bluuebunny/crossref_metadata_2025 huggingface dataset:
Divine and Human Agency in Calvin’s Institutes
Authors: Theus Emily
Published: July 2021

This chapter considers the doctrines of providence and sin in the Institutes of Christian Religion in order to draw out Calvin’s views on the interplay of human and divine agency. Calvin’s account of God’s particular providence establishes the basic conditions for human responsibility and characterizes God’s agency as perfectly efficacious—so much so that the relationship between God’s willing and evil/sin cannot adequately be captured through language of ‘permission’. The doctrine of sin further inflects this account, clarifying the relationship between human freedom, necessity, and responsibility for sin. The result is a challenging picture, in which humans are responsible for sin, but not for good, and in which God is causally determinative of both good and evil. The key to this account—to understanding its perplexities and to identifying what features of meaningful human action are at stake—is the nesting of intentions within a layering of human and divine agency.
Calvin and Equity
Authors: Batson Alexander
Published: July 2021

This chapter argues that the concept of equity plays a crucial role in Calvin’s early writings, especially in the Commentary on Seneca and the 1536 edition of the Institutes. Calvin embraces two distinct yet inseparable meanings of the term ‘equity’. One sense is as an interpretative principle of natural law, and the goal at which all civil law aims. The other sense is an application of the interpretative sense, in which a ruler or judge amends a civil law that is too strict or too general to take into account all the particularities of a certain case. Calvin’s concept of equity displays both his humanist legal training as well as the critical place of natural law in his theology.
Cromwellian Calvinism
Authors: Powell Hunter
Published: July 2021

When England’s Parliament rejected enforced Presbyterian conformity in 1648, it was because English Calvinism was never comfortable with elevating polity to a matter of confession. During the Interregnum (1649–1660) former Westminster divines (led by the now ascendant Congregationalists) sought to define orthodoxy for Oliver Cromwell’s state church. They tried repeatedly to strike a balance between enforcing confessional subscription for parish ministers, while still allowing a limited accommodation for those who could not or who would not submit—provided they did not preach or publish against those statements of faith. In the face of growing sectarianism, each confessional attempt saw an increasingly robust (and thus restrictive) Calvinism culminating in the last confession of the Puritan era, the Savoy Declaration.
Calvin and Calvinism in Germany
Authors: Ocker Christopher
Published: July 2021

Calvin’s experience of Germany was limited and partial, but his theology played an important role there. It came to be associated with a kind of Protestant internationalism, while specific points of his doctrine formed a polemical cypher used by some German Lutherans, many in the service of imperial princes, against Philip Melanchthon in the last decade of his life and against Melanchthon’s students in the next generation. In the second half of the sixteenth century, the effort to build a Lutheran identity at peace with the Holy Roman Empire’s complex political and religious subsidiarity made ‘Calvinism’ its contrary and reified German ‘Calvinism’ as a polemical glyph. Out of political and doctrinal turmoil, the ‘Reformed’ territorial churches of Germany emerged. These churches were finally recognized in the Peace of Westphalia (1648), but eventually they yielded to a national Protestant church in the nineteenth century. In short, the history of Calvinism in Germany was marked by a complex, evolving fusion of doctrinal differentiations and imperial politics.
John Calvin, Bernardino Ochino, and Italian ‘Heretics’
Authors: Camaioni Michele
Published: July 2021

Until recently, scholars have often framed the relationship between John Calvin and the radical wing of the Italian Reformation through the lens of a dialectical and rather violent clash. Springing from different cultural backgrounds, this confrontation reached its peak after the condemnation of the anti-trinitarian Michael Servetus in Geneva (1553), when some Italian exiles religionis causa gathered in Basel to express a sharp criticism towards Calvin’s intransigence and dogmatism in dealing with internal dissent. Recent works have led to a deconstruction of this enduring interpretation and offered a more complex view of Calvin’s personality, theology, and agency. As the chapter shows, such a problematizing approach inspires a less teleological reading of the ambiguous but rich entanglement between the Genevan Reformer and the Italian ‘heretics’, suggesting that, through the confrontation with the sceptical rationalism and the elusive spiritualism of his critics, Calvin’s theology reached its full maturity and clarity of expression.
Electoral Accountability and Corruption
Authors: Bågenholm Andreas
Published: July 2021

This chapter reviews the rapidly expanding literature on the electoral effects of corruption. A general finding is that corrupt parties and politicians get punished by voters at elections, but oftentimes not harshly enough to remove them from office. This chapter firstly elaborates how the electoral accountability mechanism is ideally supposed to work. It then looks at the extent to which corrupt elected representatives get punished and how different types of studies seem to systematically reach different conclusions in this respect. Thereafter, the by now quite substantial body of research on the reasons why corruption voting takes place is discussed, after which the much more limited literature on the connection between electoral accountability and levels of corruption is reviewed. The chapter ends with some ideas of how to move forward within this field of research.
Quality of Government and Political Support
Authors: Linde Jonas , Dahlberg Stefan
Published: July 2021

