bluuebunny/crossref_metadata_2025 huggingface dataset:
Charles Dickens and the Properties of Fiction
Authors: Dasgupta Ushashi
Published: June 2020

This book explores the significance of rental culture in Charles Dickens’s fiction and journalism. It reveals tenancy, or the leasing of real estate in exchange for money, to be a governing force in everyday life in the nineteenth century. It casts a light into back attics and landladies’ parlours, and follows a host of characters—from slum landlords exploiting their tenants, to pairs of friends deciding to live together and share the rent. In this period, tenancy shaped individuals, structured communities, and fascinated writers. The vast majority of London’s population had an immediate economic relationship with the houses and rooms they inhabited, and Dickens was highly attuned to the social, psychological, and imaginative corollaries of this phenomenon. He may have been read as an overwhelming proponent of middle-class domestic ideology, but if we look closely, we see that his fictional universe is a dense network of rented spaces. He is comfortable in what he calls the ‘lodger world’, and he locates versions of home in a multitude of unlikely places. These are not mere settings, waiting to be recreated faithfully; rented space does not simply provide a backdrop for incident in the nineteenth-century novel. Instead, it plays an important part in influencing what takes place. For Dickens, to write about tenancy can often mean to write about writing—character, authorship, and literary collaboration. More than anything, he celebrates the fact that unassuming houses brim with narrative potential: comedies, romances, mysteries, and comings-of-age take place behind their doors.
How to Live Together
Authors: Dasgupta Ushashi
Published: June 2020

This chapter discusses Dickens’s late career, reading the multi-authored Christmas numbers of Household Words and All the Year Round alongside Little Dorrit, Our Mutual Friend, The Mystery of Edwin Drood, and novels by Marmion Savage and WM Thackeray. For Dickens, Christmas is an opportunity to clarify and problematize definitions of ‘home’ and ‘family’. He compares three modes of dwelling: living alone in chambers, living with another person, and lodging. While chambers generate a particular kind of urban loneliness, Dickens suggests that sharing accommodation with a friend consolidates homosocial and homoerotic ties, turning rented space into queer space. Many of the Christmas numbers are set in rented spaces, and contemplate the joys and trials of cohabitation. These collections suggest that the dynamics of the lodging house capture the politics of Dickens’s circle. Here, Dickens and his collaborators reflect upon literary sociability, asking what it means to be territorial on the page.
Coda
Authors: Dasgupta Ushashi
Published: June 2020

The Coda discusses the changing representations of tenancy after Dickens’s death in 1870. It moves through the fin de siècle, offerings readings of novellas by Wilkie Collins and tracing Dickens’s legacy in these texts. Collins’s novellas use rented space as a prism through which to address broad concerns about modernity. The Coda briefly notes the role of rented space in works by George Gissing, Thomas Hardy, Henry James, and Bram Stoker. It concludes by shifting its focus to the twentieth and twenty-first centuries, and considers examples from literature, film, television, and contemporary installation art, including Tatzu Nishi’s 2002 project, Villa Victoria.
Trump’s America and its Impact on Energy Justice
Authors: Smith Don C. , Zillman Donald N.
Published: June 2020

This chapter involves the United States, with attention focused on President Donald Trump’s administration. After an overview of energy justice in the context of America in 2020, the chapter considers the Trump administration’s approach—or absence thereof—to the precepts of energy justice. The chapter begins with an assessment of President Trump. The following section describes the likely position of the Republican Party on issues of energy justice. That is followed by a more detailed examination of the Trump-Republican Party actions involving matters that illuminate their approach to energy with significant focus on climate change and the administration’s efforts to roll back essentially all of the climate change-related measures put into place by former President Barack Obama. Finally, the conclusion considers where governmental policies may be heading and suggests that the Trump agenda is very much a contested one.
Introduction
Authors: Morris Michael
Published: June 2020

The Introduction introduces the main claims of the book. It presents a paradox which arises for each of the art forms discussed, beginning with the case of painting (where it can be seen in Magritte’s painting of a pipe). It then presents a Non-Distraction Thesis, according to which attention to the medium of an artistic representation cannot inevitably be a distraction from attending to the content: it is a constraint on any acceptable treatment of the paradox that it must be consistent with this Non-Distraction Thesis. Finally, the Introduction briefly characterizes the solution to the paradox which the book offers for the cases of paintings, photographs, and novels.
Real Characters
Authors: Morris Michael
Published: June 2020

This chapter attempts to develop for the case of characters in novels the kind of Real-Likeness view developed for painted things in Chapter Two. It does this by developing a new view in the philosophy of language. First, it introduces the idea of non-transactional uses of language, which are not designed to get some everyday kind of task done. It is argued that this kind of use is found both in philosophy and in stage plays. Secondly, it develops a Real-Likeness view of the characters in stage plays, and argues that novels have narrators who are like such characters. And thirdly, it introduces the idea of verbal mimes, which are ways of using words to imitate real-world things. It is then argued that novels create real likenesses by means of verbal mimes. Finally, it is suggested that even proper names may be given a role in verbal mimes.
Alard Palenc: Bachelor of Theology and Socius of the Collège de Sorbonne
Authors: OSB Thomas Sullivan
Published: June 2020

