bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature, Pressure, Chemical Potential, and All That
Authors: Swendsen Robert H.
Published: February 2020

The Maxwell–Boltzmann distribution of momentum is obtained from statistical mechanics. Expressions for the temperature, pressure, and chemical potential are formulated as partial derivatives of the entropy with respect to energy, volume, and particle-number. The temperature scale is derived from comparison with the ideal gas law. The concept of the fundamental relation is defined as an expression that contains all thermodynamic information about the system of interest. Its differential form is introduced. Equations of state contain partial information about the thermal properties of a system and can be expressed as partial derivatives of the fundamental relation. The function of thermometers, pressure gauges, and thermal reservoirs are derived from these principles.
Extremum Principles
Authors: Swendsen Robert H.
Published: February 2020

This chapter derives the energy minimum principle from the entropy maximum principle. It postulates and consider the consequences of extensivity. From this are further derived minimum principles for the Helmholtz free energy, enthalpy, and Gibbs free energy. Because of its importance in engineering, exergy is also introduced, and the exergy minimum principle is justified. Analogously to these minimum principles, maximum principles can be derived for the Massieu functions from the entropy maximum principle. For the analysis of the entropy maximum principle, we isolated a composite system and released an internal constraint. Since the composite system was isolated, its total energy remained constant. The composite system went to the most probable macroscopic state after release of the internal constraint, and the total entropy went to its maximum.
Phase Transitions
Authors: Swendsen Robert H.
Published: February 2020

Phase transitions are introduced using the van der Waals gas as an example. The equations of state are derived from the Helmholtz free energy of the ideal gas. The behavior of this model is analyzed, and an instability leads to a liquid-gas phase transition. The Maxwell construction for the pressure at which a phase transition occurs is derived. The effect of phase transition on the Gibbs free energy and Helmholtz free energy is shown. Latent heat is defined, and the Clausius–Clapeyron equation is derived. Gibbs' phase rule is derived and illustrated.
Insulators and Semiconductors
Authors: Swendsen Robert H.
Published: February 2020

The origin of the strange band gaps that arise in the electron density of states in real materials is that the regular arrangement of the nuclei in a crystal lattice creates a periodic potential. This affects the energy levels of the electrons and gives rise to gaps in the energy spectrum. The properties of insulators and semiconductors are very important in modern technology. They are largely due to the Fermi–Dirac statistics obeyed by electrons. Following the discussion of the behavior of free electrons in the previous chapter, this one turns to the properties that emerge when electrons are subject to a periodic potential, as they are in a crystal. The periodic potential leads to Bloch's theorem, band theory, and the prediction of band gaps, which are responsible for the differences in the properties of metals, insulators, and semiconductors. Dopants and their basic effects are discussed.
Phase Transitions and the Ising Model
Authors: Swendsen Robert H.
Published: February 2020

Chapter 17 presented one example of a phase transition, the van der Waals gas. This chapter provides another, the Ising model, a widely studied model of phase transitions. We first give the solution for the Ising chain (one-dimensional model), including the introduction of the transfer matrix method. Higher dimensions are treated in the Mean Field Approximation (MFA), which is also extended to Landau theory. The Ising model is deceptively simple. It can be defined in a few words, but it displays astonishingly rich behavior. It originated as a model of ferromagnetism in which the magnetic moments were localized on lattice sites and had only two allowed values.
Thucydides’ History of the Peloponnesian War
Authors: Stewart Jon
Published: February 2020

Chapter 6 begins by introducing the reader to the Peloponnesian War and Thucydides’ history of it. An account is given of Thucydides’ explanation of his methodology and goal with his work. This is compared and contrasted to that of his predecessor Herodotus. Pericles’ Funeral Oration is discussed as a statement of the Athenian self-image in the context of war and empire. An account is given of Thucydides’ vivid description of the plague in Athens and how this eroded the political support for Pericles and thus ultimately led to the defeat of the city. Thucydides’ account of the Athenians’ negotiations with the Melians is given careful attention in relation to the issue of the use of power and international relations. While the Athenians effectively make a case for might-makes-right, the Melians appeal to a higher principle of justice. This sets the stage for a broader discussion of the nature of ethics. Careful attention is paid to Thucydides’ psychological and sociological observations about what happens when the fabric of society begins to break down in crisis situations.
Aristotle’s Politics
Authors: Stewart Jon
Published: February 2020

Chapter 8 begins with a basic introduction to Aristotle’s life and work. After a brief outline of the Politics, an account is given of Aristotle’s theory of the nature of human beings and their intimate connection to social and civic life. He claims that since humans are by nature political animals, the state should not be regarded as something artificial but rather as a product of nature itself. Along the same lines, Aristotle rather shockingly argues that slavery is a natural institution since there are fundamental differences in nature among human beings which separate them into categories of masters and slaves. Aristotle examines and weighs carefully the different forms of governmental organization that he is familiar with: democracy, oligarchy, and monarchy. He ultimately argues that each form of government on its own is problematic when it is employed exclusively. By contrast, the best government represents a balance, taking the best elements from each of the different forms of rule. The chapter ends with a consideration of Aristotle’s refutation of the split between nature and human law. It argues that law and regulation should not always be conceived as something unnatural that curbs our freedom and development. On the contrary, we can only develop by means of such restrictions.
The New Testament: Matthew
Authors: Stewart Jon
Published: February 2020

