—Keeping the Spiritual Home Fires Burning
Authors: Field Clive D.
Published: November 2019

The First World War has traditionally been thought to have had a catastrophic and long-standing impact on organized religion in Britain, but this bleak picture has been qualified in recent historiography. By seriously disrupting the Churches’ work and Sunday observance, and broadening the range and affordability of secular leisure opportunities, the war proved an ‘accelerant’ rather than a novel agent of secularization. Religious allegiance held fairly steady, although the Free Churches continued to lose ground, there was (speculatively) some increase in religious ‘nones’, and growth in Spiritualism. One million Sunday scholars were permanently lost during the war, partly as a consequence of the falling birth rate. In Protestant Churches, there was a short-lived surge in attendance at the start of the war, fuelling hopes of religious revival, but it quickly gave way to ongoing decline, which was not reversed after the conflict. There were modest rises in Catholic and Jewish populations.
Introduction. An American Project
Authors: Amorosa Paolo
Published: November 2019

The introduction sets the historiographical and political stakes of narrating and analyzing Scott’s campaign for the Spanish origin of international law, drawing on current methodological discussions and the role of the concept of equality in our political discourse. It also explains the relation of the book with previous scholarship on Scott and literature on the rise of international legal networks in the Americas in the early twentieth century. Moreover, it elaborates on the reasons for the primarily descriptive style the text adopts and on certain related choices of language. The introduction ends with an outline of the structure of the book and of the individual chapters.
Historical perspective and initial conditions
Authors: Nayyar Deepak
Published: November 2019

This chapter provides a historical perspective on Asia in the world economy with a focus on the colonial era, and sketches a profile of the prevalent initial conditions when Asian countries became independent. Two centuries ago, Asia accounted for two-thirds of world population and almost three-fifths of world income. Its decline and fall during the colonial era, associated with deindustrialization, was attributable to its integration with the world economy, through trade and investment, driven by imperialism. Fifty years ago, then, Asia was the poorest continent in the world. Its even worse demographic and social indicators of development epitomized its underdevelopment. Such initial conditions were the starting point in its journey to development. But most Asian countries did have a long history of well-structured states, and cultures, which were not entirely destroyed by colonialism. Their different pasts, embedded in histories albeit shaped by colonial legacies, also influenced future outcomes in development.
Macroeconomics of growth
Authors: Nayyar Deepak
Published: November 2019

Economic growth over fifty years in the Asian-14 has been stunning. Investment and savings, which rose rapidly, were the main drivers of growth. Education was also a sustained driver of growth on the supply-side. From the demand-side, growth was primarily private-consumption-expenditure led and investment led. The interaction between the supply-side and the demand-side suggests a virtuous circle of cumulative causation, where rapid investment growth coincided in time with rapid export growth, leading to rapid GDP growth. In macroeconomic management, the successful countries did not follow orthodox prescriptions of balanced budgets and price stability. Their primary macroeconomic objectives were economic growth and employment creation. Their macroeconomic policies were also more versatile in their use of policy instruments. Their success in maintaining high growth rates increased their degrees of freedom, which enabled them to finance government deficits and raise sustainable levels of government borrowing, while making higher inflation rates politically more acceptable, which would not have been possible if economic growth was slow.
Structural change and economic transformation
Authors: Nayyar Deepak
Published: November 2019

Development in Asia has been associated with a structural transformation of economies. In this process, economic growth drove structural change from the demand-side as incomes rose and production activities followed, while structural change drove economic growth from the supply-side as labour moved from low-productivity to higher-productivity activities. Such labour transfer between sectors was growth-promoting in earlier stages, while productivity increase within sectors was growth-promoting in later stages. There was an exit of labour from agriculture everywhere, while the services sector progressively became the largest employer, with the highest output-share, across Asia. The process of structural transformation remains incomplete. In many countries it is necessary to address the neglect of agriculture and renew the emphasis on manufacturing, just as it is essential to exploit the synergies between manufacturing and services. Economic growth cannot be sustained and structural transformation cannot be completed even if one of three sectors is a weak link in the chain.
Openness and industrialization
Authors: Nayyar Deepak
Published: November 2019