This chapter discusses how Alard Palenc played an especially active role in the affairs of both the University of Paris and the Collège de Sorbonne between 1430 and his unexpected and unexplained death in August of 1433. From its earliest years, the Collège de Sorbonne was governed by a provisor and its day-to-day life managed by the assembly of the socii, each of whom could be chosen early in his career to exercise the important functions of prior and procurator. The prior's responsibilities included arranging house assignments, maintaining house discipline, presiding at the assemblies, and recording the assembly's minutes. The magnus procurator, assisted by two parvi procuratores, took care of the fiscal management of the house and its material wealth. While the care of the books was one of the procurator's original duties, the task passed to an annually elected librarian. Palenc would hold three of these appointments during his years at the Sorbonne: prior, procurator, and librarian. He was also a cleric of the diocese of Tournai, a member and proctor of the Picard Nation, and a lecturer in theology and ethics.
The Schoolboy’s Quill: Joseph Belcher and Latin Learning at Harvard College c. 1700
Authors: Delwiche Theodore R.
Published: June 2020

This chapter explores the seventeenth-century Latin declamations of Joseph Belcher at Harvard College. When engaged properly, these compositions offer up incredible insight into the history of education and reading in early America. While Belcher's declamations have long been available in Harvard's archives — and even recently digitized — no scholar has thus far examined this unique window into the world of Puritan learning in much detail. The manuscript's chimera status, as an American artefact entirely in Latin, could help explain this neglect. Historian Meyer Reinhold comments that for the better part of the twentieth century ‘there were no American intellectual historians with sufficient training in Greek and Roman antiquity, and no classicists with sophisticated knowledge of American history’. Only very recently have certain classicists and classically-trained historians begun to bridge this gap and turn their scholastic gaze once again to colonial America. The chapter's analysis hopes to build on this nascent project, but is in no way complete; these declamations offer insight into the work of just one student over the period of one to two years. Still, a more lucid image emerges of the actual practice of education at Harvard College.
Universities Scottish, Irish, and European: Lyon Playfair (1818–98) and University Reform
Authors: Anderson Robert
Published: June 2020

This chapter assesses Lyon Playfair's views on universities. Playfair was a Scottish scientist who became an administrator, a university professor, and a politician. He has been praised as ‘one of the chief architects of the system of technical education in Great Britain as it exists to-day’. As a Member of Parliament (MP), he had to engage with practical university problems, in England and Ireland as well as Scotland, as they arose on the political agenda. But his starting-point was Scotland, and in putting Scottish problems in a wider British and European context, Playfair was part of a distinctive nineteenth-century discourse. Scottish academics and intellectuals were stimulated to think in comparative terms by the obvious contrast between Scottish and English universities; by the need to adapt university education to new social needs; by discussions which surrounded major legislation in 1858 and 1889; and by the widely shared feeling that Scotland had a national system of education closer to continental than to English traditions.
The Correspondence and Unpublished Papers of Robert Persons, SJ, ed. Victor Houliston, Ginevra Crosignani, and Thomas M. McCoog, SJ (Toronto: Pontifical Institute of Mediaeval Studies, 2017).
Authors: Machielsen Jan
Published: June 2020

This chapter examines the volume on the letters and papers of the English Jesuit Robert Persons (1546–1610) — the most prominent of the leaders of the early English Mission — edited by Victor Houliston, Ginevra Crosignani, and Thomas M. McCoog, SJ. This volume covers the period in Persons's life from shortly after his expulsion from Balliol College in 1574 to the run up of the Spanish Armada in 1588. The letters in between give a first-hand account of a wide range of crucial events. They cover the conflicts between the Welsh and the English at the Venerable English College in Rome. They also give more than a glimpse into the fateful mission of Persons and Edmund Campion to England in 1580–1581. Letters usefully place this endeavour within the context of global Jesuit missions. The documents show the elitism of the Jesuits, preoccupied above all with the conversion of the gentry. The chapter then considers a number of considerable challenges faced by the editors in putting this correspondence together.
Realistic Prescriptivism
Authors: Zuckermann Ghil'ad
Published: June 2020