Chapter 11 explores the revolution in human thought that took place with the birth of Christianity. The chapter begins with a general account of the New Testament and its modern critics. A general introduction is also given to The Gospel of Matthew specifically, which is examined in order to outline the key elements in Jesus’ teachings. Jesus’ doctrine of love is contrasted to the Greco-Roman warrior ethic that has been discussed in connection with Homer and Virgil. It is argued that the Christian value system in effect inverts the previous value system of the pagan world by arguing that what is valuable in the world is in fact worthless. By contrast, Jesus points to the inner sphere of the individual. This also marks a shift in the Jewish tradition, which was focused on the obedience to external law. This can be seen most clearly in Jesus’ ethical teachings when he claims that the locus of sin is not in the act in the external world but rather in the heart of the individual. This is the beginning of an important change in thinking about the nature of responsibility. Christianity contributed in an important way to the development of subjectivity and inwardness. The chapter ends with a consideration of certain elements of Christianity in the thought of Kierkegaard and Nietzsche.
The Death of the French Atlantic
Authors: Forrest Alan
Published: February 2020

The Preface places the book in its historiographical context and asks how far the French Atlantic did ‘die’ in the Age of Revolutions. It places the crisis of the late eighteenth century in a transnational context, linking the histories of France and the Caribbean and discussing fortunes of port cities like Nantes, Bordeaux, and La Rochelle in a deliberately comparative manner. The book draws heavily on recent work on slavery, the slave trade, and the public memory of slavery that has been so influential on both sides of the Atlantic, and sets out to explain political and moral forces, as well as the purely economic issues, which combined to threaten French colonial prosperity.
The Years of Economic Prosperity
Authors: Forrest Alan
Published: February 2020

This chapter examines the prosperity of the Atlantic port cities across the eighteenth century—their so-called ‘golden age’—and the rise to prominence of great merchant houses and trading firms, with a discussion of the degree to which they became dependent on Atlantic shipping for their profits. It shows how merchant families rose to positions of social prominence and distinction, and shows how nobles, too, from Brittany and the Atlantic region came to invest in colonial shipping. But the century was not a period of unbroken prosperity. War frequently intervened, leading to the disruption of the shipping lanes and the loss or capture of French vessels by enemy ships. It also drove many French merchants to privateering, which was a customary and longstanding response in times of war.
The Illegal Slave Trade
Authors: Forrest Alan
Published: February 2020

The Congress of Vienna did not end the slave trade in French ports, nor across the North Atlantic, and the return of peace restricted the activities of naval vessels in boarding and arresting suspect vessels. Nantes merchants, in particular, were eager to return to slaving and dreamed of the return of pre-revolutionary prosperity. But the French government showed less tolerance of slaving and took an increasingly active part in policing the trade. The chapter discusses the extent of French illegal slaving under the Restoration and the increased dangers it faced, following vessels from Nantes and Bordeaux on illegal voyages to the African coast, noting the higher risks of death and disease, and discussing the various ruses adopted to avoid the attention of the authorities.
Conclusion
Authors: Forrest Alan
Published: February 2020

The conclusion looks at the long-term damage done to the economy of France’s Atlantic ports by the crisis of the Age of Revolutions, and discusses the different ways in which they sought to restore their fortunes. It returns to the central question posed at the beginning of the book: which of the threats they faced in war and revolution proved the most damaging? Over more than twenty years of war, the disruption suffered was on a scale unparalleled during the wars of the eighteenth century. But wars end, and periods of peace follow when overseas commerce can again flourish. Revolution, allied to an anti-slavery campaign, inflicted lasting damage rather than temporary disruption, and made it impossible for the Atlantic ports to return to their established ways.
A False Tree of Liberty
Authors: Marks Susan
Published: February 2020

This book is concerned with the history of the idea of human rights. It puts aside familiar questions such as ‘Where do human rights come from?’ and ‘When did human rights begin?’, for the sake of looking into connections between debates about the rights of man and developments within the history of capitalism. The focus is on England, where, at the end of the eighteenth century, a heated controversy over the rights of man coincided with the final enclosure of common lands and the momentous changes associated with early industrialisation. Tracking back still further to sixteenth- and seventeenth-century writing about dispossession, resistance and rights, the book reveals a forgotten tradition of thought about central issues in human rights, with implications for their prospects in the world today.
Two Early Modern Revolts
Authors: Marks Susan
Published: February 2020

This chapter continues the discussion of early English social criticism with a consideration of two uprisings of the early modern period: Kett’s Rebellion (1549) and the Midland Rising (1607). These uprisings were formidable instances of organised resistance to enclosure and related changes, and the texts which have come down to us concerning them connect that resistance to a belief in the original equality of all human beings, the common humanity of rich and poor, and the fundamental right of everyone to live (including the right to buy essential provisions at a fair and affordable price).
In the Shadow of Dearth
Authors: Marks Susan
Published: February 2020

