bluuebunny/crossref_metadata_2025 huggingface dataset:
Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI) for Monitoring of Drug Response in Primary Cancer Spheroids
Authors: Mittal Parul , Price Zoe K , Lokman Noor A , Ricciardelli Carmela , Oehler Martin K , Klingler‐Hoffmann Manuela , Hoffmann Peter
Published: September 2019

Malignant ascites is a fluid, which builds up in the abdomen and contains cancer cells in the form of single cells or multicellular clusters called spheroids. Malignant ascites has been observed in patients suffering from ovarian, cervical, gastric, colorectal, pancreatic, endometrial, or primary liver cancer. The spheroids are believed to play a major role in chemo resistance and metastasis of the cancer. To ease the discomfort of patients, malignant ascites (MA) is often drained from the abdomen using a procedure called paracentesis. MA retrieved via this minimal invasive procedure is a great source for cancer spheroids, which can be used for testing chemotherapeutic drugs and drug combinations. Herein, the existing workflow is adapted to make concurrent monitoring of drug accumulation, drug response, and drug metabolites feasible using primary spheroids or spheroids grown without a scaffolding matrix. To achieve this, those spheroids are embedded in matrigel, before fixing them with formalin. This makes it possible to process, store, and ship samples at room temperature. This new approach might be used to choose the best targeted therapy for each patient and thereby facilitate personalized medicine.
Internal plasticization of poly(vinyl) chloride using glutamic acid as a branched linker to incorporate four plasticizers per anchor point
Authors: Li Longbo , Tek Andy T. , Wojtecki Rudy J. , Braslau Rebecca
Published: September 2019

Internal plasticization of polyvinyl chloride (PVC) using thermal azide‐alkyne Huisgen dipolar cycloaddition between azidized PVC and electron‐poor acetylenediamides incorporating a branched glutamic acid linker resulted in incorporation of four plasticizing moieties per attachment point on the polymer chain. A systematic study incorporating either alkyl or polyethylene glycol esters provided materials with varying degrees of plasticization, with depressed Tg values ranging from −1 °C to 62 °C. Three interesting trends were observed. First, Tg values of PVC bearing various internal plasticizers were shown to decrease with increasing chain length of the plasticizing ester. Second, branched internal plasticizers bearing triethylene glycol chains had lower Tg values compared to those with similar length long‐chain alkyl groups. Finally, thermogravimetric analysis of these internally plasticized PVC samples revealed that these branched internal plasticizers bearing alkyl chains are more thermally stable than similarity branched plasticizers bearing triethylene glycol units. These internal tetra‐plasticizers were synthesized and attached to PVC‐azide in three simple synthetic steps. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1821–1835
Selling in Spanish and/or English: A study of Hispanic direct sellers
Authors: Canziani Bonnie F. , Welsh Dianne H. B. , Ramadani Veland
Published: September 2019

Exploring differences within a U.S. sample of Hispanic direct sellers provides insights into the impact of acculturation on satisfaction survey responses. The scope of the study is constrained to sellers who self‐identified ethnically as Latino/Hispanic on a U.S. national survey of direct sellers. Findings show evidence of cultural heterogeneity within this sample of Hispanic direct sellers that corresponds to their uses of English and Spanish in selling activities. Practical implications suggest that Spanish Dominant Sellers claim higher satisfaction ratings and higher performance estimates than do English Dominant Sellers. English Dominant Sellers indicate greater use of Web 2.0 technologies for selling. Implications and future studies are discussed.
Symmetry algebras of stringy cosets
Authors: Kumar Dushyant , Sharma Menika
Published: September 2019

Abstract

We find the symmetry algebras of cosets which are generalizations of the minimal-model cosets, of the specific form

$$ \frac{\mathrm{SU}{(N)}_k\times \mathrm{SU}{(N)}_{\mathrm{\ell}}}{\mathrm{SU}{(N)}_{k+\mathrm{\ell}}} $$

SU

N

k

×
SU

N

ℓ

SU

N

k
+
ℓ

. We study this coset in its free field limit, with k, ℓ → ∞, where it reduces to a theory of free bosons. We show that, in this limit and at large N, the algebra

$$ {\mathcal{W}}_{\infty}^e\left[1\right] $$

W
∞
e

1

emerges as a sub-algebra of the coset algebra. The full coset algebra is a larger algebra than conventional

$$ \mathcal{W} $$

W

-algebras, with the number of generators rising exponentially with the spin, characteristic of a stringy growth of states. We compare the coset algebra to the symmetry algebra of the large N symmetric product orbifold CFT, which is known to have a stringy symmetry algebra labelled the ‘higher spin square’. We propose that the higher spin square is a sub-algebra of the symmetry algebra of our stringy coset.
Aerobic exercise training improves hepatic and muscle insulin sensitivity, but reduces splanchnic glucose uptake in obese humans with type 2 diabetes
Authors: Gregory Justin M. , Muldowney James A. , Engelhardt Brian G. , Tyree Regina , Marks-Shulman Pam , Silver Heidi J. , Donahue E. Patrick , Edgerton Dale S. , Winnick Jason J.
Published: September 2019

Background

Aerobic exercise training is known to have beneficial effects on whole-body glucose metabolism in people with type 2 diabetes (T2D). The responses of the liver to such training are less well understood. The purpose of this study was to determine the effect of aerobic exercise training on splanchnic glucose uptake (SGU) and insulin-mediated suppression of endogenous glucose production (EGP) in obese subjects with T2D.