The past fifty years witnessed a marked increase in the degree of economic openness in Asia, reflected in its rising share of world trade and investment flows. There were, of course, differences between countries, depending upon their size. The pace of industrialization was also impressive. For Asia, and the Asian-14, the share of manufacturing in GDP rose from one-tenth in 1970 to one-fourth in 2016. But industrialization was most unequal even among the Asian-14. Economic openness has performed a critical supportive role in the process, wherever it has been in the form of strategic integration with, rather than passive insertion into, the world economy. Analysis of the industrialization experience in the Asian-14 shows that openness, while necessary, was not sufficient. It was conducive to industrialization only when combined with sensible industrial policy that was implemented by effective governments. In future, however, technological learning and technological capabilities are also essential to provide the foundations for sustaining industrialization.
Markets, governments, and politics
Authors: Nayyar Deepak
Published: November 2019

This chapter shows that governments performed a critical role, ranging from leader to catalyst or supporter, in the economic transformation of Asia spanning half a century, while their willingness and ability to do so depended on the nature of the state, which in turn was shaped by politics. It argues that the state and the market are complements rather than substitutes and that the two institutions must adapt to each other in an interactive co-operative manner over time. Success at development in Asia was about managing this evolving relationship between states and markets, by finding the right balance in their respective roles, which also changed over time. This experience suggests that efficient markets and effective governments, in tandem, provided the way forward to development. It is only institutionalized checks and balances that can make governments more development-oriented and people-friendly. Thus, for Asia’s continuing journey in development, democracy is clearly better than the alternatives.
Activating the Mutual Assistance Clause of the Treaty on the European Union and the Right of Self-defence
Authors: Berdud Carlos Espaliú
Published: November 2019

Following the 2015 Paris attacks, one of the most discussed issues is whether the Paris incidents constitute an ‘armed attack’ requisite to trigger the right of self-defence in light of the wording of Article 51 of the UN Charter of 1945. Indeed, should the responses of the Member States to the Paris attacks, activating the mutual assistance clause, be seen as a move towards the formation of a new customary rule reshaping the content of the right of individual or collective self-defence in accordance with Article 51 of UN Charter and customary law? Or should that invocation of Article 42 (7) TEU be considered a violation of the UN Charter law of self-defence? This chapter examines the textual and contextual elements of Article 51 of the UN Charter and the practice of States since then, mainly in the context of the activity of the UN Security Council. After a careful examination of those elements, it concludes that if it can be said that the existing rule in international law in both conventional and customary law allowing states to have recourse to the use of force in self-defence can only be legally exercised in the presence of an armed attack committed by a state, it can be argued that the current practice of states appears to be heading in another direction. For the drafters of Article 51 of the UN Charter the right of self-defence was already ‘inherent’. If they had been in the current situation, they may have extended this right to cases of major terrorist attacks. In view of this context, the invocation of Article 42 (7) TEU in response to a serious terrorist attack, like those in Paris in November 2015, cannot be considered a violation of Article 51 of the UN Charter. Many of the EU Member States are prepared to entertain a new interpretation of that provision, at least that portion which respects the scope of the ratione personae.
The Crisis of Privacy and Sacrifice of Personal Data in the Name of National Security
Authors: Nesterova Irena
Published: November 2019

Edward Snowden’s surveillance revelations in 2013 raised the issue of privacy and security in the public spotlight. These revelations underlined the need for a strong data protection framework. At the same time, the pressing demand to address security concerns and the threat of terrorist attacks might weaken privacy and data protection standards. Two landmark judgments of the Court of Justice of the European Union, namely the Digital rights Ireland judgment (which invalidates the Data Retention Directive) and the Schrems judgment (which invalidates the Safe Harbour Decision forming a legal basis for transatlantic data transfers) are of great significance in strengthening the rights to privacy and data protection in the context of digital mass surveillance. They continue to have far-reaching implications for EU and national data retention mechanisms, as well on the cross-border data transfer framework. Through the lens of the CJEU, the chapter reveals the key challenges that data protection law faces both at national and EU level that have to be addressed in response to mass surveillance in order to maintain a proper balance between privacy and national security.
The Future We Want
Authors: Dubava Ilze
Published: November 2019