Mid-1790s England saw an episode of fearful dearth. This chapter continues discussion of the contested meaning of the rights of man in the Revolution Controversy, in the light of approaches to dearth which emphasised, on the one hand, the moral economy of the poor and, on the other hand and alternatively, the new ‘political economy’ of laissez faire. It transpires that, for Thomas Paine and other proponents of the rights of man such as John Thelwall, the rights of the living were not simply a matter of political control and popular sovereignty. The living also had the right to live.
Improvement and the Real Rights of Man
Authors: Marks Susan
Published: February 2020

In completing the book’s discussion of the contested significance of the rights of man in the Revolution controversy, this chapter directs attention to contemporaneous developments affecting land. Thanks to the process of Parliamentary enclosure, the second half of the eighteenth century saw the privatisation of virtually all remaining common land in England. What did it mean, in that context, to assert the right to live? The most influential account emphasised welfare and wages. In contrast, Thomas Spence put forward an alternative vision in which the focus was on the social-structural conditions in which security of subsistence could be achieved.
Before Bluegrass (1920s–1946)
Authors: Lornell Kip
Published: February 2020

This chapter focuses on the country music scene prior to the development of bluegrass. Much of this discussion describes early radio performances, the scattered newspaper accounts of this music, and the few commercial phonograph records made during this period. A few important hillbilly musicians like Jimmie Rodgers and the Hill Billies performed in the District in the 1920s and 1930s. The Stoneman Family and their music exemplify both the migration into Washington, DC, and the music they brought with them. Like many others who moved to the District and nearby suburbs during the first fifty years of the 20th century, most of them came from Virginia or the Carolinas. Most of them also brought their musical interests with them.
Prelude: Sounding Social Identity
Authors: Seeman Sonia Tamar
Published: February 2020

Opening with a description of a Roman oyun havası (Roman dance tune), this chapter describes the gestures, movements, and self-identifying references that this genre evokes. While European, Ottoman and Turkish literature seem to have a rich body of information regarding “Gypsies,” those representations are largely presented in the absence of actual Romani voices. Given the historical experiences of social exclusion political marginalization and discrimination by Turkish Roman, the struggle for control over self-naming was also channeled through and refined in the ongoing creation of their own narratives in commodified and mass-mediated Roman oyun havası. The philosophical concepts of iconicity, metaphoricity, and mimesis as applied to Roman oyun havası suggest one means for examining the dynamic relationship between cultural practices, performances, and their social effects. This chapter also discusses issues of representation in historiographic research, provides an outline of the book and chapter topics, and describes the author’s field work and positionality.
Inscribing çingene in Late Ottoman Cultural Forms
Authors: Seeman Sonia Tamar
Published: February 2020

This chapter focuses on the relationship between Ottoman social order and urban popular culture. Social upheavals contributed to the intensified display of the çingene stereotype, with the çingene representing the experience of social marginalization. Playing out the anxieties of urban audiences as they confronted problems of modernity, urbanism, social disruption, and moral decay, the stereotypical figure of the çingene remained consistent from the late nineteenth century to the 1990s. A discussion of the dramatic nineteenth century Tanzimat reforms is followed by analyses of çingene characters in karagöz shadow puppetry, kanto theatrical songs, and Ottoman literature. The çingene was portrayed in two irreconcilable types: as an essentialized, nomad in pastoral rural settings; as the polluted degenerate and potentially contagious agent of urban chaos, social disorder, and moral decadence. By portraying the “çingene” as the quintessential “other” among an array of diverse social types, these forms rendered the anxiety-producing urban social landscape in stark relief.
From çingene Accompanist to Instrumental Soloist
Authors: Seeman Sonia Tamar
Published: February 2020

Alongside state discourses of canonical Turkish music, local commercial recording companies relied on the innovative skills of Romani instrumentalists who could generate a variety of urban dance tunes for the burgeoning record market. By conferring the prestige of nightclub music on these instrumental compositions, these new Romani instrumental stars opened up a musical space for hearing negative “çingene” identity as prestigious “Roman.” Biographies of artists Haydar Tatlıyay, Şükrü Tunar, Kadri Şençalar, and Mustafa Kandıralı focus on their mediation of community-based music-making with nightclub and state radio styles. This chapter presents musical analysis of the link between keriz and the structuring of oyun havası in the first mass-produced recorded presentation of the social term, “Roman” by Yılmaz Şanlıel and Nazif Girgin. By introducing the group name “Roman” and “Romen” as a musical label for keriz-based instrumental dance music, these artists founded a genre and stylistic space for incremental revisions of social self-representation.
New Methods for the Cross-Section of Returns
Authors: Karolyi G Andrew , Van Nieuwerburgh Stijn
Published: February 2020