Methods

Participants included 11 obese humans with T2D, who underwent 15 ± 2 weeks of aerobic exercise training (AEX; n = 6) or remained sedentary for 15 ± 1 weeks (SED; n = 5). After an initial screening visit, each subject underwent an oral glucose load clamp and an isoglycemic/two-step (20 and 40 mU/m2/min) hyperinsulinemic clamp (ISO-clamp) to assess SGU and insulin-mediated suppression of EGP, respectively. After the intervention period, both tests were repeated.

Results

In AEX, the ability of insulin to suppress EGP was improved during both the low (69 ± 9 and 80 ± 6% suppression; pre-post, respectively; p < 0.05) and high (67 ± 6 and 82 ± 4% suppression, respectively; p < 0.05) insulin infusion periods. Despite markedly improved muscle insulin sensitivity, SGU was reduced in AEX after training (22.9 ± 3.3 and 9.1 ± 6.0 g pre-post in AEX, respectively; p < 0.05).

Conclusions

In obese T2D subjects, exercise training improves whole-body glucose metabolism, in part, by improving insulin-mediated suppression of EGP and enhancing muscle glucose uptake, which occur despite reduced SGU during an oral glucose challenge.
The effect of cysteine oxidation on DJ-1 cytoprotective function in human alveolar type II cells
Authors: Bahmed Karim , Boukhenouna Samia , Karim Loukmane , Andrews Tessa , Lin Jiusheng , Powers Robert , Wilson Mark A. , Lin Chih-Ru , Messier Elise , Reisdorph Nichole , Powell Roger L. , Tang Hsin-Yao , Mason Robert J. , Criner Gerard J. , Kosmider Beata
Published: September 2019

DJ-1 is a multifunctional protein with cytoprotective functions. It is localized in the cytoplasm, nucleus, and mitochondria. The conserved cysteine residue at position 106 (Cys106) within DJ-1 serves as a sensor of redox state and can be oxidized to both the sulfinate (-SO2−) and sulfonate (-SO3−) forms. DJ-1 with Cys106-SO2− has cytoprotective activity but high levels of reactive oxygen species can induce its overoxidation to Cys106-SO3−. We found increased oxidative stress in alveolar type II (ATII) cells isolated from emphysema patients as determined by 4-HNE expression. DJ-1 with Cys106-SO3− was detected in these cells by mass spectrometry analysis. Moreover, ubiquitination of Cys106-SO3− DJ-1 was identified, which suggests that this oxidized isoform is targeted for proteasomal destruction. Furthermore, we performed controlled oxidation using H2O2 in A549 cells with DJ-1 knockout generated using CRISPR-Cas9 strategy. Lack of DJ-1 sensitized cells to apoptosis induced by H2O2 as detected using Annexin V and propidium iodide by flow cytometry analysis. This treatment also decreased both mitochondrial DNA amount and mitochondrial ND1 (NADH dehydrogenase 1, subunit 1) gene expression, as well as increased mitochondrial DNA damage. Consistent with the decreased cytoprotective function of overoxidized DJ-1, recombinant Cys106-SO3− DJ-1 exhibited a loss of its thermal unfolding transition, mild diminution of secondary structure in CD spectroscopy, and an increase in picosecond–nanosecond timescale dynamics as determined using NMR. Altogether, our data indicate that very high oxidative stress in ATII cells in emphysema patients induces DJ-1 overoxidation to the Cys106-SO3− form, leading to increased protein flexibility and loss of its cytoprotective function, which may contribute to this disease pathogenesis.
A novel miRNA identified in GRSF1 complex drives the metastasis via the PIK3R3/AKT/NF-κB and TIMP3/MMP9 pathways in cervical cancer cells
Authors: Sun Qi , Yang Zhen , Li Pu , Wang Xu , Sun Lu , Wang Shixing , Liu Min , Tang Hua
Published: September 2019

microRNAs (miRNAs) play an important role in carcinogenesis. Typically, miRNAs downregulate the target expression by binding to the 3′ UTR of mRNAs. However, recent studies have demonstrated that miRNAs can upregulate target gene expression, but its mechanism is not fully understood. We previously found that G-rich RNA sequence binding protein (GRSF1) mediates upregulation of miR-346 on hTERT gene. To explore whether GRSF1 mediate other miRNA’s upregulation on their target genes, we obtained profile of GRSF1-bound miRNAs by Flag-GRSF1-RIP-deep sequencing and found 12 novel miRNAs, named miR-G. In this study, we focused on miR-G-10, which is highly expressed in cervical cancer tissues and cell lines and serum from patients with metastatic cervical cancer. miR-G-10 in cervical cancer cells significantly promoted migration/invasion and anoikis resistance in vitro and lung metastasis in vivo. Furthermore, miR-G-10 bound to the 3′ UTR of PIK3R3 and upregulated its expression to activate the AKT/NF-κB signal pathway in a GRSF1-dependent manner, whereas miR-G-10 suppressed TIMP3 in the AGO2 complex to modulate the MMP9 signaling pathway in cervical cancer cells. Taken together, our findings may provide a new insight into the upregulation mechanism mediated by miRNAs and a potential biomarker for cervical cancer.
Author Correction: Comparison of livestock-associated and community-associated Staphylococcus aureus pathogenicity in a mouse model of skin and soft tissue infection
Authors: Randad Pranay R. , Dillen Carly A. , Ortines Roger V. , Mohr David , Aziz Maliha , Price Lance B. , Kaya Hülya , Larsen Jesper , Carroll Karen C. , Smith Tara C. , Miller Lloyd S. , Heaney Christopher D.
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Main spectral features of meteors studied using a terawatt-class high-power laser
Authors: Ferus M. , Kubelík P. , Petera L. , Lenža L. , Koukal J. , Křivková A. , Laitl V. , Knížek A. , Saeidfirozeh H. , Pastorek A. , Kalvoda T. , Juha L. , Dudžák R. , Civiš S. , Chatzitheodoridis E. , Krůs M.
Published: September 2019