Sustainable development is currently acknowledged as a new paradigm in international investment protection law—to be taken into account when planning domestic investment policies and drafting future investment agreements. This chapter aims to provide a recontextualization of the current investment regime, integrating emphasis on protection of interests that go beyond sheer economic value in the application of investment law. To achieve this aim, this chapter incorporates two conceptual parts. The first provides an analysis of the term ‘economic development’ as the object and purpose of the existing international investment regime. The analysis suggests that economic development is a generic term whose meaning today must be contextualized by sustainable development, a concept that essentially seeks an equitable balance of economic development, social development, and environmental protection. Thus, sustainable development—being the recognized object and purpose of investment protection law today—requires equilibrium between the state’s regulatory responsibilities and the foreign investor’s interests. In the second part, the author suggests that, in pursuit of balance, sustainable development—again, the inherent objective of investment protection—may alter perceptions of applicable law and guide contextual and effective interpretations of investment protection standards towards a focus on wider interests than those of foreign investors alone. As a result, it may influence the methodologies that are used in order to establish violations of investment guarantees.
Personality
Authors: Nicholson Rowan
Published: November 2019

The purpose of this chapter is to produce a definition of the concept of personality in international law. It also discusses the meaning of such concepts as norms, facts, rights, and other legal relations. It draws on, among other things, the work of WN Hohfeld. The chapter defines an international legal person as an entity that is constructed as a fact by norms of international law and to which such norms give at least one right or duty in Hohfeld’s sense. This departs from definitions that treat personality as a ‘capacity’. It emphasizes instead that personality is about conduct: international law regulates conduct by persons towards other persons.
State-like entities in past eras of international law
Authors: Nicholson Rowan
Published: November 2019

This chapter is about the personality of state-like entities in eras before international law became an unquestionably global system—before, roughly, the early twentieth century. It focuses on differences between Western and non-Western entities in the preceding period, which present a number of intertwined complications. One of these is that Western ideas about international law were not familiar to or not accepted by state-like entities in Africa, Asia, and elsewhere, many of which had their own, incompatible ideas. Another is that Westerners dismissed these entities as insufficiently ‘civilized’ to participate fully in international law. The chapter concludes that, although both Western and non-Western entities have always had a degree of personality, it cannot be explained solely in terms of statehood in a clear technical legal sense.
Prolegomena
Authors: Perry Steven F. , Lambertz Markus , Schmitz Anke
Published: November 2019

Probably no process epitomizes life more than respiration. By respiration we mean the cascade of energy-producing biochemical reactions called oxidative phosphorylation, powered by a gradient of oxidation. Structure and function are intimately connected, forming an entity called a faculty. In this book, we focus on the functional and evolutionary morphology of the respiratory faculty, many of the components of which are older than the first animals, indeed older than life itself. The initial steps until the first animals arose are summarized here in a hypothetical scenario and provided together with an introduction to several other conceptual approaches that we have adhered to throughout this book.
Respiratory faculties of amphibious and terrestrial invertebrates
Authors: Perry Steven F. , Lambertz Markus , Schmitz Anke
Published: November 2019

This chapter focuses on the respiratory faculties of invertebrate air breathers. Although the partial pressure of oxygen in water is the same as in the surrounding atmosphere, the oxygen content per unit volume is around 30 times less due to its relatively low solubility in water. So it is no wonder that there is evidence for invertebrate animals on land as early as from the Palaeozoic. In spite of this apparent metabolic advantage, aside from some annelid groups, the only invertebrates to truly call dry land their home are some snails and arthropods. Among the latter, we see several independent origins of air breathing, and crustaceans present a particularly interesting study group in this regard. Arachnids and insects, on the other hand, were from the beginning terrestrial and air breathing, and insect tracheae form the most effective respiratory system going.
Respiratory faculties of amphibious and terrestrial craniotes
Authors: Perry Steven F. , Lambertz Markus , Schmitz Anke
Published: November 2019

This chapter introduces the ‘who has what’ in terms of air-breathing respiratory faculties for craniotes. Air breathing has arisen independently dozens of times among ray-finned fishes, but none has become completely terrestrial. The lobe-finned fishes eventually gave rise to amphibians and amniotes, and we see an increased importance of primarily lung-based air breathing. A muscular mechanism for lung ventilation (a buccal pump in amphibians and primarily a negative pressure aspiration mechanism in amniotes), pulmonary veins that return oxygenated blood to the heart, and some mechanism for partial or complete separation of oxygenated and deoxygenated blood masses at the heart are seen. Each major tetrapod group, in fact, has its own specific breathing mechanism. The chapter examines in some detail low-performance and high-performance faculties, the latter being particularly realized in the diaphragm-powered, ventilated pool system of the mammalian bronchoalveolar lung, and in the cross-current system of the avian lung–air sac system.
The evolution of water-breathing respiratory faculties in craniotes
Authors: Perry Steven F. , Lambertz Markus , Schmitz Anke
Published: November 2019