This chapter explores the futile lexpionage (lexical + espionage) of the Academy of the Hebrew Language. During the past century, Israeli has become the primary mode of communication in all domains of Israel’s public and private life. Issues of language are so sensitive in Israel that politicians are often involved. For example, in an article in Ha’aretz (21 June 2004), the late left-wing politician Yossi Sarid attacked the (most widespread) ‘common language of éser shékel’ as inarticulate and monstrous, and urged civilians to fight it and protect ‘Hebrew’. However, most Israelis say éser shékel ‘ten shekels’ rather than asar-á shkal-ím (original Hebrew pronunciation: [ʕǎśåˈrå ʃəqåˈli:m]), the former literally meaning ‘ten (masculine singular) shekel (masculine singular)’, the latter ‘ten (feminine singular) shekels (masculine plural)’, and thus having a ‘polarity-of-gender agreement’—with a feminine numeral and a masculine plural noun, which is a Biblical Hebrew norm, not so in Israeli. Brought into being by legislation in 1953 as the supreme institute for Hebrew, the Academy of the Hebrew Language prescribes standards for Israeli grammar, lexis (vocabulary), orthography, transcription, and vocalization (vowel marking) ‘based upon the study of Hebrew’s historical development’. This chapter critically analyses the Academy’s mission, as intriguingly—and in my view oxymoronically—defined in its constitution: ‘to direct the development of Hebrew in light of its nature’. It throws light on the dynamics within the committees’ meetings, and exposes some U-turn decisions made by the Academy.
Talknology in the Service of the Barngarla Language Reclamation
Authors: Zuckermann Ghil'ad
Published: June 2020

This chapter introduces the fascinating and multifaceted reclamation of the Barngarla Aboriginal language of Eyre Peninsula, South Australia. In 2012, the Barngarla community and I launched the reclamation of this sleeping beauty. The presence of three Barngarla populations, several hours drive apart, presents the revival linguist with a need for a sophisticated reclamation involving talknological innovations such as online chatting, newsgroups, as well as photo and resource sharing. The chapter provides a brief description of our activities so far and describes the Barngarla Dictionary App. The Barngarla reclamation demonstrates two examples of righting the wrong of the past: (1) A book written in 1844 in order to assist a German Lutheran missionary to introduce the Christian light to Aboriginal people (and thus to weaken their own spirituality), is used 170 years later (by a secular Jew) to assist the Barngarla Aboriginal people, who have been linguicided by Anglo-Australians, to reconnect with their very heritage. (2) Technology, used for invasion (ships), colonization (weapons), and stolen generations (governmental black cars kidnapping Aboriginal children from their mothers), is employed (in the form of an app) to assist the Barngarla to reconnect with their cultural autonomy, intellectual sovereignty, and spirituality.
Comum
Authors: Gibson Roy K.
Published: June 2020

The chapter begins with the foundation of Novum Comum, its layout, position and history in northern Italy. The effect of landscape on individuals is a modern Romantic trope. Pliny preserves the ancient idea of the effect of environment on groups, and gives Comum prominence as a way of suggesting that he shares the antique values of the Transpadana. A marked love of water is also evident in his life. His father died before Pliny was 14, and was perhaps an early supporter of Vespasian. Loyalty to the Flavians had deep family roots. Verginius Rufus of Milan, twice consul by the time Pliny was 7 or 8, was appointed as his guardian. Details of childhood are otherwise few. In his Confessions, Augustine provides a fuller account of the childhood of a promising future orator spent in a region far from Rome. Pliny was very unlikely to have shared Augustine’s (modern) sense of alienation from his childhood education.
Rome
Authors: Gibson Roy K.
Published: June 2020

This chapter begins with events in Rome from Pliny’s youth and early manhood: his education as an orator under Quintilian, first appearance in a trial, early steps along the cursus honorum towards entry into the senate, as well as first marriage and early friendships. It considers the apparent lack of a relationship between Pliny and Plutarch as evidence of the former’s love of rhetoric and literature rather than philosophy, before covering Pliny’s praetorship of 93–4 C.E., the trial of Baebius Massa, and the ‘treason’ trials of the ‘Stoic opposition’. Pliny’s record of continuing imperial favour under Domitian is somewhat at odds with his commentary, which asserts a stalled career. But it is not the praetorship that is a threat to Pliny’s integrity; rather his account of a subsequent post at the military treasury does not take care to avoid being potentially misleading. Later parts of the chapter look at the death of Domitian, accession of Nerva, attempted prosecution of Publicius Certus, death of first or second wife ‘Venuleia’, and subsequent marriage to Calpurnia, as well as the consulship of 100 C.E. under Trajan, and the Panegyricus. Pliny’s lack of interest in Rome’s cityscape is noted, alongside his success in the Centumviral court. Pliny’s high hopes for senatorial partnership with Trajan end in a hitherto undiagnosed pessimism and disillusion in Pliny.
OsHDA710-Mediated Histone Deacetylation Regulates Callus Formation of Rice Mature Embryo
Authors: Zhang Haidao , Guo Fu , Qi Peipei , Huang Yizi , Xie Yongyao , Xu Lei , Han Ning , Xu Lin , Bian Hongwu
Published: June 2020