The cross-section and time series of stock returns contains a wealth of information about the stochastic discount factor (SDF), the object that links cash flows to prices. A large empirical literature has uncovered many candidate factors—many more than seem plausible—to summarize the SDF. This special volume of the Review of Financial Studies presents recent advances in extracting information from both the cross-section and the time series, in dealing with issues of replication and false discoveries, and in applying innovative machine-learning techniques to identify the most relevant asset pricing factors. Our editorial summarizes what we learn and offers a few suggestions to guide future work in this exciting new era of big data and empirical asset pricing.
Examining the Progressive Behavior and Neuropathological Outcomes Associated with Chronic Repetitive Mild Traumatic Brain Injury in Rats
Authors: Eyolfson Eric , Yamakawa Glenn R , Griep Yannick , Collins Reid , Carr Thomas , Wang Melinda , Lohman Alexander W , Mychasiuk Richelle
Published: February 2020

While the physical and behavioral symptomologies associated with a single mild traumatic brain injury (mTBI) are typically transient, repetitive mTBIs (RmTBI) have been associated with persisting neurological deficits. Therefore, this study examined the progressive changes in behavior and the neuropathological outcomes associated with chronic RmTBI through adolescence and adulthood in male and female Sprague Dawley rats. Rats experienced 2 mTBIs/week for 15 weeks and were periodically tested for changes in motor behavior, cognitive function, emotional disturbances, and aggression. Brain tissue was examined for neuropathological changes in ventricle size and presentation of Iba1 and GFAP. We did not see progressively worse behavioral impairments with the accumulation of injuries or time, but did find evidence for neurological and functional change (motor disturbance, reduced exploration, reduced aggression, alteration in depressive-like behavior, deficits in short-term working memory). Neuropathological assessment of RmTBI animals identified an increase in ventricle size, prolonged changes in GFAP, and sex differences in Iba1, in the corpus callosum, thalamus, and medial prefrontal cortex. Telomere length reduced exponentially as the injury load increased. Overall, chronic RmTBI did not result in accumulating behavioral impairment, and there is a need to further investigate progressive behavioral changes associated with repeated injuries in adolescence and young adulthood.
Spindle Orientation-Independent Control of Cell Fate Determination by RGS3 and KIF20A
Authors: Qiu Runxiang , Murai Kiyohito , Lu Qiang
Published: February 2020

It was proposed that similar to its role in the invertebrate nervous system, mitotic spindle orientation (or cell cleavage plane orientation) of a dividing neural progenitor cell specifies the fate of daughter cells in the mammalian brain, modulating the production of neurons via symmetric versus asymmetric cell divisions during the course of neurogenesis. Experimental tests of the sufficiency of spindle/cleavage plane orientation in mammalian cell fate determination have yielded conflicting results. On the other hand, the necessity of spindle/cleavage plane orientation in mammalian cell fate determination has not yet been addressed. Here we examined the necessity of spindle/cleavage plane orientation during cortical neurogenesis in mice with loss-of-function of the RGS3-KIF20A interaction axis. We present evidence that while inactivation of RGS3 or KIF20A was linked to a shift in neural progenitor cells from proliferative to differentiative divisions in the developing cortex, these genetic mutations did not lead to anticipated alteration in the orientation of spindle/cleavage plane. Our results indicate that the RGS3-KIF20A axis regulates the balance between proliferation and differentiation in the mammalian cortex employing a mechanism independent of spindle/cleavage plane orientation. These data also caution against using spindle/cleavage plane orientation as the synonym for cell fate determination.
Blautia faecicola sp. nov., isolated from faeces from a healthy human
Authors: Kim Ji-Sun , Park Jam-Eon , Lee Keun Chul , Choi Seung-Hyeon , Oh Byeong Seob , Yu Seung Yeob , Eom Mi Kyung , Kang Se Won , Han Kook-Il , Suh Min Kuk , Lee Dong Ho , Yoon Hyuk , Kim Byung-Yong , Yang Seung-Jo , Lee Ju Huck , Lee Jung-Sook , Park Seung-Hwan
Published: February 2020

An obligately anaerobic, Gram-stain-positive, non-motile and coccoid- or oval-shaped bacterium, designated strain KGMB01111T, was isolated from faeces from a healthy Korean. Comparative analysis of 16S rRNA gene sequences indicated that KGMB01111T was closely related to Ruminococcus gauveauii CCRI-16110T (93.9 %) and

Blautia stercoris

GAM6-1T (93.7 %), followed by

Clostridium nexile

DSM 1787T (93.5 %),

Blautia producta

ATCC 27340T (93.4 %),

Blautia hydrogenotrophica

DSM 10507T (93.1 %) and

Blautia coccoides

ATCC 29236T (93.1 %) within the family

Lachnospiraceae

(

Clostridium

rRNA cluster XIVa). Phylogenetic analysis based on the 16S rRNA gene sequences indicated that KGMB01111T formed a separate branch with species in the genus

Blautia

. The major cellular fatty acids (>10.0 %) were C16 : 0 and C18 : 1
cis 9 dimethyl acetal (DMA), and the major polar lipids were aminophospholipids and lipids. KGMB01111T contained meso-diaminopimelic acid in cell-wall peptidoglycan. The predominant end product of fermentation produced by KGMB01111T was acetic acid. Based on the whole-genome sequence, the DNA G+C content of the isolate was 44.7 mol%. On the basis of the phenotypic, chemotaxonomic and phylogenetic characteristics, KGMB01111T represents a novel species within the genus