The major components of the respiratory faculty (gill structure, muscular ventilation, central heart and erythrocyte-containing blood, and pH-sensitive control of breathing) appear to have been present in craniotes from the very beginning. But the details are so different in the most basally radiating group, hagfish, corroborating that they separated very early from the stem line. In the other groups, progressive changes are seen in the structure of the gills, heart, haemoglobin, as well as in the control of breathing. In particular, a major and progressive change in gill structure is seen when comparing sharks to teleosts, with several intermediary forms realized.
The bottom line
Authors: Perry Steven F. , Lambertz Markus , Schmitz Anke
Published: November 2019

This chapter summarizes the most important aspects of the entire book. Writing an abstract of a summary can result in a ‘bouillon cube’ of information that is nearly incomprehensible, so this sticks to the most far-reaching observations and conclusions. The structure–function unit referred to here as the respiratory faculty did not just suddenly appear, but rather bits and pieces of it are recognizable even in most basally branching metazoan lineages. The use of mitochondria in an aerobic atmosphere to produce large amounts of energy-carrying molecules precipitated a kind of arms race, whereby the individuals that could compete better for food sources or become predatory could become part of an evolutionary cascade. These new animals moved into another realm, but the old ones did not necessarily disappear: they just did what they always did, maybe a little better. In the most diverse lineages of invertebrates and craniotes we see similar changes appearing: gills with counter-current exchange, highly specialized oxygen-carrying proteins, a partly or completely closed circulatory system that includes the gas exchange organs, lungs. The more extreme the grounds for specialization, the more similar are these structures and functions. Often the functional result remains unchanged or becomes improved while the anatomical cause changes dramatically, but just as often structures change little but minor functions become major ones: a phenomenon called exaptation. This book has looked at most major animal groups and these principles turn up everywhere. It talks about multidimensional forces at work in a multidimensional world, and respiration is the keystone to it all.
Contractarianism and the Moral Equality of Civilians
Authors: Benbaji Yitzhak , Statman Daniel
Published: November 2019

The chapter proposes a contractarian account of the strict prohibition against targeting civilians and of the limited permission to collaterally harm them. It shows that under an arrangement by which states hold armies whose role is self-defence and deterrence from aggression, a contract granting immunity to civilians from direct attack is mutually beneficial to all decent parties. It would immunize even civilians who are culpable for the threat against which the just side is fighting. The permission to inflict collateral damage on civilians is also explained on contractarian grounds. The chapter concludes by discussing the rules of warfare in asymmetrical conflicts.
Concluding Remarks
Authors: Benbaji Yitzhak , Statman Daniel
Published: November 2019

In this chapter we offer some concluding remarks. We point to the limitations of contractarianism, to its advantages over revisionism, and to its practicality. We show that for contractarianism wars are not necessarily ‘moral tragedies’, as they are for revisionists because wars do not necessarily involve unavoidable wrongdoing. According to contractarianism, combatants participating in war can do so without violating the rights of either combatants or civilians of the enemy side. The chapter also shows how even revisionists rely at times on contractualist premises to justify adherence to rules which they regard as unjustified in terms of ‘deep morality’. We also criticize the way this notion is utilized, especially the distinction between ‘deep morality’ and non-deep morality (associated with compliance with the laws of war). The distinction creates the impression that one should give priority to considerations stemming from deep morality over those stemming from shallow morality. But clearly, even revisionists do not assume such a priority—neither in general, nor in the field of war. Finally, the chapter highlights the ‘realist’ aspect of contractarianism, namely, its scepticism about the termination of wars and warfare. This scepticism has to do with the existence of evil individuals and of rogue states, but also with benign self-interest coupled with epistemic shortcomings and a constant suspicion of others. Given this realist assumption, states would be better off agreeing on rules to regulate war that would, on the one hand, facilitate effective self-defence, while on the other, reduce the killing and harm they cause.
Resettlement
Authors: Park Yoosun
Published: November 2019