Histone deacetylases (HDACs) play important roles in the regulation of eukaryotic gene expression. The role of HDACs in specialized transcriptional regulation and biological processes is poorly understood. In this study, we evaluated the global expression patterns of genes related to epigenetic modifications during callus initiation in rice. We found that the repression of HDAC activity by trichostatin A (TSA) or by OsHDA710 mutation (hda710) results in impaired callus formation of rice mature embryo and increased global histone H3 acetylation levels. The HDAC inhibition decreased auxin response and cell proliferation in callus formation. Meanwhile, the transcriptional repressors OsARF18 and OsARF22 were upregulated in the callus of hda710. The chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis demonstrated that the callus of hda710 exhibited enhanced histone H3 acetylation levels at the chromatin regions of OsARF18 and OsARF22. Furthermore, we found that OsARF18 and OsARF22 were regulated through OsHDA710 recruitment to their target loci. In addition, overexpression of OsARF18 decreased the transcription of downstream genes PLT1 and PLT2 and inhibited callus formation of the mature embryo. These results demonstrate that OsHDA710 regulates callus formation by suppressing repressive OsARFs via histone deacetylation during callus formation of rice mature embryo. This indicates that OsHDA710-mediated histone deacetylation is an epigenetic regulation pathway for maintaining auxin response during cell dedifferentiation.
On the Iterated Estimation of Dynamic Discrete Choice Games
Authors: Bugni Federico A , Bunting Jackson
Published: June 2020

We study the first-order asymptotic properties of a class of estimators of the structural parameters in dynamic discrete choice games. We consider $K$-stage policy iteration (PI) estimators, where $K$ denotes the number of PIs employed in the estimation. This class nests several estimators proposed in the literature. By considering a “pseudo likelihood” criterion function, our estimator becomes the $K$-pseudo maximum likelihood (PML) estimator in Aguirregabiria and Mira (2002, 2007). By considering a “minimum distance” criterion function, it defines a new $K$-minimum distance (MD) estimator, which is an iterative version of the estimators in Pesendorfer and Schmidt-Dengler (2008) and Pakes et al. (2007). First, we establish that the $K$-PML estimator is consistent and asymptotically normal for any $K \in \mathbb{N}$. This complements findings in Aguirregabiria and Mira (2007), who focus on $K=1$ and $K$ large enough to induce convergence of the estimator. Furthermore, we show under certain conditions that the asymptotic variance of the $K$-PML estimator can exhibit arbitrary patterns as a function of $K$. Second, we establish that the $K$-MD estimator is consistent and asymptotically normal for any $K \in \mathbb{N}$. For a specific weight matrix, the $K$-MD estimator has the same asymptotic distribution as the $K$-PML estimator. Our main result provides an optimal sequence of weight matrices for the $K$-MD estimator and shows that the optimally weighted $K$-MD estimator has an asymptotic distribution that is invariant to $K$. The invariance result is especially unexpected given the findings in Aguirregabiria and Mira (2007) for $K$-PML estimators. Our main result implies two new corollaries about the optimal $1$-MD estimator (derived by Pesendorfer and Schmidt-Dengler (2008)). First, the optimal $1$-MD estimator is efficient in the class of $K$-MD estimators for all $K \in \mathbb{N}$. In other words, additional PIs do not provide first-order efficiency gains relative to the optimal $1$-MD estimator. Second, the optimal $1$-MD estimator is more or equally efficient than any $K$-PML estimator for all $K \in \mathbb{N}$. Finally, the Appendix provides appropriate conditions under which the optimal $1$-MD estimator is efficient among regular estimators.
Postnatal Role of the Cytoskeleton in Adult Epileptogenesis
Authors: Gavrilovici Cezar , Jiang Yulan , Kiroski Ivana , Teskey G Campbell , Rho Jong M , Nguyen Minh Dang
Published: June 2020

Mutations in cytoskeletal proteins can cause early infantile and childhood epilepsies by misplacing newly born neurons and altering neuronal connectivity. In the adult epileptic brain, cytoskeletal disruption is often viewed as being secondary to aberrant neuronal activity and/or death, and hence simply represents an epiphenomenon. Here, we review the emerging evidence collected in animal models and human studies implicating the cytoskeleton as a potential causative factor in adult epileptogenesis. Based on the emerging evidence, we propose that cytoskeletal disruption may be an important pathogenic mechanism in the mature epileptic brain.
Chromosome-Scale Genome Assembly of Fusarium oxysporum Strain Fo47, a Fungal Endophyte and Biocontrol Agent
Authors: Wang Bo , Yu Houlin , Jia Yanyan , Dong Quanbin , Steinberg Christian , Alabouvette Claude , Edel-Hermann Veronique , Kistler H. Corby , Ye Kai , Ma Li-Jun , Guo Li
Published: June 2020

Here, we report a chromosome-level genome assembly of Fusarium oxysporum Fo47 (12 pseudomolecules; contig N50: 4.52 Mb), generated using a combination of PacBio long-read, Illumina paired end, and high-throughput chromosome conformation capture sequencing data. Although F. oxysporum causes vascular wilt to over 100 plant species, the strain Fo47 is classified as an endophyte and is widely used as a biocontrol agent for plant disease control. The Fo47 genome carries a single accessory chromosome of 4.23 Mb, compared with the reference genome of F. oxysporum f. sp. lycopersici Fol4287. The high-quality assembly and annotation of the Fo47 genome will be a valuable resource for studying the mechanisms underlying the endophytic interactions between F. oxysporum and plants as well as for deciphering the genome evolution of the F. oxysporum species complex.
Case Study: Effectiveness and Functioning of Biomedical Engineering Services and Impact on Quality Care at Fortis Escorts Hospital
Authors: Sonali Seep , Kapoor Taruna
Published: June 2020