This chapter provide an overview of the growing stock of research on the relationship between quality of government and political support. After having been surprisingly absent from the research agenda dealing with support and legitimacy, a growing number of studies have come to demonstrate the importance of impartiality in the implementation of public policies for political support and democratic legitimacy. After outlining a framework for analysis of political support and a discussion of different aspects of quality of government in this body of research, we take a closer look on a number of important contributions that have demonstrated the explanatory power of quality of government when it comes to analyses of variation in political support. In doing so, we distinguish between studies that have assessed the effects of quality of government on the system level (e.g. countries’ level of corruption) and analyses investigating the relationship between individuals’ perceptions of the quality of government and political support.
Social Accountability and Quality of Government
Authors: Boräng Frida , Grimes Marcia
Published: July 2021

The idea of meeting government failures with social accountability reforms has gained enormous traction. This chapter surveys the existing empirical and theoretical accounts of institutional arrangements designed to empower citizens to hold incumbents and government officials accountable, with a focus on the potential for such initiatives to improve QoG. Empirically, the evidence reviewed suggests that social accountability initiatives are less transformative than hoped, often more effective for detecting leakage than rectifying problems or holding officials to account. The chapter focuses theoretically on what SAIs entail for participants in terms of effort, coordination with others, and expected gains, as well as how contextual conditions affect the functioning of SAIs. While existing research examines contextual conditions, we offer theoretical arguments and empirics from the areas of political economy and institutionalism suggesting that context, and in particular aspects of state capacity, can affect participants’ priors, and thus SAIs success, in ways that warrants further investigation.
Civil Society against Corruption
Authors: della Porta Donatella , Mattoni Alice
Published: July 2021

In the last decades, several types of civil society actors have mobilized against corruption all over the world, at the transnational, national, and local level. The chapter discusses these anticorruption efforts in order to understand their main features, challenges, and potential future developments. The chapter is structured as follows: after a general introduction, the first section reflects on how literature on corruption has dealt with civil society actors. The second section examines the types of actors that engage in collective action, the types of collective action that they employ, and the types of frames that they use to interpret the present situation and to imagine future societies. The third section illustrates some of the key conditions for the development of anticorruption efforts from the grassroots. The fourth section discusses the consequences of civil society’s efforts against corruption. Conclusions focus on future lines of investigation on the struggle of civil society against corruption.
The Quality of Government and Economic Growth
Authors: Ahlerup Pelle , Baskaran Thushyanthan , Bigsten Arne
Published: July 2021

This chapter reviews the literature on the relationship between the quality of government (QoG) and economic growth. As there is limited evidence on the link between QoG narrowly defined and growth, our focus is on the role of related aspects, such as democracy, formal institutions, and cultural norms. We discuss institutional challenges in generating and sustaining high growth rates. We then review the evidence on how QoG, and related aspects of political and economic life, affect growth and pay attention to the relevant channels. We also discuss whether it is harder to sustain growth if it increases inequality. Since a government needs to be both efficient and impartial to support aggregate economic performance, we argue that it is too strict to let QoG be defined as impartiality only.
Controlling Corruption
Authors: Johnston Michael
Published: July 2021

Institutional checks on corruption are central to virtually every reform strategy, but they do not come in any standard form, and are unlikely to succeed in isolation. Some are aimed primarily at bureaucratic corruption, some more at political corruption, and some of the most important operate in both realms. Anticorruption agencies (ACAs) have been established—sometimes repeatedly—in around a hundred societies but have an indifferent track record. They are most likely to succeed when supported by a range of other strong governing institutions. Transparency is also a common institutional reform, and it too has consequences that are varying and contingent on local and cross-border influences. Conflict of interest legislation, and whistleblower protections, are also important issues in numerous societies. Specific institutional controls, in the end, require sound supportive institutions of several sorts; even then, the political, economic, and social challenges of corruption control remain formidable.
Bureaucracy and Government Quality
Authors: Dahlström Carl , Lapuente Victor
Published: July 2021

How does the way the bureaucracy is organized affect the quality of the public policies delivered? This chapter focuses primarily on the role of human resources in the public sector and its impact on good government. We argue it is specifically important how bureaucrats are recruited, promoted, dismissed, and incentivized; what public administration scholars refer to as “civil service systems.” Building on the more than 75-year-old discussion between Carl Friedrich (1940) and Herman Finer (1941), we explore the pros and cons of having public employees who are directly accountable to their political masters vis-à-vis public employees who are politically autonomous. The review of the available evidence indicates that, all other things being equal, civil servants’ autonomy leads to less corrupt, and more effective governments in comparison with polities where civil servants owe their positions to political connections. The chapter concludes that civil servants should be directly accountable to their professional peers instead of their political superiors.
Organized Crime and the Quality of Government
Authors: Holmes Leslie
Published: July 2021