Mere months after the opening of the camps, the War Relocation Authority instituted a scheme for the “permanent relocation” of the Nikkei outside the camps. Henceforth, all social work in the camps became oriented toward this end goal. Resettlement, actively supported by the YWCA and a host of social welfare organizations, was a project that provoked profound dread and anger in much of the incarcerated Nikkei. Social work agencies involved were cautioned to work quietly and inconspicuously to avoid public attention which would inevitably incite opposition from local populations. Resettlement was an assimilationist project, explicitly designed for the “decentralization” of the Nikkei to aid in their Americanization. Such goals of integration and assimilation were promoted in the camps through group work program designed to “counter Japanizing influences” of the Issei and “extend the Americanism” of the Nisei.
Conclusion
Authors: Park Yoosun
Published: November 2019

Social work equivocated. Social work organizations did not support mass removal, landing mostly on the stance that individual adjudication of loyalty rather than wholesale removal was the preferable course. But neither, on the whole, did they oppose wholesale removal, abdicating their right to and responsibility for contesting the wisdom of the government at war. Neither the disciplinary publications nor the archival records of workers in the field provide an unmitigated critique of the events. Even the YWCA, the best of social work in these events, followed the same racist schema that enabled the removal and incarceration. The history presented here is all the more disturbing because it is that of social workers doing what seemed to them to be more or less right and good.
One Health and Zoonotic Uncertainty in Singapore and Australia: Examining Different Regimes of Precaution in Outbreak Decision-Making
Authors: Degeling C , Gilbert G L , Tambyah P , Johnson J , Lysaght T
Published: November 2019

A One Health approach holds great promise for attenuating the risk and burdens of emerging infectious diseases (EIDs) in both human and animal populations. Because the course and costs of EID outbreaks are difficult to predict, One Health policies must deal with scientific uncertainty, whilst addressing the political, economic and ethical dimensions of communication and intervention strategies. Drawing on the outcomes of parallel Delphi surveys conducted with policymakers in Singapore and Australia, we explore the normative dimensions of two different precautionary approaches to EID decision-making—which we call regimes of risk management and organizing uncertainty, respectively. The imperative to act cautiously can be seen as either an epistemic rule or as a decision rule, which has implications for how EID uncertainty is managed. The normative features of each regime, and their implications for One Health approaches to infectious disease risks and outbreaks, are described. As One Health attempts to move upstream to prevent rather than react to emergence of EIDs in humans, we show how the approaches to uncertainty, taken by experts and decision-makers, and their choices about the content and quality of evidence, have implications for who pays the price of precaution, and, thereby, social and global justice.
Difference-in-Differences as an Alternative to Pretest–Posttest Regression for Social Work Intervention Evaluation and Research
Authors: Rose Roderick A , Bowen Natasha K
Published: November 2019

Nonrandomized evaluation designs are an important part of social work research because randomization is not always feasible in social work settings. Although randomly assigned groups are assumed to be equivalent, nonrandomly assigned groups are not. In nonrandomized settings, designs with multiple waves are ideal, but two-wave designs are still widely used. A common method for estimating a treatment effect in nonrandom two-wave designs is the pretest–posttest model. However, depending on relationships among participants and the method of assignment to treatment groups, researchers should consider a difference-in-differences approach to testing treatment effects. Authors describe and compare the pretest–posttest and difference-in-differences approaches and assumptions and offer guidelines, developed from a literature review, about the conditions under which each model is likely to be best. Authors also demonstrate the decision-making process and application of the methods in an evaluation of an elementary school intervention program.
A bispecific soluble receptor fusion protein that targets TNF‐α and IL‐21 for synergistic therapy in inflammatory arthritis
Authors: Park Jin‐Sil , Yoo Seok‐Ho , Lim Mi‐Ae , Ryu Jun‐Geol , Oh Hye‐Joa , Hwang Sun‐Hee , Yang SeungCheon , Jung Kyung‐Ah , Yoon Sunha , Park Bum‐Chan , Park Sung‐Hwan , Kim Ho‐Youn , Cho Mi‐La , Park Young‐woo
Published: November 2019