Context. Meteor spectra are commonly interpreted using data from databases and tables. Several studies have demonstrated very sophisticated calculations of elemental compositions of meteoroid bodies based on the computation of synthetic meteor spectra or on the spectral analysis of airglow plasma containing evaporated, atomized, and ionized meteoroid matter. However, considering accuracy, reliability of computations, lack of laboratory experimental data in this field, as well as the complicated physical structure of meteor plasma, such qualitative assignment or quantitative calculations are still extensively discussed in the scientific community. Even on the laboratory level, many studies have shown the high complexity of the acquisition and interpretation of the data that are recorded with techniques of emission spectroscopy that are in fashion and philosophy similar to the spectral analysis of meteor plasma, that is, detection and quantification of the elements that are ablated from complicated multicomponent matrices.

Aims. The current study is focused on the application of terawatt-class laser-induced breakdown spectroscopy (TC-LIBS) of real samples of chondritic meteorites. We recorded emission spectra with high resolution and high precision that contain spectral lines that are typical for real meteoric spectra. Experimental data were compiled in a form that is convenient for the meteoric spectra interpretation and calibration.

Methods. TC-LIBS was carried out by a high-power terawatt-class laser facility, the Prague Asterix Laser System (PALS). The spectra were simultaneously recorded by an echelle high-resolution spectrograph in the UV/VIS spectral ranges and by a low-resolution spectrograph that was used for real observation of meteor spectra. We also present calculated synthetic spectra based on data from the NIST atomic spectra database.

Results. We assembled etalon qualitative tables of major meteoric spectral features that can be used both for the spectral wavelength calibration of low-resolution observational instruments and for the exact interpretation of meteor spectra. The data are compared with real meteor spectra.
Pudding Economics: Franklin’s “The Way to Wealth” and the Transactional Self
Authors: Horwitz Howard
Published: September 2019

Benjamin Franklin’s preface to the 1758 edition of Poor Richard’s Almanack, usually titled “The Way to Wealth,” is generally regarded as a sermon on frugality. The very form of the 1758 Preface, with Richard Saunders’s voice framing Father Abraham’s “Harangue,” ironizes Father Abraham’s doctrine of frugality. The effect of this literary performance is to illustrate or even stimulate desire for social interaction that is not frugal in any strict sense, but rather manifests an impulse to expand intercourse. The 1758 preface and Franklin’s extensive writings on economics present an expansive vision of capital formation. Commerce must grow incessantly, not for the accumulation of capital per se but for the prospect of endless growth, to spur and sustain what Adam Smith called “the progressive state.” Franklin’s economic writings delineate the constitution of the subject populating progressive society. Identity and ultimately the character of society are fabricated through ongoing, visible, and expanding transactions. Expansive or progressive identity is not illusory, but constitutive. Self and society must be creditable. This conceptualization was central to economic policy-making in the new nation; it straddles neoliberal critiques of subjectification in late capitalism.
Identifying molecular recognition features in intrinsically disordered regions of proteins by transfer learning
Authors: Hanson Jack , Litfin Thomas , Paliwal Kuldip , Zhou Yaoqi
Published: September 2019

Motivation

Protein intrinsic disorder describes the tendency of sequence residues to not fold into a rigid three-dimensional shape by themselves. However, some of these disordered regions can transition from disorder to order when interacting with another molecule in segments known as molecular recognition features (MoRFs). Previous analysis has shown that these MoRF regions are indirectly encoded within the prediction of residue disorder as low-confidence predictions [i.e. in a semi-disordered state P(D)≈0.5]. Thus, what has been learned for disorder prediction may be transferable to MoRF prediction. Transferring the internal characterization of protein disorder for the prediction of MoRF residues would allow us to take advantage of the large training set available for disorder prediction, enabling the training of larger analytical models than is currently feasible on the small number of currently available annotated MoRF proteins. In this paper, we propose a new method for MoRF prediction by transfer learning from the SPOT-Disorder2 ensemble models built for disorder prediction.

Results

We confirm that directly training on the MoRF set with a randomly initialized model yields substantially poorer performance on independent test sets than by using the transfer-learning-based method SPOT-MoRF, for both deep and simple networks. Its comparison to current state-of-the-art techniques reveals its superior performance in identifying MoRF binding regions in proteins across two independent testing sets, including our new dataset of >800 protein chains. These test chains share <30% sequence similarity to all training and validation proteins used in SPOT-Disorder2 and SPOT-MoRF, and provide a much-needed large-scale update on the performance of current MoRF predictors. The method is expected to be useful in locating functional disordered regions in proteins.

Availability and implementation

SPOT-MoRF and its data are available as a web server and as a standalone program at: http://sparks-lab.org/jack/server/SPOT-MoRF/index.php.