Until the 1990s, organized crime (OC) was usually treated by both states and analysts as a form of criminality, but not a political phenomenon. The situation has changed since the end of the Cold War, however, and OC is now typically seen as both a security threat and a political actor that can impact upon the quality of government. Reasons for this change are explored in this chapter. Arguably, OC becomes the most dangerous when it colludes with corrupt state officials and even the state itself. Following sections on defining terms and how perceptions have changed since 1990, this chapter provides a novel taxonomy of the numerous ways in which OC and the state interact—and in some cases even mimic each other. The chapter concludes with consideration of the impact that collusion and mimicry have on the quality of government, and an agenda for future research.
What Can We Learn about Corruption from Historical Case Studies?
Authors: Knights Mark
Published: July 2021

The chapter shows how a historical approach can offer a productive and useful dataset and tools to understand corruption and anticorruption. Since corruption has existed across time and space, and is multifaceted, involving politics, economics, law, administration, social, and cultural attitudes, it can best be studied in a multidisciplinary way that includes the study of the past as well as the present. A historical approach offers ways of thinking about change and continuity, and hence also about how and why reform processes occur and are successful. Historical case studies can test and challenge social science models but also offer different, more qualitative, evidence that can help us to reconstruct the mentalities of those who refused to accept that their behavior constituted “corruption,” as well as the motives of those bringing the prosecution or making allegations. Historical sources, often offering multiple perspectives of different participants, can also enable us to form a more holistic view of corruption scandals and of the important role of public discussion in shaping quality of government.
Coptic
Authors: Papaconstantinou Arietta
Published: July 2021

Through the lens of translation, this sub-chapter discusses the broader relation between Coptic and Greek literature in Egypt. It highlights a series of other processes through which the two cultures engaged with each other and argues for a much more complex phenomenon than that of a one-way reception. Greek Christian literature was indeed essential to the formation of Coptic literary sensitivity, and literature in Coptic follows the norms and genres of the Greek canon, albeit often in a creative and original way. At the same time, Egyptian monastic tropes ultimately found their way into the heart of medieval Byzantine culture. The sub-chapter follows this process of cross-fertilization from the fourth century until the early centuries of Arab rule in the country, when Greek texts were still written, and Greek manuscripts were kept in Egyptian monasteries.
Language
Authors: Hinterberger Martin
Published: July 2021

Byzantine Greek was a highly developed and artful language with close ties both to the living language of the time and to a centuries-old literary heritage. Like all humans, the Byzantines grew up with their mother tongue; for those of Greek-speaking background and in Greek-speaking contexts, this was the spoken medieval Greek. Those who had the privilege to obtain education adopted—to various degrees—linguistic elements of older stages of the Greek language in order to compose their texts. Many of these older linguistic elements were used in a seemingly “arbitrary” way when compared to the linguistic rules of ancient Greek. Viewed in their contemporary context, however, these elements were creatively incorporated into a linguistic system which was essentially based on the contemporary language and was consistent in itself. The creative blend of traditional and modern features—though not readily accessible to the modern reader—and the tension between them left ample space for personal choices. This is precisely what makes the language of Byzantine literature a particularly exciting topic.
Georgian
Authors: Aleksidze Nikoloz
Published: July 2021

The chapter introduces two texts that entered the Greek writing through the Georgian medium. These are Barlaam and Ioasaph and the Passion of Michael of Mar Saba, both likely translated into Greek by Euthymios Hagiorites, the Georgian abbot of the Iveron Monastery on Mount Athos. The Greek Barlaam and Ioasaph was traditionally often attributed to Ioannes Damaskenos; however, since Paul Peeters’s study, it has been convincingly argued that it was translated from the Georgian Balavariani by the late tenth or early eleventh century. The “Georgian” provenance of the Passion of Michael of Mar Saba still remains debatable due to significant divergences between the Greek and Georgian versions; however, there remain internal and external factors that point to Mount Athos and Euthymios as the origin of the Greek version.
Arabic
Authors: Messis Charis , Papaioannou Stratis
Published: July 2021

The chapter surveys Christian Arabic literature translated into Greek as well as “Eastern” storytelling that was mediated through Arabic and reached the Byzantine Greek tradition through translation. It thus discusses (a) texts written in the context of so-called Melkite communities in the wake of the Islamic conquests as well as, later, in the Byzantine environment of Antioch from 969 to 1084 (e.g., the Life of Ioannes Damaskenos [BHG 884]); and (b) the transmission and translation history of Barlaam and Ioasaph (the life of Buddha), Stephanites and Ichnelates (Kalīla wa Dimna), and Syntipas (The Book of Sindbad), as well as the possible links with Arabic storytelling of Digenis Akrites. It also draws attention to translations made in the courtly environment of the late Byzantine empire of Trebizond.
Poetry?
Authors: Bernard Floris , Demoen Kristoffel
Published: July 2021

This chapter gives an overview of how Byzantines conceptualized “poetry.” It argues that from the Byzantine point of view, poetry only differs from prose in a very formal way, namely that it is written in verse. Both prose and poetry belonged to the category of logoi, the only label that was very frequently used, in contrast to the term “poetry,” which was reserved for the ancient poetry studied at schools. Many authors considered (and exploited) the difference between their own prose texts and poems as a primarily formal one. Nevertheless, poetry did have some functions that set it apart from prose, even if these features are for us less expected. The quality of “bound speech” gained a spiritual dimension, since verse was seen as a restrained form of discourse, also from a moral point of view. Finally, the chapter gives a brief overview of the social contexts for which (learned) poetry was the medium of choice: as an inscription, as paratext in a wide sense, as a piece of personal introspection, as invective, as summaries (often of a didactic nature), and as highly public ceremonial pieces.
Syriac
Authors: Ubierna Pablo
Published: July 2021