This study was aimed at investigating the therapeutic effects of BITRAP, a bispecific fusion protein targeting TNF‐α and IL‐21, on the development of autoimmune arthritis in humans and mice. To verify the effects of BITRAP in human, peripheral blood mononuclear cells were cultured with BITRAP under IL‐17‐producing T (Th17) cell‐polarizing conditions or osteoclast differentiation conditions. BITRAP treatment inhibited the production of IL‐17 and vascular endothelial growth factor but increased the production of IL‐10 in CD4+ T cells, as well as directly suppressed osteoclastogenesis. Collagen‐induced arthritis (CIA) and IL‐1R antagonist (IL‐1Ra) knockout mice were treated with BITRAP. Following injection in CIA mice, BITRAP rapidly migrated into the inflamed joints and remained there for 72 hours. Application of BITRAP attenuated the severity of autoimmune arthritis in CIA and IL‐1Ra knockout mice by reducing the numbers of inflammatory cytokine‐expressing cells and Th17 cells and antibody secretion. Finally, BITRAP suppressed STAT3 phosphorylation, as well as production of IL‐17 and TNF‐α, in murine splenic CD4+ T cells. These findings suggest that BITRAP, a bispecific fusion protein targeting TNF‐α and IL‐21, may be an effective treatment to overcome the limitations of anti‐TNF therapy for patients with rheumatoid arthritis.
Asymmetric functions of a binuclear metal center within the transport pathway of a human zinc transporter ZIP4
Authors: Zhang Tuo , Sui Dexin , Zhang Chi , Cole Logan , Hu Jian
Published: November 2019

Metal clusters are exploited by numerous metalloenzymes for catalysis, but it is not common to utilize a metal cluster for substrate transport across membrane. The recent crystal structure of a prototypic Zrt‐/Irt‐like protein (ZIP) metal transporter from Bordetella bronchiseptica (BbZIP) revealed an unprecedented binuclear metal center (BMC) within the transport pathway. Here, through a combination of bioinformatics, biochemical and structural approaches, we concluded that the two physically associated metal‐binding sites in the BMC of human ZIP4 (hZIP4) zinc transporter exert different functions: one conserved transition metal–binding site acts as the transport site essential for activity, whereas the variable metal–binding site is required for hZIP4's optimal activity presumably by serving as a secondary transport site and modulating the properties of the primary transport site. Sequential soaking experiments on BbZIP crystals clarified the process of metal release from the BMC to the bulky solvent. This work provides important insights into the transport mechanism of the ZIPs broadly involved in transition metal homeostasis and signaling, and also a paradigm on a novel function of metal cluster in metalloproteins.
Genome analysis-based reclassification of Enterobacter tabaci Duan et al. 2016 as a later heterotypic synonym of Enterobacter mori Zhu et al. 2011
Authors: Wu Wenjing , Zong Zhiyong
Published: November 2019

We performed a comparative genomic analysis to clarify the taxonomic relationship between the two

Enterobacter

species,

Enterobacter tabaci

and

Enterobacter mori

. Whole genome sequences of types strains of the two species became available recently. Average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH) between the two type strains were determined. Type strains of the two species had a 97.25 % ANI and an 80.4 % isDDH value, which are above the well-recognized cutoffs (≥95–96 % ANI and ≥70 % isDDH) for bacterial species delineation. The two strains have similar overall phenotypic characteristics and are clustered together with high bootstrap values in the multi-locus sequence analysis on rpoB, gyrB, infB and atpD housekeeping genes. It therefore becomes evident that the two species actually belong to the same species.

E. mori

has priority over

E. tabaci

, therefore we proposed that

E. tabaci

Duan et al. 2016 is a later heterotypic synonym of

E. mori

[]
Nitrincola tapanii sp. nov., a novel alkaliphilic bacterium from An Indian Soda Lake
Authors: Joshi Amaraja , Thite Sonia , Dhotre Dhiraj , Moorthy Manju , Joseph Neetha , Ramana V. Venkata , Shouche Yogesh
Published: November 2019

A novel Gram-stain-negative bacterial strain designated as MEB193T was isolated from a sediment sample collected from Lonar Lake, India. The cells were motile, non-spore-forming and rod-shaped. The strain was oxidase- and catalase-positive. It grew optimally at pH 9.0 and at 1 % (w/v) NaCl concentration at 30 °C. Based on 16S rRNA gene sequence similarity, MEB193T belongs to genus