This study was undertaken to analyze the effectiveness and functioning of engineering services and its impact on overall quality care. For this purpose, various parameters like maintenance strategy, repair and replacement policy used, frequency and reasons for equipment failure, maintenance cost, risk incurred due to failure, availability of alternative equipment, training, and skill development were assessed. Constructive results were obtained from the study, validating that engineering services do have an influential role in the health sector; without them, health quality will decline. Therefore, the reputation of a hospital depends greatly on the technology being used in the hospital.
Dickeya oryzae sp. nov., isolated from the roots of rice
Authors: Wang Xing , He Shan-Wen , Guo He-Bao , Han Ji-Gang , Thin kyu kyu , Gao Ju-sheng , Wang Yao , Zhang Xiao-Xia
Published: June 2020

A novel Gram-stain-negative strain, designated ZYY5T, was isolated from rice roots. Results of 16S rRNA gene analysis indicated that strain ZYY5T was a member of the genus

Dickeya

, with a highest similarity to

Dickeya zeae

DSM 18068T (98.5%). The major fatty acids were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). Multi-locus sequence analysis using five concatenated genes (16S rRNA, atpD, infB, recA and gyrB) and phylogenomic analysis based on 2940 core gene sequences showed that strain ZYY5T formed a robust cluster with strains EC1, ZJU1202, DZ2Q, NCPPB 3531 and CSL RW192, while separated from the other strains of

D. zeae

. The orthologous average nucleotide identity (ANI) and digital DNA–DNAhybridization (dDDH) values among these six strains ranged from 96.8–99.9% and 73.7–99.8%, which supported that they were belonged to the same species. However, strain ZYY5T shared 58.4 of dDDH and 94.5% of ANI values with type strain

D. zeae

DSM 18068T, which were lower than the proposed species boundary cut-off for dDDH and ANI. The genomic analysis revealed that strain ZYY5T contained virulence-associated genes, which is same as the phylogenetic-related strains of the genus

Dickeya

. Based on the results of the polyphasic approaches, we propose that strain ZYY5T represents a novel species in the genus

Dickeya

, for which the name Dickeya oryzae sp. nov. (=JCM 33020 T=ACCC 61554 T) is proposed. Strains EC1, ZJU1202, DZ2Q, NCPPB 3531 and CSL RW192 should also be classified in the same genomospecies of D. oryzae same as ZYY5T.
Pseudomonas defluvii sp. nov., isolated from hospital sewage
Authors: Qin Jiayuan , Hu Yiyi , Wu Wenjing , Feng Yu , Zong Zhiyong
Published: June 2020

A novel Gram-negative, obligate aerobic, mobile, rod-shaped and non-spore-forming bacterial strain, WCHP16T, was isolated from the wastewater treatment plant at West China Hospital in Chengdu, PR China. It was characterized using a polyphasic approach. Analysis of its 16S rRNA gene sequence showed that strain WCHP16T belonged to the genus

Pseudomonas

with the highest similarity to Pseudomonas qingdaonensis JJ3T (99.34 %),

Pseudomonas shirazica

VM14T (99.0 %),

Pseudomonas plecoglossicida

NBRC 103162T (99.0 %) and

Pseudomonas asiatica

RYU5T (99.0 %). Phylogenomic analysis based on 107 core gene sequences demonstrated that WCHP16T was a member of the

Pseudomonas putida

group but was distant from all closely related species. Whole-genome comparisons, using average nucleotide identity based on blast (ANIb) and in silico DNA–DNA hybridization (isDDH), confirmed low genome relatedness to all the known

Pseudomonas

species (below the recommended thresholds of 95 % [ANIb] and 70 % [isDDH] for species delineation). Phenotypic characterization tests showed that the utilization of phenylacetic acid and capric acid, but not d-arabitol, and inability to produce fluorescent (King B medium) in combination could distinguish this strain from other related species of the genus

Pseudomonas

. Therefore, based on genetic and phenotypic evidence, it is clear that strain WCHP16T represents a novel species, for which the name Pseudomonas defluvii sp. nov. is proposed. The type strain is WCHP16T (GDMCC1.1215T=CCTCC AB 2017103T=KCTC 52991T).
Genomic surveillance of Escherichia coli and Klebsiella spp. in hospital sink drains and patients
Authors: Constantinides Bede , Chau Kevin K. , Quan T. Phuong , Rodger Gillian , Andersson Monique I. , Jeffery Katie , Lipworth Sam , Gweon Hyun S. , Peniket Andy , Pike Graham , Millo Julian , Byukusenge Mary , Holdaway Matt , Gibbons Cat , Mathers Amy J. , Crook Derrick W. , Peto Timothy E.A. , Walker A. Sarah , Stoesser Nicole
Published: June 2020