The chapter presents a general overview of Syriac texts which were translated into Greek. From the fourth to the sixth century, one encounters primarily classics of Syriac patristic literature (such as Ephrem the Syrian) and various hagiographical texts. After the seventh century, Greek translations from Syriac were limited to a few texts: the mystical writings of Isaak the Syrian and an Apocalypse related to the rise of Islam, and pseudonymously attributed to Methodios bishop of Olympos.
What Is Byzantine Literature?
Authors: Papaioannou Stratis
Published: July 2021

The chapter raises the question of what is “Byzantine literature” and introduces the contents of the Handbook. In the context of the volume, “Byzantine literature” refers to “Literature in Greek, during the Byzantine period (330 ce–1453 ce),” which, however, raises a series of problems. (1) While “literature,” for a modern audience, signifies primarily fiction and poetry, a wider understanding of the term is needed so as to appreciate the manifold textual and discursive culture of Byzantium as we can recover it from the thousands of manuscripts and inscriptions in which it has been preserved (relevant statistics are also offered). (2) While “Byzantine” has been conventionally used in order to focus on Greek literature (in the predominantly Greek-speaking “Byzantine” Empire), this should not make us forget that Greek was only one among many “Byzantine” languages (e.g., Latin, Coptic, Syriac, Georgian, and Arabic) and that the relation of the Greek tradition with the literary traditions in these other languages is fundamental for understanding Byzantine literature in its totality.
Sacred Song
Authors: Papaioannou Stratis
Published: July 2021

The chapter surveys the primary forms that Christian sacred song took in Byzantium, in relation to the relevant manuscript evidence, liturgical practice, and music. It first draws attention to major challenges in relevant research (e.g., the immensity of the evidence, the living tradition of Byzantine liturgy, the disparate nature of the available evidence). Then, the main hymnic forms are presented: the monostrophic troparion, the polystrophic kontakion (for whose later history the chapter proposes an innovative reinterpretation of its supposed “decline” during the middle Byzantine period), the polystrophic kanôn, and the polystrophic stichêra. The chapter concludes with a presentation of various fields of desiderata in the study of Byzantine hymnography.
Syriac
Authors: Ubierna Pablo
Published: July 2021

During late antiquity, Syriac, a dialect of Aramaic, belonging to the northwest group of Semitic languages, and originally the language of the Kingdom of Edessa and the Oshroene in Upper Mesopotamia, became the literary language of Aramaic-speaking Christians and developed under the mutual influences of both Greek and Iranian. This section surveys Syriac translations of Byzantine Greek texts, from the Bible and homiletics, to theological and ascetic literature, as well as historiographical, hagiographical, and other narrative texts. It thus highlights Greek authors with important corpora in Syriac (e.g. Gregory the Theologian, John Chrysostom, and the Areopagitic corpus), as well as authors and texts no longer extant in Greek (often because of their deviation from Constantinopolitan orthodoxy).
Rhetorical Practice
Authors: Riehle Alexander
Published: July 2021

This chapter surveys key aspects of rhetorical practice in Byzantium, with a focus on the middle and late periods. The first section maps out the generic landscape of Byzantine rhetoric, which, in addition to oratory in the narrow sense, can be argued to comprise virtually all of (highbrow) literature, including poetry. While it is true that Byzantine rhetoric is particularly rich in texts of the demonstrative type such as encomia, the essay asserts against claims to the contrary, that forms of deliberative and judicial rhetoric continued to exist in Byzantium and appear in fact ubiquitously once one broadens the scope beyond secular oratory. After a brief sketch of the place of rhetoric in higher education, the chapter proceeds to discuss the various steps involved in composing and performing a rhetorical text. In this, it follows ancient and medieval precepts for the so-called tasks of the rhetorician—invention, arrangement, style, memory and delivery—and shows their relevance for the practice of writing and reciting texts belonging to various rhetorical genres. Throughout, this chapter argues that scholarship on Byzantine rhetoric has focused too narrowly on panegyric and on matters of style, and that attention should turn to long-neglected aspects of argumentative technique that were at the heart of Byzantine rhetorical theory and education and that can be found in a wide array of textual genres, particularly in religious literature.
Stress response proteins NRP1 and NRP2 are pro-survival factors that inhibit cell death during ER stress
Authors: Yang Yuhua , Liu Xu , Zhang Wenbin , Qian Qian , Zhou Limeng , Liu Shu , Li Yuge , Hou Xingliang
Published: July 2021