Nitrincola

, with

Nitrincola alkalilacustris

ZV-19T (95.89 %) and

Nitrincola lacisaponensis

4CAT (95.87 %) as its closest neighbours. The major fatty acid was summed feature 8 comprising C18:1ω7c/C18:1ω6c (52 %) followed by C16 : 0 (25 %). Phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG) were present as the major polar lipids. The draft genome obtained in this study was 2 793 747 bp and the G+C content was 50.79 mol%. Average nucleotide identity (71.76 %) and DNA–DNA hybridization (<20 %) values between strain MEB193T and

Nitrincola lacisaponensis

4CAT confirmed the novelty of this new species. Based on phenotypic including chemotaxonomic and genotypic characterization data, strain MEB193T represents a new species of the genus

Nitrincola

for which the name Nitrincola tapanii sp. nov. is proposed. The type strain is MEB193T (=MCC 2863T=JCM 31570 T=KCTC 52390 T).
Structure-based design of a Cortistatin analog with improved immunoregulatory activity against inflammatory bowel disease (IBD)
Authors: Rol Álvaro , Todorovski Toni , Martin-Malpartida Pau , Escolà Anna , Gonzalez-Rey Elena , Aragón Eric , Verdaguer Xavier , Vallès-Miret Mariona , Farrera-Sinfreu Josep , Puig Eduard , Fernández-Carneado Jimena , Ponsati Berta , Delgado Mario , Riera Antoni , Macias Maria J.
Published: November 2019

Ulcerative colitis and Crohn’s disease are inflammatory bowel diseases (IBD) that lead to chronic inflammations of the gastrointestinal tract due to an abnormal response of the immune system. Finding new effective drugs to tackle IBD represents a major therapeutic concern since IBD incidence and prevalence is increasing worldwide. Recent studies positioned Cortistatin (CST) as a candidate for IBD treatment due to its anti-inflammatory and immunomodulatory activity. Here, we studied the structural properties of CST using NMR and synthesized and characterized new analogs displaying enriched populations of some native conformations. One of them, Analog 5, preserved the activity against IBD with an increased half-life in serum, overcoming the native hormone limitation and opening the door for the use of CST analogs as therapeutic agents. This work represents a new approach to the rational design of molecules to treat IBD and a possibility for patients that fail to respond to other therapies.

Graphical abstract
Meta-control of the exploration-exploitation dilemma emerges from probabilistic inference over a hierarchy of time scales
Authors: Marković Dimitrije , Goschke Thomas , Kiebel Stefan J.
Published: November 2019

Cognitive control is typically understood as a set of mechanisms which enable humans to reach goals that require integrating the consequences of actions over longer time scales. Importantly, using routine beheavior or making choices beneficial only at a short time scales would prevent one from attaining these goals. During the past two decades, researchers have proposed various computational cognitive models that successfully account for behaviour related to cognitive control in a wide range of laboratory tasks. As humans operate in a dynamic and uncertain environment, making elaborate plans and integrating experience over multiple time scales is computationally expensive, the specific question of how uncertain consequences at different time scales are integrated into adaptive decisions remains poorly understood. Here, we propose that precisely the problem of integrating experience and forming elaborate plans over multiple time scales is a key component for better understanding how human agents solve cognitive control dilemmas such as the exploration-exploitation dilemma. In support of this conjecture, we present a computational model of probabilistic inference over hidden states and actions, which are represented as a hierarchy of time scales. Simulations of goal-reaching agents instantiating the model in an uncertain and dynamic task environment show how the exploration-exploitation dilemma may be solved by inferring meta-control states which adapt behaviour to changing contexts.
Maternal Effect Senescence and Fitness: A Demographic Analysis of a Novel Model Organism
Authors: Hernández Christina M. , van Daalen Silke F. , Caswell Hal , Neubert Michael G. , Gribble Kristin E.
Published: November 2019