Escherichia coli

and

Klebsiella

spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant

E. coli

and

Klebsiella

spp., particularly in the context of outbreaks of resistant strains amongst patients. Without focusing exclusively on resistance markers or a clinical outbreak, we demonstrate that many hospital sink drains are abundantly and persistently colonized with diverse populations of

E. coli

,

Klebsiella pneumoniae

and

Klebsiella oxytoca

, including both antimicrobial-resistant and susceptible strains. Using whole-genome sequencing of 439 isolates, we show that environmental bacterial populations are largely structured by ward and sink, with only a handful of lineages, such as

E. coli

ST635, being widely distributed, suggesting different prevailing ecologies, which may vary as a result of different inputs and selection pressures. Whole-genome sequencing of 46 contemporaneous patient isolates identified one (2 %; 95 % CI 0.05–11 %)

E. coli

urine infection-associated isolate with high similarity to a prior sink isolate, suggesting that sinks may contribute to up to 10 % of infections caused by these organisms in patients on the ward over the same timeframe. Using metagenomics from 20 sink-timepoints, we show that sinks also harbour many clinically relevant antimicrobial resistance genes including bla
CTX-M, bla
SHV and mcr, and may act as niches for the exchange and amplification of these genes. Our study reinforces the potential role of sinks in contributing to Enterobacterales infection and antimicrobial resistance in hospital patients, something that could be amenable to intervention. This article contains data hosted by Microreact.
COVID-19 PCR Test Performance for Samples Stored at Ambient Temperature
Authors: Agaoglu Nihat Bugra , Yıldız Jale , Dogan Ozlem Akgun , Alkurt Gizem , Kose Betsi , Demirkol Yasemin Kendir , Irvem Arzu , Doğanay Levent , Doganay Gizem Dinler
Published: June 2020

Background

The new type of Coronavirus infection had become a pandemic in a very short period since it was first seen in Wuhan. The outbreak had a negative impact on all health care systems throughout the world and overwhelmed the diagnostic laboratories as well. During the pandemic, handling patient specimens in accordance with the universal guidelines was troublesome as WHO, CDC and ECDC required cold chain compliance during transporting and storing the swap samples.

Materials and methods

In this study, we tested diagnostic performance of RT-PCR on 30 swab samples stored at ambient temperature and compared them with the samples stored at +4°C.

Results

Our results revealed that all the samples stored at ambient temperature remain PCR positive for at least five days. We did not see any false negativity.

Conclusion

In conclusion, we report that transferring and storing of nasopharyngeal/oropharyngeal samples at ambient temperature could be possible in the resource-limited conditions like pandemic.
Developing human fetal skin demonstrates a unique lymphocyte signature
Authors: Dhariwala Miqdad O. , Karthikeyan Dhuvarakesh , Vasquez Kimberly S. , Farhat Sepideh , Taravati Keyon , Leitner Elizabeth G. , Pauli Mariela , Lowe Margaret M. , Rosenblum Michael D. , Scharschmidt Tiffany C.
Published: June 2020

Lymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity, demonstrating a unique fetal skin lymphocyte signature. While most conventional αβ T (Tconv) cells in fetal skin have a naïve, proliferative phenotype, a subset of CD4+Tconv and CD8+cells demonstrate memory-like features and a propensity for IFNγ production. Skin regulatory T cells dynamically accumulate over the second trimester in temporal and regional association with hair follicle development. These fetal skin Tregs demonstrate an effector memory phenotype while differing from their adult counterparts in expression of key effector molecules. Thus, we identify features of prenatal skin lymphocytes that may have key implications for understanding antigen and allergen encountersin uteroand in infancy.
Gut microbial taxa elevated by dietary sugar disrupt memory function
Authors: Noble Emily E , Olson Christine A. , Davis Elizabeth , Tsan Linda , Chen Yen-Wei , Schade Ruth , Liu Clarissa , Suarez Andrea , Jones Roshonda B , de La Serre Claire , Yang Xia , Hsiao Elaine Y. , Kanoski Scott E
Published: June 2020

Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genusParabacteroides(P. distasonisandP. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereasParabacteroidesmicrobial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota “dysbiosis” in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.
Predicting transdermal fentanyl delivery using mechanistic simulations for tailored therapy
Authors: Defraeye Thijs , Bahrami Flora , Ding Lu , Malini Riccardo Innocenti , Terrier Alexandre , Rossi René M.
Published: June 2020