Blautia

for which the name Blautia faecicola sp. nov. is proposed. The type strain is KGMB01111T (=KCTC 15706T=DSM 107827T).
Pectobacterium parvum sp. nov., having a Salmonella SPI-1-like Type III secretion system and low virulence
Authors: Pasanen Miia , Waleron Malgorzata , Schott Thomas , Cleenwerck Ilse , Misztak Agnieszka , Waleron Krzysztof , Pritchard Leighton , Bakr Ramadan , Degefu Yeshitila , van der Wolf Jan , Vandamme Peter , Pirhonen Minna
Published: February 2020

Pectobacterium

strains isolated from potato stems in Finland, Poland and the Netherlands were subjected to polyphasic analyses to characterize their genomic and phenotypic features. Phylogenetic analysis based on 382 core proteins showed that the isolates clustered closest to

Pectobacterium polaris

but could be divided into two clades. Average nucleotide identity (ANI) analysis revealed that the isolates in one of the clades included the

P. polaris

type strain, whereas the second clade was at the border of the species

P. polaris

with a 96 % ANI value. In silico genome-to-genome comparisons between the isolates revealed values below 70%, patristic distances based on 1294 core proteins were at the level observed between closely related

Pectobacterium

species, and the two groups of bacteria differed in genome size, G+C content and results of amplified fragment length polymorphism and Biolog analyses. Comparisons between the genomes revealed that the isolates of the atypical group contained SPI-1-type Type III secretion island and genes coding for proteins known for toxic effects on nematodes or insects, and lacked many genes coding for previously characterized virulence determinants affecting rotting of plant tissue by soft rot bacteria. Furthermore, the atypical isolates could be differentiated from

P. polaris

by their low virulence, production of antibacterial metabolites and a citrate-negative phenotype. Based on the results of a polyphasic approach including genome-to-genome comparisons, biochemical and virulence assays, presented in this report, we propose delineation of the atypical isolates as a novel species Pectobacterium parvum, for which the isolate s0421T (CFBP 8630T=LMG 30828T) is suggested as a type strain.
Genomic characterization of the non-O1/non-O139 Vibrio cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018
Authors: Arteaga Mónica , Velasco Juliana , Rodriguez Shelly , Vidal Maricel , Arellano Carolina , Silva Francisco , Carreño Leandro J. , Vidal Roberto , Montero David A.
Published: February 2020

Vibrio cholerae

is a human pathogen, which is transmitted by the consumption of contaminated food or water.

V. cholerae

strains belonging to the serogroups O1 and O139 can cause cholera outbreaks and epidemics, a severe life-threatening diarrheal disease. In contrast, serogroups other than O1 and O139, denominated as non-O1/non-O139, have been mainly associated with sporadic cases of moderate or mild diarrhea, bacteremia and wound infections. Here we investigated the virulence determinants and phylogenetic origin of a non-O1/non-O139

V. cholerae

strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018. We found that this outbreak strain lacks the classical virulence genes harboured by O1 and O139 strains, including the cholera toxin (CT) and the toxin-coregulated pilus (TCP). However, this strain carries genomic islands (GIs) encoding Type III and Type VI secretion systems (T3SS/T6SS) and antibiotic resistance genes. Moreover, we found these GIs are wide distributed among several lineages of non-O1/non-O139 strains. Our results suggest that the acquisition of these GIs may enhance the virulence of non-O1/non-O139 strains that lack the CT and TCP-encoding genes. Our results highlight the pathogenic potential of these

V. cholerae

strains.
Aberrant pathogenic GM-CSF+T cells and inflammatory CD14+CD16+monocytes in severe pulmonary syndrome patients of a new coronavirus
Authors: Zhou Yonggang , Fu Binqing , Zheng Xiaohu , Wang Dongsheng , Zhao Changcheng , qi Yingjie , Sun Rui , Tian Zhigang , Xu Xiaoling , Wei Haiming
Published: February 2020

Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality1,2. Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus was reported at December 2019 (2019-nCoV) in the city Wuhan, Hubei province, China3–5, which was also named as pneumonia-associated respiratory syndrome (PARS)6. Up to 9th of February 2020, at least 37, 251 cases have been reported with 812 fatal cases according to the report from China CDC. However, the immune mechanism that potential orchestrated acute mortality from patients of 2019-nCoV is still unknown. Here we show that after the 2019-nCoV infection, CD4+T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc. The cytokines environment induces inflammatory CD14+CD16+monocytes with high expression of IL-6 and accelerates the inflammation. These aberrant and excessive immune cells may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality. Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology. Therefore, we suggest that monoclonal antibody that targets the GM-CSF or interleukin 6 receptor may potentially curb immunopathology caused by 2019-nCoV and consequently win more time for virus clearance.
Candidate targets for immune responses to 2019-Novel Coronavirus (nCoV): sequence homology- and bioinformatic-based predictions
Authors: Grifoni Alba , Sidney John , Zhang Yun , Scheuermann Richard H , Peters Bjoern , Sette Alessandro
Published: February 2020