Environmental stresses cause an increased number of unfolded or misfolded proteins to accumulate in the endoplasmic reticulum (ER), resulting in ER stress. To restore ER homeostasis and survive, plants initiate an orchestrated signaling pathway known as the unfolded protein response (UPR). Asparagine-rich protein (NRP) 1 and NRP2, two homologous proteins harboring a Development and Cell Death domain, are associated with various stress responses in Arabidopsis (Arabidopsis thaliana), but the relevant molecular mechanism remains obscure. Here, we show that NRP1 and NRP2 act as key pro-survival factors during the ER stress response and that they inhibit cell death. Loss-of-function of NRP1 and NRP2 results in decreased tolerance to the ER stress inducer tunicamycin (TM), accelerating cell death. NRP2 is constitutively expressed while NRP1 is induced in plants under ER stress. In Arabidopsis, basic leucine zipper protein (bZIP) 28 and bZIP60 are important transcription factors in the UPR that activates the expression of many ER stress-related genes. Notably, under ER stress, bZIP60 activates NRP1 by directly binding to the UPRE-I element in the NRP1 promoter. These findings reveal a pro-survival strategy in plants wherein the bZIP60–NRPs cascade suppresses cell death signal transmission, improving survival under adverse conditions.
Effect of farrowing pen size on pre-weaning performance of piglets
Authors: Vande Pol Katherine D , Laudwig Austin L , Gaines Aaron M , Peterson Beau A , Shull Caleb M , Ellis Michael
Published: July 2021

Litter sizes in commercial pig production have increased substantially over recent years; however, farrowing pen sizes have generally not changed over the same time period. The objective of this study was to evaluate the effect of farrowing pen size on piglet pre-weaning growth and mortality. Differences in pen size were created by varying the width of pens of the same length, increasing the creep area available to the piglets. The study used a total of 1,786 litters in a randomized complete block design to compare two farrowing pen size treatments (FPS): Standard (pen width 1.52 m) and Increased (pen width 1.68 m). Litter sizes were equalized across treatments (12.9 ± 1.95 piglets) at 24 h after birth using cross-fostering. Litter weights were collected at birth and weaning (21.3 ± 2.08 d); pre-weaning mortality was recorded. The experimental unit was the litter; models for statistical analysis included FPS and replicate. Farrowing pen size had no effect (P > 0.05) on litter size at birth (12.8 and 13.0 for the Standard and Increased FPS, respectively), after cross-fostering (12.9 for both treatments), or at weaning (11.2 and 11.3, respectively). There was no effect (P > 0.05) of FPS on total litter or average piglet weight at birth, after cross-fostering, and at weaning. These results suggest no benefit in piglet performance from increasing the width of farrowing pens. As litter sizes continue to increase in commercial production, further research is warranted to re-evaluate the impact of farrowing pen size on pre-weaning mortality.
Submicron silica particles have cytotoxicities on hepatocellular carcinoma, non-small cell lung cancer and breast cancer by unified regulating the XLOC_001659/miR-98-5p/MAP3K2-mediated pathway
Authors: Shi Jingdong , Ci Yukun , Zheng Ying , Chen Wenhui , Chen Xi
Published: July 2021

The cytotoxicities of silica (SiO2s) particles against cancers are still controversial. In this study, the purchased submicron silica particles (SM-SiO2s) were identified by transmission electron microscopy and energy dispersive spectrometer, and it showed potent cytotoxicities on hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) and breast cancer (BC), which ranked the top in the incidence among the tumor types. Through the microarray assay on long noncoding RNAs (lncRNAs) from the SM-SiO2s-treated HCC, NSCLC and BC cells, followed by Venn analysis, we found that a series of lncRNAs were significantly regulated by SM-SiO2s, among of which XLOC_001659 was mostly decreased. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay confirmed that XLOC_001659 could be decreased in all the SM-SiO2s-treated HCC, NSCLC and BC cells, coupled to inhibited cell proliferation. Further, XLOC_001659 was recognized as a miR-98-5p sponge and therefore modulates the “pro-inflammatory tumor promoter” MAP3K2 expressions. The XLOC_001659/miR-98-5p/MAP3K2 axis uniformly mediated the regulation of SM-SiO2s on proliferation of HCC, NSCLC and BC cells. Further clinical experiments demonstrated that XLOC_001659 was negatively correlated with miR-98-5p level and positively correlated with MAP3K2 level, and XLOC_001659/miR-98-5p/MAP3K2 axis was significantly associated with progressions and prognosis in HCC, NSCLC and BC patients. These results provide a new clue for the anti-tumor mechanism of SM-SiO2s and a new way for drug development by using SM-SiO2s.
Estimating Hepatotoxic Doses Using High-Content Imaging in Primary Hepatocytes
Authors: Shah Imran , Antonijevic Todor , Chambers Bryant , Harrill Joshua , Thomas Russell
Published: July 2021