Maternal effect senescence—a decline in offspring fitness with maternal age—has been demonstrated in a range of taxa, including humans. Despite decades of phenotypic studies, it remains unclear how maternal effect senescence impacts population structure or evolutionary fitness. To understand the impact of maternal effect senescence on population dynamics, fitness, and selection, we used data from individual-based culture experiments on the microscopic aquatic invertebrate,Brachionus manjavacas(Rotifera), to develop a series of matrix population models in which individuals are classified jointly by age and maternal age. By comparing the results derived from models with and without maternal effects, we found that the fitness difference due to maternal effect senescence arises primarily through decreased fertility, particularly at maternal ages corresponding to the peak reproductive output. In all models, selection gradients decrease with increasing age. They also decrease with maternal age for large maternal ages, implying that maternal effect senescence can evolve through the same process as in Hamilton’s theory of the evolution of demographic senescence. We find that maternal effect senescence significantly alters population structure and fitness forB. manjavacas, a species with high maternal investment and maximum reproduction in early-to mid-life. The models developed here were built with data from an emerging model organism, and are widely applicable to evaluate the fitness consequences of maternal effect senescence across species with diverse aging and fertility schedule phenotypes.
Adolescent substance use and functional connectivity between the ventral striatum and hippocampus
Authors: Huntley Edward D. , Marusak Hilary A. , Berman Sarah E. , Zundel Clara G. , Hatfield Joshua R.B. , Keating Daniel P. , Rabinak Christine A.
Published: November 2019

Neurodevelopmental explanations for adolescent substance use have focused on heightened sensitivity of the brain’s reward system, centered around the ventral striatum (VS). Recent evidence demonstrates increased functional connectivity between the VS and hippocampus in adolescents relative to adults, suggesting that the adolescent brain may learn from subsequent exposure to risks/rewards. However, a link between VS-hippocampal circuitry and adolescent substance use has yet to be established. Two separate longitudinal studies were conducted to evaluate whether variation in VS-hippocampal resting-state functional connectivity (rs-FC) predicts subsequent adolescent substance use. Study 1 consisted of 19 youth recruited from a high sociodemographic risk population (N = 19; 14 female; 47% Black Non-Hispanic, 32% White Non-Hispanic). To replicate results of Study 1, Study 2 utilized data from the National Consortium on Adolescent Neurodevelopment and Alcohol, an ongoing multi-site imaging study (N= 644; 339 female; 11% Black Non-Hispanic, 11% Hispanic/Latino, 66% White Non-Hispanic). Resting-state fMRI data were collected at a baseline time point and lifetime and past year self-reported substance use was collected at a follow up visit. Regression models tested whether baseline VS-hippocampal rs-FC predicted substance use at follow up. Across both studies, higher VS-hippocampal rs-FC at baseline predicted greater substance use at follow up. These data provide the first evidence linking increased VS-hippocampal connectivity with greater adolescent substance use. Results fit with the emerging idea that adolescent substance use is driven by not only a heightened sensitivity to reward, but also a stronger link between reinforcement learning and episodic memory for rewarding outcomes.
Analytical solution for a hybrid Logistic-Monod cell growth model in batch and CSTR culture
Authors: Xu Peng
Published: November 2019

Monod and Logistic growth models have been widely used as basic equations to describe cell growth in bioprocess engineering. In the case for Monod equation, specific growth rate is governed by a limiting nutrient, with the mathematical form similar to the Michaelis-Menten equation. In the case for Logistic equation, specific growth rate is determined by the carrying capacity of the system, which could be growth-inhibiting factors (i.e. toxic chemical accumulation) other than the nutrient level. Both equations have been found valuable to guide us build structure-based kinetic models to analyze fermentation process and understand cell physiology. In this work, we present a hybrid Logistic-Monod growth model, which accounts for multiple growth-dependence factors including both the limiting nutrient and the carrying capacity of the system. Coupled with substrate consumption and yield coefficient, we present the analytical solutions for this hybrid Logistic-Monod model in both batch and CSTR culture. Under high biomass yield (Yx/s) conditions, the analytical solution for this hybrid model is approaching to the Logistic equation; under low biomass yield condition, the analytical solution for this hybrid model converges to the Monod equation. This hybrid Logistic-Monod equation represents the cell growth transition from substrate-limiting condition to growth-inhibiting condition, which could be adopted to accurately describe the multi-phases of cell growth and may facilitate kinetic model construction, bioprocess optimization and scale-up in industrial biotechnology.