Supplementary information

Supplementary data are available at Bioinformatics online.
Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson’s disease
Authors: McCoy Brónagh , Jahfari Sara , Engels Gwenda , Knapen Tomas , Theeuwes Jan
Published: September 2019

McCoy et al. show that dopaminergic medication in Parkinson’s disease leads to changes in striatal signalling and in behaviour during learning, but that changes are specific to the processing of negative reinforcements. These within-patient changes are predictive of changes in future value-based choice behaviour and striatal responses.
Rising Powers and Grassroots Image Management: Confucius Institutes and China in the Media
Authors: Brazys Samuel , Dukalskis Alexander
Published: September 2019

This article proposes and tests a mechanism of grassroots image management to explain how rising powers craft an international environment more conducive to their interests. The aim is to promote the state’s foreign policy goals by influencing the perceptions of ordinary foreign citizens. To test this mechanism, we examine the impact of China’s Confucius Institutes (CIs) as an observable instrument of China’s grassroots image management strategy. Using data from the Global Database of Events, Language, and Tone (GDELT), we employ a spatial–temporal approach which finds that proximity to an active CI significantly and substantively improves the tone of media reporting about events relevant to China in that locality. The finding is robust to different specifications and estimation strategies, and is qualitatively consistent with results generated using household opinion data from Afrobarometer surveys. Theoretically, our results suggest the importance of systematically examining presentations and perceptions about rising powers at the popular level, in addition to focusing on elite attitudes, to understand discursive change. More directly, our findings reveal that CIs are helping to improve how China is viewed among foreign publics.
Predominance of soil vs root effect in rhizosphere microbiota reassembly
Authors: Zhao Mengli , Yuan Jun , Shen Zongzhuan , Dong Menghui , Liu Hongjun , Wen Tao , Li Rong , Shen Qirong
Published: September 2019

Rhizosphere community assembly is simultaneously affected by both plants and bulk soils and is vital for plant health. However, it is still unclear how and to what extent disease-suppressive rhizosphere microbiota can be constructed from bulk soil, and the underlying agents involved in the process that render the rhizosphere suppressive against pathogenic microbes remain elusive. In this study, the evolutionary processes of the rhizosphere microbiome were explored based on transplanting plants previously growing in distinct disease-incidence soils to one disease-suppressive soil. Our results showed that distinct rhizoplane bacterial communities were assembled on account of the original bulk soil communities with different disease incidences. Furthermore, the bacterial communities in the transplanted rhizosphere were noticeably influenced by the second disease-suppressive microbial pool, rather than that of original formed rhizoplane microbiota and homogenous nontransplanted rhizosphere microbiome, contributing to a significant decrease in the pathogen population. In addition, Spearman's correlations between relative abundances of bacterial taxa and the abundance of Ralstonia solanacearum indicated Anoxybacillus, Flavobacterium, Permianibacter and Pseudomonas were predicted to be associated with disease-suppressive function formation. Altogether, our results showed that bulk soil played an important role in the process of assembling and reassembling the rhizosphere microbiome of plants.
Construction of conformal maps based on the locations of singularities for improving the double exponential formula
Authors: Kyoya Shunki , Tanaka Ken’ichiro
Published: September 2019

The double exponential formula, or DE formula, is a high-precision integration formula using a change of variables called a DE transformation; it has the disadvantage that it is sensitive to singularities of an integrand near the real axis. To overcome this disadvantage, Slevinsky & Olver (2015, On the use of conformal maps for the acceleration of convergence of the trapezoidal rule and Sinc numerical methods. SIAM J. Sci. Comput., 37, A676–A700) attempted to improve the formula by constructing conformal maps based on the locations of singularities. Based on their ideas, we construct a new transformation formula. Our method employs special types of the Schwarz–Christoffel transformation for which we can derive the explicit form. The new transformation formula can be regarded as a generalization of DE transformations. We confirm its effectiveness by numerical experiments.
Nonsmooth algorithms for minimizing the largest eigenvalue with applications to inner numerical radius
Authors: Kangal Fatih , Mengi Emre
Published: September 2019

Nonsmoothness at optimal points is a common phenomenon in many eigenvalue optimization problems. We consider two recent algorithms to minimize the largest eigenvalue of a Hermitian matrix dependent on one parameter, both proven to be globally convergent unaffected by nonsmoothness. One of these algorithms models the eigenvalue function with a piece-wise quadratic function and is effective in dealing with nonconvex problems. The other algorithm projects the Hermitian matrix into subspaces formed of eigenvectors and is effective in dealing with large-scale problems. We generalize the latter slightly to cope with nonsmoothness. For both algorithms we analyze the rate of convergence in the nonsmooth setting, when the largest eigenvalue is multiple at the minimizer and zero is strictly in the interior of the generalized Clarke derivative, and prove that both algorithms converge rapidly. The algorithms are applied to, and the deduced results are illustrated on the computation of the inner numerical radius, the modulus of the point on the boundary of the field of values closest to the origin, which carries significance for instance for the numerical solution of a symmetric definite generalized eigenvalue problem and the iterative solution of a saddle point linear system.
Sonic ‘Detheatricalization’: Jean Cocteau, Film Music, and ‘Les Parents Terribles’
Authors: Anderson Laura
Published: September 2019