Using in vitro data to estimate point of departure (POD) values is an essential component of new approach methodologies (NAMs)-based chemical risk assessments. In this case study, we evaluated a NAM for hepatotoxicity based on rat primary hepatocytes, high-content imaging (HCI), and toxicokinetic modeling. First, we treated rat primary hepatocytes with 10 concentrations (0.2–100 µM) of 51 chemicals that produced hepatotoxicity in repeat-dose subchronic and chronic exposures. Second, we used HCI to measure endoplasmic reticulum stress, mitochondrial function, lysosomal mass, steatosis, apoptosis, DNA texture, nuclear size, and cell number at 24, 48, and 72 h and calculated concentrations at 50% maximal activity (AC50). Third, we estimated administered equivalent doses (AEDs) from AC50 values using toxicokinetic modeling. AEDs using physiologically based toxicokinetic models were 4.1-fold (SD 6.3) and 8.1-fold (SD 15.5) lower than subchronic and chronic lowest observed adverse effect levels (LOAELs), respectively. In contrast, AEDs from ToxCast and Tox21 assays were 89.8-fold (SD 149.5) and 168-fold (SD 323.7) lower than subchronic and chronic LOAELs. Individual HCI endpoints also estimated AEDs for specific hepatic lesions that were lower than in vivo PODs. Lastly, AEDs were similar for different in vitro exposure durations, but steady-state toxicokinetic models produced 7.6-fold lower estimates than dynamic physiologically based ones. Our findings suggest that NAMs from diverse cell types provide conservative estimates of PODs. In contrast, NAMs based on the same species and cell type as the adverse outcome may produce estimates closer to the traditional in vivo PODs.
Turgor-limited predictions of tree growth, height and metabolic scaling over tree lifespans
Authors: Potkay Aaron , Hölttä Teemu , Trugman Anna T , Fan Ying
Published: July 2021

Increasing evidence suggests that tree growth is sink-limited by environmental and internal controls rather than by carbon availability. However, the mechanisms underlying sink-limitations are not fully understood and thus not represented in large-scale vegetation models. We develop a simple, analytically solved, mechanistic, turgor-driven growth model (TDGM) and a phloem transport model (PTM) to explore the mechanics of phloem transport and evaluate three hypotheses. First, phloem transport must be explicitly considered to accurately predict turgor distributions and thus growth. Second, turgor-limitations can explain growth-scaling with size (metabolic scaling). Third, turgor can explain realistic growth rates and increments. We show that mechanistic, sink-limited growth schemes based on plant turgor limitations are feasible for large-scale model implementations with minimal computational demands. Our PTM predicted nearly uniform sugar concentrations along the phloem transport path regardless of phloem conductance, stem water potential gradients and the strength of sink-demands contrary to our first hypothesis, suggesting that phloem transport is not limited generally by phloem transport capacity per se but rather by carbon demand for growth and respiration. These results enabled TDGM implementation without explicit coupling to the PTM, further simplifying computation. We test the TDGM by comparing predictions of whole-tree growth rate to well-established observations (site indices) and allometric theory. Our simple TDGM predicts realistic tree heights, growth rates and metabolic scaling over decadal to centurial timescales, suggesting that tree growth is generally sink and turgor limited. Like observed trees, our TDGM captures tree-size- and resource-based deviations from the classical ¾ power-law metabolic scaling for which turgor is responsible.
Bromodomain and extraterminal domain protein bromodomain inhibitor based cancer therapeutics
Authors: Halder Tithi Ghosh , Soldi Raffaella , Sharma Sunil
Published: July 2021

Purpose of review

Bromodomain and extraterminal domain (BET) proteins are evolutionarily conserved, multifunctional super-regulators that specifically recognize acetyl-lysine on histones and other proteins controlling gene transcription. Several studies show that small molecules targeting these regulators preferentially suppress the transcription of cancer-promoting genes. Consequently, several BET inhibitors reached clinical trials and are in various stages for different kind of malignancies. In this review, we provide a concise summary of the molecular basis and preliminary clinical outcomes of BET inhibitors as anticancer therapeutics.

Recent findings

Results from early clinical trials with BET inhibitors confirmed their antitumor potential in both hematologic and solid tumours, but the evidence does not support the application of BET inhibitors as a monotherapy for cancer treatment. Treatment-emergent toxicities such as thrombocytopenia and gastrointestinal disorders are also reported. Preclinical data suggest that BET inhibitors may have a promising future in combination with other anticancer agents.

Despite of various challenges, BET inhibitors have high potential in combinatorial therapy and the future development of next-generation inhibitors could be promising. Further studies are needed to determine the predictive biomarkers for therapeutic response, which would translate into the long-term success of BET inhibitors as personalized medicines in cancer treatment.
Histopathologic Spectrum of Findings Associated With Tattoos: Multicenter Study Series of 230 Cases
Authors: Portilla Maya Nataly , Kempf Werner , Perez Muñoz Noelia , Rodríguez-Martínez Paula , Posada Rodolfo , Fernández-Figueras María Teresa
Published: July 2021

Importance:

Reactions to tattoo may simulate common dermatosis or skin neoplasms. Histopathology allows diagnosis and helps determining the level and degree of inflammation associated, consequently orientating treatment.

Objective:

To describe the histological features found in biopsies of cutaneous reactions to tattoo.

Design:

This study was designed as a multicenter case series.