Effective countermeasures against the recent emergence and rapid expansion of the 2019-Novel Coronavirus (2019-nCoV) require the development of data and tools to understand and monitor viral spread and immune responses. However, little information about the targets of immune responses to 2019-nCoV is available. We used the Immune Epitope Database and Analysis Resource (IEDB) resource to catalog available data related to other coronaviruses, including SARS-CoV, which has high sequence similarity to 2019-nCoV, and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in 2019-nCoV that have high homology to SARS virus. Parallel bionformatic predictions identifieda prioripotential B and T cell epitopes for 2019-nCoV. The independent identification of the same regions using two approaches reflects the high probability that these regions are targets for immune recognition of 2019-nCoV.

ONE SENTENCE SUMMARY

We identified potential targets for immune responses to 2019-nCoV and provide essential information for understanding human immune responses to this virus and evaluation of diagnostic and vaccine candidates.
Application of n-of-1 clinical trials in personalized nutrition research: a trial protocol for Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR)
Authors: Tian Yunyi , Ma Yue , Fu Yuanqing , Zheng Ju-Sheng
Published: February 2020

Personalized dietary recommendations can help with more effective disease prevention. This study aims to investigate the individual postprandial glucose response to diets with diverse macronutrient proportions at both individual level and population level and explore the potential of the novel single-patient (n-of-1) trial for the personalization of diet. Secondary outcomes include individual phenotypic response and the effects of dietary ingredients on the composition and structure of gut microbiota. Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR) is a multiple crossover feeding trial consisting of three successive 12-day dietary intervention pairs including a 6-day wash-out period before each 6-day isocaloric dietary intervention (a 6-day high-fat, low-carbohydrate (HF-LC) diet and a 6-day low-fat, high-carbohydrate (LF-HC) diet). The results will help provide personalized dietary recommendation on macronutrients in terms of postprandial blood glucose response. Well-designed n-of-1 trial is likely to become an effective method of optimizing individual health and advancing health care. This trial is registered at clinicaltrials.gov (NCT04125602).
Short-term versus 6-week prednisone in the treatment of subacute thyroiditis: a randomized controlled trial
Authors: Duan Lian , Feng Xiaoli , Zhang Rui , Tan Xiaojuan , Xiang Xiaoyan , Shen Rufei , Zheng Hongting
Published: February 2020

Background

Moderate-to-severe subacute thyroiditis is commonly treated with 6-8 weeks glucocorticoids; however, no studies have described short-term prednisone treatment for subacute thyroiditis. We evaluated the efficacy of this treatment for subacute thyroiditis.

Methods

This was a 24-week, prospective, single-blind, randomized controlled study. Patients aged 18-70 years with subacute thyroiditis were hospitalized from August 2013 to December 2014. Patients with moderate-to-severe symptoms were randomized to receive either 30 mg/d prednisone for 1 week and then switched to 1 week of nonsteroidal anti-inflammatory drugs or 6 weeks of prednisone. The primary endpoints were the differences in efficacy at the end of treatment between two groups. Secondary endpoints included differences between the two groups in parameters of side effects at withdrawal and thyroid function at weeks 6, 12, 24.

Results

Of 96 patients screened, 52 subjects were randomized and 50 completed the study. Efficacy and recurrence rates were not significantly different at withdrawal in both groups (P=0.65). Parathyroid hormone (28.8 vs 38.9 pg/ml, p=0.011) and mean systolic blood pressure (113.9 vs 122.4 mmHg, p=0.023) were significantly lower in the experimental group than in the control group at discontinuation. No significant differences were observed in other secondary endpoints at withdrawal and in thyroid function at the 6th, 12th and 24th week during the follow-up time between the two groups.

Conclusions

Fewer side effects of glucocorticoids and similar efficacy and recurrence rates were observed with short-term prednisone compared with those with 6-week treatment for subacute thyroiditis. Short-term prednisone with a better safety profile may be as one alternative strategy for ameliorating moderate-to-severe symptoms of subacute thyroiditis.

Trial registration

Trial registration number NCT01837433. Registered with Clinicaltrials.gov on 23 April 2013
Refractive errors, ocular biometry and diabetic retinopathy: a systematic review
Authors: He Miao , Chen Haiying , Wang Wei
Published: February 2020

Diabetic retinopathy (DR) is one of the major causes of visual impairment and blindness worldwide. The onset and progression of DR are influenced by systemic factors such as hyperglycemia and hypertension as well as ocular parameters. A better knowledge of the risk factors for DR is vital to improving the outcome of patients with DR and risk stratification. More recently, there has been increasing focus on the influence of myopia on DR development. Some observational studies have reported myopia being a protective factor for the development of DR, however the findings were inconsistent. In addition, it remains unclear whether it was myopia, axial length (AL), or other refractive factors that play the protective role. The protective mechanism against DR may be related to ocular elongation, posterior vitreous detachment, low perfusion in the retina and the abnormal cytokine profile. This systematic review will summarize the association of DR with refractory status as well as different refractive components including anterior chamber depth, refractory power of the lens, AL, and axial length-to-corneal radius ratio.
Estimating number of global importations of COVID-19 from Wuhan, risk of transmission outside mainland China and COVID-19 introduction index between countries outside mainland China
Authors: Sun Haoyang , Dickens Borame L , Chen Mark I. C. , Cook Alex R , Clapham Hannah E
Published: February 2020