Jean Cocteau’s adaptation of his controversial play Les Parents terribles for the screen stands out in his oeuvre as an attempt to reconcile theatre and cinema. It also presented a challenge in preparing a soundscape for a work that did not have any music in its original form. Parents occupies a unique, Janus-like position in the history of French film music, as forward-looking in its anticipation of New Wave treatment of music as material as it is representative of the turn to adapting stage plays for the screen that started in the 1930s. Drawing on production sketchbooks and testimonies, this article considers the development of Cocteau’s working method and his collaboration with Georges Auric, fuelled by the director’s desire to take control of sonic matters. The resulting employment of a monothematic score was not only a new solution to the famous problem of filmed theatre, ‘detheatricalizing’ Parents sonically and visually, it contributed considerably to the development of Cocteau’s status as film auteur—one whose role now extended to adapting musical material. Furthermore, the effect of this compositional technique in Parents suggests that it can be fruitfully situated in relation to recent work in film music studies on issues of anempathetic scoring practices.
From the far-ultraviolet to the far-infrared – galaxy emission at 0 ≤ z ≤ 10 in the shark semi-analytic model
Authors: Lagos Claudia del P , Robotham Aaron S G , Trayford James W , Tobar Rodrigo , Bravo Matías , Bellstedt Sabine , Davies Luke J M , Driver Simon P , Elahi Pascal J , Obreschkow Danail , Power Chris
Published: September 2019

We combine the shark semi-analytic model of galaxy formation with the prospect software tool for spectral energy distribution (SED) generation to study the multiwavelength emission of galaxies from the far-ultraviolet (FUV) to the far-infrared (FIR) at 0 ≤ z ≤ 10. We produce a physical model for the attenuation of galaxies across cosmic time by combining a local Universe empirical relation to compute the dust mass of galaxies from their gas metallicity and mass, attenuation curves derived from radiative transfer calculations of galaxies in the eagle hydrodynamic simulation suite, and the properties of shark galaxies. We are able to produce a wide range of galaxies, from the z = 8 star-forming galaxies with almost no extinction, z = 2 submillimetre galaxies, down to the normal star-forming and red-sequence galaxies at z = 0. Quantitatively, we find that shark reproduces the observed (i) z = 0 FUV-to-FIR, (ii) 0 ≤ z ≤ 3 rest-frame K-band, and (iii) 0 ≤ z ≤ 10 rest-frame FUV luminosity functions, (iv) z ≤ 8 UV slopes, (v) the FUV-to-FIR number counts (including the widely disputed 850 μm), (vi) redshift distribution of bright $850\, \mu$m galaxies, and (vii) the integrated cosmic SED from z = 0 to 1 to an unprecedented level. This is achieved without the need to invoke changes in the stellar initial mass function, dust-to-metal mass ratio, or metal enrichment time-scales. Our model predicts star formation in galaxy discs to dominate in the FUV-to-optical, while bulges dominate at the NIR at all redshifts. The FIR sees a strong evolution in which discs dominate at z ≤ 1 and starbursts (triggered by both galaxy mergers and disc instabilities, in an even mix) dominate at higher redshifts, even out to z = 10.
Progenitors and explosion properties of supernova remnants hosting central compact objects: I. RCW 103 associated with the peculiar source 1E 161348−5055
Authors: Braun C , Safi-Harb S , Fryer C L
Published: September 2019

We present a Chandra and XMM–Newton imaging and spectroscopic study of the supernova remnant (SNR) RCW 103 (G332.4−00.4) containing the central compact object 1E 161348−5055. The high-resolution Chandra X-ray images reveal enhanced emission in the south-eastern and north-western regions. Equivalent width line images of Fe L, Mg, Si, and S using XMM–Newton data were used to map the distribution of ejecta. The SNR was sectioned into 56 regions best characterized by two-component thermal models. The harder component (kT ∼ 0.6 keV) is adequately fitted by the VPSHOCK non-equilibrium ionization model with an ionization time-scale net ∼ 1011–1012 cm−3 s, and slightly enhanced abundances over solar values. The soft component (kT ∼ 0.2 keV), fitted by the APEC model, is well described by plasma in collisional ionization equilibrium with abundances consistent with solar values. Assuming a distance of 3.1 kpc and a Sedov phase of expansion into a uniform medium, we estimate an SNR age of 4.4 kyr, a swept-up mass Msw = 16$f_\mathrm{ s}^{-1/2}$ D$_{3.1}^{5/2}$ M⊙, and a low explosion energy E* = 3.7 × 1049 $f_\mathrm{ s}^{-1/2}$ D$_{3.1}^{5/2}$ erg. This energy could be an order of magnitude higher if we relax the Sedov assumption, the plasma has a low filling factor, the plasma temperature is underestimated, or if the SNR is expanding into the progenitor’s wind-blown bubble. Standard explosion models did not match the ejecta yields. By comparing the fitted abundances to the most recent core-collapse nucleosynthesis models, our best estimate yields a low-mass progenitor of around 12–13 M⊙, lower than previously reported. We discuss degeneracies in the model fitting, particularly the effect of altering the explosion energy on the progenitor mass estimate.
A protein architecture guided screen for modification dependent restriction endonucleases
Authors: Lutz Thomas , Flodman Kiersten , Copelas Alyssa , Czapinska Honorata , Mabuchi Megumu , Fomenkov Alexey , He Xinyi , Bochtler Matthias , Xu Shuang-yong
Published: September 2019