Setting:

All consecutive histopathological samples of tattoos referred from 1992 to 2019 to the Hospital General de Catalunya, Hospital Germans Trias i Pujol, and a private practice, all in Barcelona, Spain, and from the Kempf und Pfaltz Histologische Diagnostik in Zurich, Switzerland were retrieved from the files.

Participants and Exposure:

The inclusion criteria were all cosmetic/permanent makeup, artistic/professional, and traumatic tattoos associated with either inflammatory reactions alone and/or with tumors and/or infections. Exclusion criteria were cases without any associated pathologic finding in the place of the ink, amalgam tattoos, and medical or temporary tattoos.

Main Outcomes and Measures:

In all patients, clinical features (age, sex, location, tattoo color, and presentation) were recorded. Histological features evaluated included ink color, associated tumors or infections, and inflammatory reaction pattern. Inflammation was graded in low to moderate or severe.

Results:

From 477 biopsies diagnosed as tattoos, 230 cases from 226 patients met the inclusion criteria. Samples corresponded to 107 male and 120 female subjects and 3 of unknown gender. Median age was 39 years (ranging from 9 to 84 years). Fifty-three samples were referred from centers in Spain and 177 from the center in Switzerland. The series was analyzed in 2 parts: tattoos associated only with inflammatory reactions (117/230) and tattoos associated with tumors or infections (113/230). The most common form of inflammatory pattern associated with tattoo was the fibrosing reaction (79/117, 68%), followed by granulomatous reaction (56/117, 48%), lichenoid reaction (33/117, 28%), epithelial hyperplasia (28/117, 24%), pseudolymphoma (27/117, 23%) and spongiotic reaction (27/117, 23%). Combined features of 2 or more types of inflammatory patterns were seen in 64% cases.

Conclusions and Relevance:

Our series confirms that cutaneous reactions to tattoos are polymorphous. Inflammation tends to present with combined patterns. Infections are tending to decline, and pathologic findings are not specific to ink color or clinical features.
Comparison of Clinical, Ultrasound, and Electrophysiologic Changes in Chronic Inflammatory Demyelinating Polyneuropathy: A Prospective Study
Authors: Okhovat Ali Asghar , Nafissi Shahriar , Moradi Kamyar , Ziaadini Bentolhoda , Panahi Akram , Haghi Ashtiani Bahram , Fatehi Farzad
Published: July 2021

Purpose:

The follow-up and monitoring of response to immunomodulatory therapy in patients with chronic inflammatory demyelinating polyneuropathy are still challenging. Various outcome measures have been proposed in recent years, and some are now frequently used in daily clinical practice; however, reliable biomarkers for the disease activity and treatment response are lacking.

Methods:

Cross-sectional nerve area of the bilateral vagus, fifth and the sixth cervical spinal, median, ulnar, tibial, peroneal, and sural nerves were measured at 2 time points with an interval of 6 months using nerve ultrasound. The results were used to calculate the ultrasound pattern sumscore (UPSS). The correlation between UPSS change (ΔUPSS) and changes in functional and nerve conduction studies measures over the study period were assessed.

Results:

Sixteen patients completed this prospective, observational study. General linear model showed that ΔUPSS is significantly associated with ΔMedical Research Council sumscore (β = −0.72, P = 0.003), Δhandgrip strength (β = −0.57, P = 0.014), ΔRasch-built overall disability scale (β = −0.57, P = 0.010), and Δoverall neuropathy limitations scale (β = 0.75, P < 0.001), after adjustment of confounding variables. Nevertheless, ΔUPSS was not correlated with other clinical measures, including Δpinch power, Δ9-hole peg test, Δ10-m walking test, and Δnerve conduction study sumscore (P values > 0.05).

Conclusions:

Nerve ultrasound might be an efficient method for monitoring the functional status of patients with chronic inflammatory demyelinating polyneuropathy over time because the alterations in its scores could significantly reflect clinical changes.
Ostwald ripening in the presence of simultaneous occurrence of various mass transfer mechanisms: an extension of the Lifshitz–Slyozov theory
Authors: Alexandrova Irina V. , Alexandrov Dmitri V. , Makoveeva Eugenya V.
Published: July 2021

The Ostwald ripening stage of a phase transformation process with allowance for synchronous operation of various mass transfer mechanisms (volume diffusion and diffusion along the block boundaries and dislocations) and the initial condition for the particle-radius distribution function is theoretically studied. The initial condition is taken from the analytical solution describing the intermediate stage of a phase transition process. The present theory focuses on relaxation dynamics from the beginning of the ripening process to its final asymptotic state, which is described by the previously constructed theories (Slezov VV.et al.1978J. Phys. Chem. Solids39, 705–709. (doi:10.1016/0022-3697(78)90002-1) and Alexandrov & Alexandrova 2020Phil. Trans. R. Soc. A378, 20190247. (doi:10.1098/rsta.2019.0247)). An evolutionary behaviour of particle growth rates dependent on various mass transfer mechanisms and time is analytically described. The boundaries of the transition layer, which surround the blocking point, are found. The fundamental and relaxation contributions to the particle-radius distribution function are derived for the simultaneous occurrence of various mass transfer mechanisms. The left branch of this function is shifted to smaller particle radii whereas its right branch extends to the right of the blocking point as compared with the asymptotic universal distribution function. The theory under consideration well agrees with experimental data.