Transdermal drug delivery is a key technology for administering drugs. However, most devices are “one-size-fits-all”, even though drug diffusion through the skin varies significantly from person-to-person. For next-generation devices, personalization for optimal drug release would benefit from an augmented insight into the drug release and percutaneous uptake kinetics. Our objective was to quantify the changes in transdermal fentanyl uptake with regards to the patient’s age and the anatomical location where the patch was placed. We also explored to which extent the drug flux from the patch could be altered by miniaturizing the contact surface area of the patch reservoir with the skin. To this end, we used validated mechanistic modeling of fentanyl diffusion, storage, and partitioning in the epidermis to quantify drug release from the patch and the uptake within the skin. A superior spatiotemporal resolution compared to experimental methods enabledin-silicoidentification of peak concentrations and fluxes, and the amount of stored drug and bioavailability. The patients’ drug uptake showed a 36% difference between different anatomical locations after 72 h, but there was a strong interpatient variability. With aging, the drug uptake from the transdermal patch became slower and less potent. A 70-year-old patient received 26% less drug over the 72-h application period, compared to an 18-year-old patient. Additionally, a novel concept of using micron-sized drug reservoirs was exploredin silico. These reservoirs induced a much higher local flux (µg cm-2h-1) than conventional patches. Up to a 200-fold increase in the drug flux was obtained from these small reservoirs. This effect was mainly caused by transverse diffusion in the stratum corneum, which is not relevant for much larger conventional patches. These micron-sized drug reservoirs open new ways to individualize reservoir design and thus transdermal therapy. Such computer-aided engineering tools also have great potential forin-silicodesign and precise control of drug delivery systems. Here, the validated mechanistic models can serve as a key building block for developing digital twins for transdermal drug delivery systems.
Universal probabilistic programming offers a powerful approach to statistical phylogenetics
Authors: Ronquist Fredrik , Kudlicka Jan , Senderov Viktor , Borgström Johannes , Lartillot Nicolas , Lundén Daniel , Murray Lawrence , Schön Thomas B. , Broman David
Published: June 2020

Statistical phylogenetic analysis currently relies on complex, dedicated software packages, making it difficult for evolutionary biologists to explore new models and inference strategies. Recent years have seen more generic solutions based on probabilistic graphical models, but this formalism can only partly express phylogenetic problems. Here we show that universal probabilistic programming languages (PPLs) solve the expressivity problem, while still supporting automated generation of efficient inference algorithms. To prove the latter point, we develop automated generation of sequential Monte Carlo (SMC) algorithms for PPL descriptions of arbitrary biological diversification (birth-death) models. SMC is a new inference strategy for these problems, supporting both parameter inference and efficient estimation of Bayes factors that are used in model testing. We take advantage of this in automatically generating SMC algorithms for several recent diversification models that have been difficult or impossible to tackle previously. Finally, applying these algorithms to 40 bird phylogenies, we show that models with slowing diversification, constant turnover and many small shifts generally explain the data best. Our work opens up several related problem domains to PPL approaches, and shows that few hurdles remain before these techniques can be effectively applied to the full range of phylogenetic models.
Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection
Authors: Wei Jin , Alfajaro Mia Madel , Hanna Ruth E. , DeWeirdt Peter C. , Strine Madison S. , Lu-Culligan William J. , Zhang Shang-Min , Graziano Vincent R. , Schmitz Cameron O. , Chen Jennifer S. , Mankowski Madeleine C. , Filler Renata B. , Gasque Victor , de Miguel Fernando , Chen Huacui , Oguntuyo Kasopefoluwa , Abriola Laura , Surovtseva Yulia V. , Orchard Robert C. , Lee Benhur , Lindenbach Brett , Politi Katerina , van Dijk David , Simon Matthew D. , Yan Qin , Doench John G. , Wilen Craig B.
Published: June 2020

Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 and identified known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex and key components of the TGF-β signaling pathway. Small molecule inhibitors of these pathways prevented SARS-CoV-2-induced cell death. We also revealed that the alarmin HMGB1 is critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.
FSL-MRS: An end-to-end spectroscopy analysis package
Authors: Clarke William T , Stagg Charlotte J , Jbabdi Saad
Published: June 2020

Purpose

We introduce FSL-MRS, an end-to-end, modular, open-source magnetic resonance spectroscopy analysis toolbox. FSL-MRS provides spectroscopic data conversion, pre-processing, spectral simulation, fitting, quantitation and visualisation.

Methods

FSL-MRS is modular. FSL-MRS programs operate on data in a standard format (NIfTI) capable of storing single voxel and multi-voxel spectroscopy, including spatial orientation information.

FSL-MRS includes tools for pre-processing of raw spectroscopy data, including coil-combination, frequency and phase alignment, and filtering. A density matrix simulation program is supplied for generation of basis spectra from simple text-based descriptions of pulse sequences.

Fitting is based on linear combination of basis spectra and implements Markov chain Monte Carlo optimisation for the estimation of the full posterior distribution of metabolite concentrations. Validation of the fitting is carried out on independently created simulated data, phantom data, and three in vivo human datasets (257 SVS and 8 MRSI datasets) at 3T and 7T.

Interactive HTML reports are automatically generated by processing and fitting stages of the toolbox. FSL-MRS can be used on the command line or interactively in the Python language.

Results

Validation of the fitting shows low error in simulation (median error 11.9%) and in phantom (3.4%). Average correlation between a third-party toolbox (LCModel) and FSL-MRS was high (0.53-0.81) in all three in vivo datasets.