Modification dependent restriction endonucleases (MDREs) often have separate catalytic and modification dependent domains. We systematically looked for previously uncharacterized fusion proteins featuring a PUA or DUF3427 domain and HNH or PD-(D/E)XK catalytic domain. The enzymes were clustered by similarity of their putative modification sensing domains into several groups. The TspA15I (VcaM4I, CmeDI), ScoA3IV (MsiJI, VcaCI) and YenY4I groups, all featuring a PUA superfamily domain, preferentially cleaved DNA containing 5-methylcytosine or 5-hydroxymethylcytosine. ScoA3V, also featuring a PUA superfamily domain, but of a different clade, exhibited 6-methyladenine stimulated nicking activity. With few exceptions, ORFs for PUA-superfamily domain containing endonucleases were not close to DNA methyltransferase ORFs, strongly supporting modification dependent activity of the endonucleases. DUF3427 domain containing fusion proteins had very little or no endonuclease activity, despite the presence of a putative PD-(D/E)XK catalytic domain. However, their expression potently restricted phage T4gt in Escherichia coli cells. In contrast to the ORFs for PUA domain containing endonucleases, the ORFs for DUF3427 fusion proteins were frequently found in defense islands, often also featuring DNA methyltransferases.
Oxazinomycin arrests RNA polymerase at the polythymidine sequences
Authors: Prajapati Ranjit K , Rosenqvist Petja , Palmu Kaisa , Mäkinen Janne J , Malinen Anssi M , Virta Pasi , Metsä-Ketelä Mikko , Belogurov Georgiy A
Published: September 2019

Oxazinomycin is a C-nucleoside antibiotic that is produced by Streptomyces hygroscopicus and closely resembles uridine. Here, we show that the oxazinomycin triphosphate is a good substrate for bacterial and eukaryotic RNA polymerases (RNAPs) and that a single incorporated oxazinomycin is rapidly extended by the next nucleotide. However, the incorporation of several successive oxazinomycins or a single oxazinomycin in a certain sequence context arrested a fraction of the transcribing RNAP. The addition of Gre RNA cleavage factors eliminated the transcriptional arrest at a single oxazinomycin and shortened the nascent RNAs arrested at the polythymidine sequences suggesting that the transcriptional arrest was caused by backtracking of RNAP along the DNA template. We further demonstrate that the ubiquitous C-nucleoside pseudouridine is also a good substrate for RNA polymerases in a triphosphorylated form but does not inhibit transcription of the polythymidine sequences. Our results collectively suggest that oxazinomycin functions as a Trojan horse substrate and its inhibitory effect is attributable to the oxygen atom in the position corresponding to carbon five of the uracil ring.
Conventional MRI radiomics in patients with suspected early- or pseudo-progression
Authors: Bani-Sadr Alexandre , Eker Omer Faruk , Berner Lise-Prune , Ameli Roxana , Hermier Marc , Barritault Marc , Meyronet David , Guyotat Jacques , Jouanneau Emmanuel , Honnorat Jerome , Ducray François , Berthezene Yves
Published: September 2019

Background

After radiochemotherapy, 30% of patients with early worsening MRI experience pseudoprogression (Psp) which is not distinguishable from early progression (EP). We aimed to assess the diagnostic value of radiomics in patients with suspected EP or Psp.

Methods

Radiomics features (RF) of 76 patients (53 EP and 23 Psp) retrospectively identified were extracted from conventional MRI based on four volumes-of-interest. Subjects were randomly assigned into training and validation groups. Classification model (EP versus Psp) consisted of a random forest algorithm after univariate filtering. Overall (OS) and progression-free survivals (PFS) were predicted using a semi-supervised principal component analysis, and forecasts were evaluated using C-index and integrated Brier scores (IBS).

Results

Using 11 RFs, radiomics classified patients with 75.0% and 76.0% accuracy, 81.6% and 94.1% sensitivity, 50.0% and 37.5% specificity, respectively, in training and validation phases. Addition of MGMT promoter status improved accuracy to 83% and 79.2%, and specificity to 63.6% and 75%. OS model included 14 RFs and stratified low- and high-risk patients both in the training (hazard ratio [HR], 3.63; P = .002) and the validation (HR, 3.76; P = .001) phases. Similarly, PFS model stratified patients during training (HR, 2.58; P = .005) and validation (HR, 3.58; P = .004) phases using 5 RF. OS and PFS forecasts had C-index of 0.65 and 0.69, and IBS of 0.122 and 0.147, respectively.

Conclusions

Conventional MRI radiomics has promising diagnostic value, especially when combined with MGMT promoter status, but with moderate specificity. In addition, our results suggest a potential for predicting OS and PFS.
Believing and Unbelieving in the Dunciad
Authors: Gee Sophie
Published: September 2019

In The Dunciad in Four Books Pope aimed his satire at the literary and intellectual world of eighteenth-century London, and especially its scholars, editors, and publishers. But Pope’s satire is also directed against contemporary developments in religion and theology. This chapter argues that Pope attacks fashionable ideas about the nature of God and the material world in The Dunciad as a way to explore his own ideas about the complex, often-paradoxical nature of imaginative fiction. Through allusions to the religious debates of his day, Pope encourages readers to link theological anxieties about the individual’s relationship to unseen truth with conceptual uncertainties about the power of literary fictions; to see that fiction, like religion, mediated between unknowable human interiority and the visible external world, and thus occupied an ambiguous, unstable position in relation to empirical phenomena.
The Edge of Satire
Authors: Robinson Peter
Published: September 2019