This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Evaporation kinetics of a polydisperse ensemble of drops
Authors: Ivanov Alexander A. , Alexandrova Irina V. , Alexandrov Dmitri V.
Published: July 2021

A mathematical model of the evaporation of a polydisperse ensemble of drops, with allowance for a nonlinear ‘diffusion’ term in the kinetic equation for the population density distribution function, is developed. The model describes the interaction of a gas phase with vaporizing drops: it has great potential for application in condensed matter physics, thermophysics and engineering devices (e.g. spray drying, cooling, power engineering). The kinetics of heat transfer between phases is theoretically studied. An analytical solution to the integro-differential equations of the process of droplet evaporation is found in a parametric form. Analytical solutions in the presence and absence of the ‘diffusion’ term are compared. It is shown that the fluctuations in particle evaporation rates (‘diffusion’ term in the Fokker–Planck equation) play a decisive role in the evolutionary behaviour of a polydisperse ensemble of vaporizing liquid drops.

This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Variable-order fractional master equation and clustering of particles: non-uniform lysosome distribution
Authors: Fedotov Sergei , Han Daniel , Zubarev Andrey Yu , Johnston Mark , Allan Victoria J.
Published: July 2021

In this paper, we formulate the space-dependent variable-order fractional master equation to model clustering of particles, organelles, inside living cells. We find its solution in the long-time limit describing non-uniform distribution due to a space-dependent fractional exponent. In the continuous space limit, the solution of this fractional master equation is found to be exactly the same as the space-dependent variable-order fractional diffusion equation. In addition, we show that the clustering of lysosomes, an essential organelle for healthy functioning of mammalian cells, exhibit space-dependent fractional exponents. Furthermore, we demonstrate that the non-uniform distribution of lysosomes in living cells is accurately described by the asymptotic solution of the space-dependent variable-order fractional master equation. Finally, Monte Carlo simulations of the fractional master equation validate our analytical solution.

This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Kinetics of solid–liquid interface motion in molecular dynamics and phase-field models: crystallization of chromium and silicon
Authors: Karim Eaman T. , He Miao , Salhoumi Ahmed , Zhigilei Leonid V. , Galenko Peter K.
Published: July 2021

The results of molecular dynamics (MD) simulations of the crystallization process in one-component materials and solid solution alloys reveal a complex temperature dependence of the velocity of the crystal–liquid interface featuring an increase up to a maximum at 10–30% undercooling below the equilibrium melting temperature followed by a gradual decrease of the velocity at deeper levels of undercooling. At the qualitative level, such non-monotonous behaviour of the crystallization front velocity is consistent with the diffusion-controlled crystallization process described by the Wilson–Frenkel model, where the almost linear increase of the interface velocity in the vicinity of melting temperature is defined by the growth of the thermodynamic driving force for the phase transformation, while the decrease in atomic mobility with further increase of the undercooling drives the velocity through the maximum and into a gradual decrease at lower temperatures. At the quantitative level, however, the diffusional model fails to describe the results of MD simulations in the whole range of temperatures with a single set of parameters for some of the model materials. The limited ability of the existing theoretical models to adequately describe the MD results is illustrated in the present work for two materials, chromium and silicon. It is also demonstrated that the MD results can be well described by the solution following from the hodograph equation, previously found from the kinetic phase-field model (kinetic PFM) in the sharp interface limit. The ability of the hodograph equation to describe the predictions of MD simulation in the whole range of temperatures is related to the introduction of slow (phase field) and fast (gradient flow) variables into the original kinetic PFM from which the hodograph equation is obtained. The slow phase-field variable is responsible for the description of data at small undercoolings and the fast gradient flow variable accounts for local non-equilibrium effects at high undercoolings. The introduction of these two types of variables makes the solution of the hodograph equation sufficiently flexible for a reliable description of all nonlinearities of the kinetic curves predicted in MD simulations of Cr and Si.

This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Nonlinear theory of macroscopic flow induced in a drop of ferrofluid
Authors: Zubarev Andrey Yu. , Chirikov Dmitry , Musikhin Anton , Raboisson-Michel Maxime , Verger-Dubois Gregory , Kuzhir Pavel
Published: July 2021

We present results of theoretical modelling of macroscopic circulating flow induced in a cloud of ferrofluid by an oscillating magnetic field. The cloud is placed in a cylindrical channel filled by a nonmagnetic liquid. The aim of this work is the development of a scientific basis for a progressive method of addressing drug delivery to thrombus clots in blood vessels with the help of the magnetically induced circulation flow. Our results show that the oscillating field can induce, inside and near the cloud, specific circulating flows with the velocity amplitude about several millimetres per second. These flows can significantly increase the rate of transport of the molecular non-magnetic impurity in the channel.

This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.