Background

The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China in early December 2019 has caused widespread transmission within the country, with over 1,000 deaths reported to date. Other countries have since reported coronavirus disease 2019 (COVID-19) importation from China, with some experiencing local transmission and even case importation from countries outside China. We aim to estimate the number of cases imported from Wuhan to each country or territory outside mainland China, and with these estimates assess the risk of onward local transmission and the relative potential of case importation between countries outside China.

Methods

We used the reported number of cases imported from Wuhan and flight data to generate an uncertainty distribution for the estimated number of imported cases from Wuhan to each location outside mainland China. This uncertainty was propagated to quantify the local outbreak risk using a branching process model. A COVID-19 introduction index was derived for each pair of donor and recipient countries, accounting for the local outbreak risk in the donor country and the between- country connectivity.

Results

We identified 13 countries or territories outside mainland China that may have under-detected COVID-19 importation from Wuhan, such as Thailand and Indonesia. In addition, 16 countries had a local outbreak risk estimate exceeding 50%, including four outside Asia. The COVID-19 introduction index highlights potential locations outside mainland China from which cases may be imported to each recipient country.

Conclusions

As SARS-CoV-2 continues to spread globally, more epicentres may emerge outside China. Hence, it is important for countries to remain alert for the possibilities of viral introduction from other countries outside China, even before local transmission in a source country becomes known.
Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019
Authors: Liu Yanli , Sun Wenwu , Li Jia , Chen Liangkai , Wang Yujun , Zhang Lijuan , Yu Li
Published: February 2020

Background

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a cluster of coronavirus disease 2019 (COVID-19). We reported the clinical characteristics of COVID-19 patients with acute respiratory distress syndrome (ARDS), and further investigated the treatment and progression of ARDS in COVID-19.

Methods

This study enrolled 109 patients with COVID-19 admitted to the Central Hospital of Wuhan, a designated hospital in Wuhan, China, from January 2 to February 1, 2020. Patients were followed up to February 12, 2020. The clinical data were collected from the electronic medical records. The differences in the treatment and progression with the time and the severity of ARDS were determined.

Findings

Among 109 patients, mean age was 55 years, and 59 patients were male. With a median 15 days (range, 4 to 30 days) follow-up period, 31 patients (28.4%) died, while 78 (71.6%) survived and discharged. Of all patients, 53 (48.6%) developed ARDS. Compared to non-ARDS patients, ARDS patients were elder (mean age, 61 years vs. 49 years), and more likely to have the coexistent conditions, including diabetes (20.8% vs. 1.8%), cerebrovascular disease (11.3% vs. 0%), and chronic kidney disease (15.1% vs. 3.6%). Compared to mild ARDS patients, those with moderate and severe ARDS had higher mortality rates. No significant effect of antivirus, glucocorticoid, or immunoglobulin treatment on survival was observed in patients with ARDS.

Interpretation

The mortality rate increased with the severity of ARDS in COVID-19, and the effects of current therapies on the survival for these patients were not satisfactory, which needs more attention from clinicians.

Funding

Health and Family Planning Commission of Wuhan Municipality.
Integratedin silicoand 3Din vitromodel of macrophage migration in response to physical and chemical factors in the tumor microenvironment
Authors: Lee Sharon Wei Ling , Seager R.J. , Litvak Felix , Spill Fabian , Sieow Je Lin , Penny Hweixian Leong , Kumar Dillip , Tan Alrina Shin Min , Wong Siew Cheng , Adriani Giulia , Zaman Muhammad H , Kamm Roger Dale
Published: February 2020

Macrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored the biochemical mechanisms that drive pro-tumor macrophage functions, however the role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with tumor cells and macrophages to study how IF affects macrophage migration and its potential contribution to cancer invasion. The presence of either tumor cells or IF individually increased macrophage migration directedness and speed. Interestingly, there was no additive effect on macrophage migration directedness and speed under the simultaneous presence of tumor cells and IF. Further, we present anin silicomodel that couples chemokine-mediated signaling with mechanosensing networks to explain ourin vitroobservations. The model proposes IL-8, CCL2 and β-integrin as key pathways that commonly regulate various Rho GTPases. In agreement,in vitromacrophage migration remained elevated when exposed to a saturating concentration of recombinant IL-8 or CCL2, or to the co-addition of a sub-optimal concentration of both cytokines. Moreover, antibody blockade against IL-8 and/or CCL2 inhibited migration that could be restored by IF, indicating cytokine-independent mechanisms of migration induction. Importantly, we demonstrate the utility of an integratedin silicoand 3Din vitroapproach to aid the design of tumor-associated macrophage-based immunotherapeutic strategies.
Elongation Index as a Sensitive Measure of Cell Deformation in High-Throughput Microfluidic Systems
Authors: Hymel S. J. , Lan H. , Khismatullin D. B.
Published: February 2020