In this chapter, Peter Robinson identifies the edge where satire most sharply cuts and where, simultaneously, it may stop being satire. Responding to remarks of Jackson Bate’s on Johnson as a satirist manqué, an analysis of ‘On the Death of Dr. Robert Levet’ and other poems explores varieties of ways in which mortality in a Christian context displaces grounds for judgement, yet occasions criticism of literary pretension, the limits of friendship, and self-interest in the professional care of others. By contrast, a passage from Dryden’s ‘An Ode, on the Death of Mr. Henry Purcell’ rebukes the musician’s rivals so as to underline his loss to the world. Yet such a rebuke is edgeless to the extent that the rivalry it pinpoints has been nullified by the greater man’s demise. Thus, among relevant post-mortem and other effects here is the role death plays as a satirist of the impulse to satire.
Against the Experts
Authors: Bullard Paddy
Published: September 2019

This chapter looks at Jonathan Swift’s political satire, focusing on a crucial, seldom-discussed and newly relevant theme: his deep hostility towards specialists and experts. It argues that Swift and his allies understood expertise in terms of a broader anti-technical idea of statesmanship, one that also advocated ‘common sense’ as a positive model for political deliberation, and ‘wit’ as a model for discourse. Satire was a common medium for articulating this programme, often in terms that were themselves doubled and ironized. Swift and many of his associates deplored secrecy and innuendo in political life and, at the same time, appropriated them as modes for oppositional satire. They painted modern instrumental thinking and modern technocratic politics as dull and clumsy, while adopting the discourses of those experts parodically as ‘mock-arts’. It was the interrelations between this group of satirical themes and political topoi that gave them power and significance at the start of the eighteenth century.
‘Little Snarling Lapdogs’
Authors: Alliker Rabb Melinda
Published: September 2019

The domestic sphere increases as a subject for satire in the latter half of the eighteenth century. Literary histories assert satire’s decline after 1750 when creative energy shifts towards home, family, nature, individual subjectivity, and private feelings. But the apparent shift towards representations of domesticity does not simply displace but rather offers new opportunities to satire which insinuates itself into modes of writing almost as soon as they are formed and changes the shape they ultimately assume. In contrast to earlier satires on public figures, from royalty and ministers to prostitutes and Grub Street hacks, domestic satire often focuses on families and households, and on the precarious lives of dependants, servants, spinsters, illegitimate offspring, and other persons of socially ambiguous standing. Satire in an age of rising colonialism, economic competition, class struggle, and industrialization, must look beyond court and coffee-house into the parlour where satire has made itself at home.
Banter, Nonsense, and Irony
Authors: Rounce Adam
Published: September 2019

The Nonsense Club was a confederacy of writers who gathered around the polemical satirist Charles Churchill and his friend Robert Lloyd during the 1760s. Churchill was celebrated as an opposition polemicist, but other members of the Club—including Lloyd, George Colman, Bonnell Thornton, and William Cowper—adopt a less direct, often self-conscious satiric mode, marked by a nonchalant awareness of their work’s ultimate lack of effect. This results in an odd mix of outspoken critique, bracing satiric barbs, almost affectionate parody, and incidental, and ad hoc considerations of the purpose of writing itself. The present account offers a survey of the Club’s poetic satire: its attitude towards contemporary poetry, most notable in satires and burlesques; the small but clear originality in the work of Lloyd; and the satire of Churchill, the most immediately consequential poet to emerge from the group.
Legal Constraints, Libellous Evasions
Authors: Hone Joseph
Published: September 2019

This chapter considers the relationship between satire and the law during the eighteenth century. After the lapse of pre-publication licensing in 1695, satirists remained subject to the common law of libel (including seditious libel, blasphemous libel, and criminal libel) and to treason laws. Satirists and publishers used various strategies to evade prosecution under those laws: most notably anonymous publication (in print or in manuscript) and creative forms of ambiguity. This chapter surveys examples of those strategies in some famous and lesser known texts, before considering the introduction of the new Licensing Act in 1737, which restricted satire on the stage. Libel prosecutions continued even while the trend for hard-hitting lampoons faded out after the 1750s, but predominantly as a means of prosecuting political troublemakers.
Foxite Satire
Authors: Jones Robert W.
Published: September 2019

The Foxites were both affable and scurrilous; resolute opponents of an encroaching executive, they were equally determined in their pursuit of pleasure. They took particular delight in satire, drawing inspiration from Pope and Churchill, while retaining a thoroughly Whiggish admiration for Milton. Poetry in a sense provided a consolation for a lack of political power after George III ousted them from office in 1784. This essay examines the literary works of the Foxites’ best writers—Sheridan, Tickell, and Richardson. Their diverse and innovative work, much of it written and published collectively, intervened in both political and cultural controversies, from the contested Westminster election to the appointment of Thomas Warton as poet laureate. Personal abuse is heaped on William Pitt and his ministers, all of whom are reviled as inept, effeminate, and insinuating. But there is fun too at the expense of modish literary forms as well as the ponderous nature of parliamentary procedures.
Describing Eighteenth-Century British Satire
Authors: Bullard Paddy
Published: September 2019