Conclusion

FSL-MRS is designed to be flexible and extensible to new forms of spectroscopic acquisitions. Custom fitting models can be specified within the framework for dynamic or multi-voxel spectroscopy. FSL-MRS is available as part of the FMRIB Software Library.
Oral administration of a single anti-CfaE nanobody provides broadly cross-protective immunity against major pathogenic EnterotoxigenicEscherichia colistrains
Authors: Amcheslavsky Alla , Wallace Aaron , Ejemel Monir , Li Qi , McMahon Conor , Stoppato Matteo , Giuntini Serena , Schiller Zachary A. , Pondish Jessica , Toomey Jacqueline R. , Schneider Ryan , Meisinger Jordan , Heukers Raimond , Kruse Andrew C. , Barry Elieen M. , Pierce Brian , Klempner Mark S. , Cavacini Lisa A. , Wang Yang
Published: June 2020

EnterotoxigenicEscherichia coli(ETEC) is estimated to cause approximately 380,000 deaths annually during sporadic or epidemic outbreaks worldwide. There is currently no vaccine licensed to prevent ETEC. Development of prophylaxis against ETEC is challenging due to the vast heterogeneity of the ETEC strains. The discovery of nanobodies has emerged as a successful new biologics in treating mucosal infectious disease as nanobodies can recognize conserved epitopes on hypervariable pathogens. In this study, we performed large screens using immunized llamas and a naïve nanobody yeast display library against adhesins of colonization factors. Cross-protective nanobodies were selected within vitroactivities inhibiting mannose-resistant hemagglutination (MRHA) against all eleven major pathogenic ETEC strains. Oral administration of nanobodies led to significant reduction of bacterial colonization in animals challenged with multiple ETEC strains. Structural analysis revealed novel conserved epitopes as critical structural features for pan-ETEC vaccine design.

Two of the lead nanobodies, 2R215 and 1D7, were further engineered as trimer or fused with human IgA Fc-fragments as fusionbodies. Oral administration of the trimers or fusionbodies protected mice from infection at a much lower dose compared to the monomeric format. Importantly, fusionbodies prevented infection as a pre-treatment when administrated 2 hours before ETEC challenge to the animals. Together, our study provides the first proof of concept that oral administration of a single nanobody could confer broad protection against major pathogenic ETEC strains. Technological advances in large-scale manufacturing of biological proteins in plants and microorganisms will make nanobody-based immunotherapy a potent and cost-effective prophylaxis or treatment for ETEC.
A non-spiking neuron model with dynamic leak to avoid instability in recurrent networks
Authors: Rongala Udaya B. , Enander Jonas M.D. , Kohler Matthias , Loeb Gerald E. , Jörntell Henrik
Published: June 2020

Recurrent circuitry components are distributed widely within the brain, including both excitatory and inhibitory synaptic connections. Recurrent neuronal networks have potential stability problems, perhaps a predisposition to epilepsy. More generally, instability risks making internal representations of information unreliable. To assess the inherent stability properties of such recurrent networks, we tested a linear summation, non-spiking neuron model with and without a ‘dynamic leak’, corresponding to the low-pass filtering of synaptic input current by the RC circuit of the biological membrane. We first show that the output of this neuron model, in either of its two forms, follows its input at a higher fidelity than a wide range of spiking neuron models across a range of input frequencies. Then we constructed fully connected recurrent networks with equal numbers of excitatory and inhibitory neurons and randomly distributed weights across all synapses. When the networks were driven by pseudorandom sensory inputs with varying frequency, the recurrent network activity tended to induce high frequency self-amplifying components, sometimes evident as distinct transients, which were not present in the input data. The addition of a dynamic leak based on known membrane properties consistently removed such spurious high frequency noise across all networks. Furthermore, we found that the neuron model with dynamic leak imparts a network stability that seamlessly scales with the size of the network, conduction delays, the input density of the sensory signal and a wide range of synaptic weight distributions. Our findings suggest that neuronal dynamic leak serves the beneficial function of protecting recurrent neuronal circuitry from the self-induction of spurious high frequency signals, thereby permitting the brain to utilize this architectural circuitry component regardless of network size or recurrency.

Author Summary

It is known that neurons of the brain are extensively interconnected, which can result in many recurrent loops within its neuronal network. Such loops are prone to instability. Here we wanted to explore the potential noise and instability that could result in recurrently connected neuronal networks across a range of conditions. To facilitate such simulations, we developed a non-spiking neuron model that captures the main characteristics of conductance-based neuron models of Hodgkin-Huxley type, but is more computationally efficient. We found that a so-called dynamic leak, which is a natural consequence of the way the membrane of the neuron is constructed and how the neuron integrates synaptic inputs, provided protection against spurious, high frequency noise that tended to arise in our recurrent networks of varying size. We propose that this linear summation model provides a stable and useful tool for exploring the computational behavior of recurrent neural networks.