Abstract

One of the promising approaches for high-throughput screening of cell mechanotype is microfluidic deformability cytometry (mDC) in which the apparent deformation index (DI) of the cells stretched by extensional flow at the stagnation point of a cross-slot microchannel is measured. The DI is subject to substantial measurement errors due to cell offset from the flow centerline and velocity fluctuations in inlet channels, leading to artificial widening of DI vs. cell size plots. Here, we simulated an mDC experiment using a custom computational algorithm for viscoelastic cell migration. Cell motion and deformation in a cross-slot channel was modeled for fixed or randomized values of cellular mechanical properties (diameter, shear elasticity, cortical tension) and initial cell placement, with or without sinusoidal fluctuations between the inlet velocities. Our numerical simulation indicates that mDC loses sensitivity to changes in shear elasticity when the offset distance exceeds 5 μm, and just 1% velocity fluctuation causes an 11.7% drop in the DI. The obtained relationships between the cell diameter, shear elasticity, and offset distance were used to establish a new measure of cell deformation, referred to as “Elongation Index” (EI). In the randomized study, the EI scatter plots were visibly separated for the low and high elasticity populations of cells, with a mean of 300 and 3,500 Pa, while the standard DI output was unable to distinguish between these two groups of cells. The successful suppression of the offset artefacts with a narrower data distribution was shown for the EI output of MCF-7 cells.

Statement ofSignificance

This study establishes a new measure of high-throughput microfluidic deformability cytometry, referred to as “elongation index”, that is not subject to cell offset artefacts and can sensibly and reliably detect disease-induced changes in mechanical properties of living cells.
Genetic, Cellular, and Connectomic Characterization of the Adult Human Brain Regions Commonly Plagued by Glioma
Authors: Mandal Ayan S. , Romero-Garcia Rafael , Hart Michael G. , Suckling John
Published: February 2020

A better understanding of the nonrandom localization patterns of gliomas across the brain could lend clues to the origins of these types of tumors. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combined neuroimaging data from 335 adult patients with high- and low-grade glioma to form a replicable tumor frequency map. Using this map, we demonstrated that glioma frequency is elevated in association cortex and correlated with multiple graph-theoretical metrics of high functional connectedness. Brain regions populated with stem-like cells also exhibited a high glioma frequency. Furthermore, gliomas were localized to brain regions enriched with the expression of genes associated with chromatin organization and synaptic signaling. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently influence the anatomic localization of oncogenesis.
A novel cortical biomarker signature for predicting pain sensitivity: protocol for the PREDICT longitudinal analytical validation study
Authors: Seminowicz David A , Bilska Katarzyna , Chowdhury Nahian S , Skippen Patrick , Millard Samantha K , Chiang Alan KI , Chen Shuo , Furman Andrew J , Schabrun Siobhan M
Published: February 2020

Introduction

Temporomandibular disorder (TMD) is a common musculoskeletal pain condition with development of chronic symptoms in 49% of patients. Although a number of biological factors have shown an association with chronic TMD in cross-sectional and case control studies, there are currently no biomarkers that can predict the development of chronic symptoms. The PREDICT study aims to undertake analytical validation of a novel peak alpha frequency (PAF) and corticomotor excitability (CME) biomarker signature using a human model of the transition to sustained myofascial temporomandibular pain (masseter intramuscular injection of nerve growth factor [NGF]). This paper describes, a-priori, the methods and analysis plan.

Methods and analysis

This study uses a multi-site longitudinal, experimental study to follow individuals for a period of 30 days as they progressively develop and experience complete resolution of NGF-induced muscle pain. 150 healthy participants will be recruited. Participants will complete twice daily electronic pain dairies from Day 0 to Day 30 and undergo assessment of pressure pain thresholds, and recording of PAF and CME on Days 0, 2 and 5. Intramuscular injection of NGF will be given into the right masseter muscle on Days 0 and 2. The primary outcome is pain sensitivity.

Ethics and dissemination

Ethical approval has been obtained from The University of New South Wales (HC190206) and the University of Maryland Baltimore (HP-00085371). Dissemination will occur through presentations at National and International conferences and publications in international peer-reviewed journals.

Registration details

ClinicalTrials.gov: NCT04241562 (prospective)

STRENGTHS AND LIMITATIONS OF THIS STUDY

PREDICT is the first study to undertake analytical validation of a peak alpha frequency and corticomotor excitability biomarker signature. The study will determine the sensitivity, specificity and accuracy of this biomarker signature at predicting pain sensitivity.

PREDICT will establish the reportable range of test results and determine automation and simplification of methods for biomarker detection in the clinic.

The methods and statistical analysis plan are pre-specified to ensure reporting transparency.

Future patient studies will be required for clinical validation.