This introductory chapter looks at the problem of how we should describe eighteenth-century satire, and considers how to place it historically in the British eighteenth century. It gathers key literary extracts and anecdotes from the period, statements in which different discussions of satire intersect with larger ideas about the period’s culture and society. The chapter is organized into three sections. The first looks at satirical commonalities, including the uses of satire in associational life, the body of commonplace critical opinion about its function, and its connection with emerging constructions of British nationhood. The second turns to literary satire’s material forms, looking for patterns in the way it was consumed by readers of printed books. The third moves on from these generalized contexts to examine some of satire’s personal, particular implications, including the question of whether satire should always be general, whether it could avoid referring to individuals.
Mary as Intercessor in Byzantine Theology
Authors: Neil Bronwen
Published: September 2019

Mary’s intercessory role appeared in the early Byzantine church in the sixth century, if not earlier, and popular belief in her power to aid sinners, even after death, only increased in the Middle Byzantine centuries, following broader trends in the literature and art of that period. These texts and images from the Eastern churches of Constantinople, Asia Minor, Egypt, Georgia, and Syria reveal a growth in affective piety, which highlighted Mary’s motherhood and compassion, making her a natural object for personal devotion. Mary, the human mother of God, was an accessible figure whose very accessibility made her uniquely placed to intercede between sinful believers and God and his son, Jesus Christ. The evidence presented here for the development of affective piety in the Byzantine cult of Mary as intercessor reveals that Byzantine beliefs and practices prefigured the same trend in the medieval West by several centuries.
Mary and Modernity
Authors: Spretnak Charlene
Published: September 2019

Because the Reformation was unfavourably disposed toward expressions of the cosmological, mystical, symbolic, and aesthetic dimensions of the Virgin Mary’s spiritual presence, and because secular versions of several concepts in the Reformation became central to emergent modernity, the work of modernizing the Catholic Church at Vatican II resulted in streamlining Mary’s presence and meaning in favour of a more literal, objective, and strictly text-based version, which is simultaneously more Protestant and more modern. In the decades since Vatican II, however, the modern, mechanistic worldview has been dislodged by discoveries in physics and biology indicating that physical reality, the Creation, is composed entirely of dynamic interrelatedness. This perception also informs the Incarnation, the Resurrection, Redemption, transubstantiation, and the full spiritual presence of Mary with its mystical and cosmological dimensions. Perhaps the rigid dividing lines at Vatican II will evolve into new possibilities in the twenty-first century regarding Mary and modernity.
Introduction
Authors: Maunder Chris
Published: September 2019

Mary is important in Christianity and Islam. Orthodox and Catholic Christianity can be argued to be intrinsically Marian. Theological reflection on Mary draws its logic primarily from the bringing together of the Prologue of John’s Gospel, as a Christian restatement of the creation in Genesis, with the first two chapters of Luke. Then Mary as an historical figure in the heritage of Israel is taken up into an eternal and cosmic space in which she participates in the events of redemption as the new Eve. The relationship between Christ and Mary leads to important debates in Christian traditions, and there are of course issues that arise for a modern gender analysis. The introduction moves on to doctrines of Mary, relationships between the denominations, and both ecclesiastical and popular devotion/veneration. It refers to each of the contributors of the book and shows how they interrelate in the volume as a whole.
The Annunciation from Luke to the Enlightenment
Authors: Waller Gary
Published: September 2019

This chapter provides a cultural rather than a theological reading of the Annunciation story, locating it historically from its beginnings in Luke to the pre-Enlightenment, and then, by interrogating that history, speculating about why for a millennium and a half (and beyond), the Gospel’s story of Gabriel’s appearance to Mary (Luke 1: 26–38) has had such a powerful hold over the Western imagination. The early modern period saw the discovery of multiple versions of the Annunciation story, and from Ersamus onwards, the emergence of critical history calling into question the historicity of the Gospel accounts.
Promoting Participation in Physical Activity and Exercise Among People Living with Chronic Pain: A Qualitative Study of Strategies Used by People with Pain and Their Recommendations for Health Care Providers
Authors: Vader Kyle , Patel Rupa , Doulas Tom , Miller Jordan
Published: September 2019

Objective

To explore strategies used by people living with chronic pain when participating in physical activity and exercise and their recommendations for health care providers when promoting participation in physical activity and exercise.

Design

Interpretive description qualitative study.

Setting

Participants were recruited from primary care sites and a hospital-based chronic pain clinic in Kingston, Ontario, Canada.

Subjects

Adults (>18 years of age) who self-identified as experiencing chronic pain (three months’ duration) were interviewed.

Methods

In-depth semistructured interviews were conducted with participants. Interviews were audio-recorded, transcribed verbatim, and reviewed for accuracy by the interviewer. Transcripts were analyzed using thematic analysis. Peer debriefing, reflexivity, and multiple in-person meetings were used to establish trustworthiness.

Results

Sixteen adults (five men, 11 women) with a median age of 53 years were interviewed. Strategies used by people living with chronic pain to participate in physical activity and exercise included 1) finding the motivation, 2) setting up for success, 3) leveraging social support, and 4) managing pain and discomfort during activity. Recommendations for health care providers when promoting participation in physical activity and exercise for people living with chronic pain included 1) the importance of listening, 2) providing tailored advice, 3) being supportive, and 4) making physical activity and exercise programming accessible.

Conclusions

People living with chronic pain reported using multiple strategies to participate in physical activity and exercise. Recommendations for health care providers centered on the importance of listening and taking a supportive approach when promoting engagement in physical activity and exercise for this population.