bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ICE metadata and the study of Hong Kong English
Authors: HANSEN BEKE 
Published: October 2017

ABSTRACTStudies of L1 varieties of English have shown that the modal domain has been reorganised over time. In particular the frequency of the core modal verb must has decreased, while the frequency of the semi‐modal verb have to has increased. As an area of ongoing change in L1 varieties, the modal and semi‐modal verbs have also attracted the interest of linguists working in the field of L2 varieties. However, the virtual absence of diachronic corpora for most ESL varieties presents a challenge for this area. This paper meets this challenge by exploring the potential of the neglected ICE metadata for bridging the diachronic gap in world Englishes. Information from the ICE‐Hong Kong (ICE‐HK) metadata is used to construct an apparent‐time scenario of the use of must, have to and (have) got to in the spoken section of ICE‐HK.
The impact of menstrual phase on brachial artery flow‐mediated dilatation during handgrip exercise in healthy premenopausal women
Authors: D'Urzo Katrina A. , King Trevor J. , Williams Jennifer S. , Silvester Morgan D. , Pyke Kyra E. 
Published: October 2017

New Findings
What is the central question of this study?
The aim of this study was to determine the influence of menstrual phase on flow‐mediated dilatation in response to sustained, exercise‐induced increases in shear stress.

What is the main finding and its importance?
We showed, for the first time, that in healthy, premenopausal women the flow‐mediated dilatation stimulated by exercise‐induced increases in shear stress did not fluctuate across two phases of the menstrual cycle, despite significant fluctuations in oestrogen. This suggests that endothelial function is not consistently augmented in the high‐oestrogen phase.

Flow‐mediated dilatation (FMD) in response to a sustained shear‐stress stimulus (e.g. via handgrip exercise; HGEX) is emerging as a useful tool for assessing endothelial function; however, the impact of menstrual phase on HGEX‐FMD is unknown. The purpose of this study was to determine whether HGEX‐FMD fluctuates with cyclical changes in oestrogen concentrations over two discrete phases (low and high oestrogen) of the menstrual cycle. Brachial artery (BA) diameter and blood velocity were assessed with two‐dimesional and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = BA blood velocity/BA diameter). Participants (12 healthy, regularly cycling women, 21 ± 2 years of age) completed two experimental visits: (i) low oestrogen (early follicular, EF); and (ii) high oestrogen (late follicular, LF). Reactive hyperaemia‐stimulated FMD (RH‐FMD) and HGEX‐FMD (6 min of handgrip exercise) were assessed during each visit. Results are mean values ± SD. Oestrogen increased from the EF to LF phase (EF, 33 ± 9 pg ml−1; LF, 161 ± 113 pg ml−1, P = 0.003). However, neither the SR stimuli (HGEX, P = 0.501; RH, P = 0.173) nor the FMD responses differed between phases (EF versus LF: HGEX‐FMD, 4.8 ± 2.8 versus 4.6 ± 2.2%, P = 0.601; RH‐FMD, 7.9 ± 4.3 versus 6.4 ± 3.1%, P = 0.071). These results extend existing RH‐FMD findings indicating that not all women experience fluctuations in FMD with the menstrual cycle. Further research is needed to investigate the mechanisms that underlie variability in the impact of menstrual phase on FMD.
Time, touch and temperature affect perceived finger position and ownership in the grasp illusion
Authors: Héroux Martin E. , Bayle Nicolas , Butler Annie A. , Gandevia Simon C. 
Published: October 2017

Key points
The brain's internal model of the body and the sense of body ownership are fundamental to interaction with the world.
It is thought that temporally congruent, repetitive multisensory stimuli are required to elicit a sense of body ownership.
Here we investigate the ability of static cutaneous stimuli – passively grasping an artificial finger – to induce body ownership and alter perceived body position; we also investigate how physical characteristics of grasped objects alter these senses.
We show that static cutaneous stimuli can alter perceived body position and induce an illusion of ownership and also that signals of temperature, texture and shape of grasped finger‐sized objects influence body ownership.
Thus, these aspects of human proprioception can be altered by a single sustained sensory stimulus and by the physical characteristics of held objects.
AbstractPerceived body position and ownership are fundamental to our ability to sense and interact with the world. Previous work indicates that temporally congruent, repetitive multisensory stimuli are needed to alter the sense of body ownership. In the present study 30 subjects passively grasped an artificial rubber finger with their left index and thumb while their right index finger, located 12 cm below, was lightly clamped. Fingers with varied physical characteristics were also passively grasped to determine how these characteristics influenced perceived body position and ownership. Subjects immediately felt their hands to be 5.3 cm [3.4–7.3] (mean [95%CI]) closer, a feeling that remained after 3 min (6.0 cm [4.5–7.5]). By the end of the trial, perceived ownership increased by 1.2 [0.6–1.9] points on a 7‐point Likert scale, with the group average moving from ‘neither agree or disagree’ at the start to ‘somewhat agree’ at the end. Compared to grasping a control rubber finger, grasping a cold, rough, oddly shaped or rectangular shaped finger‐like object reduced perceived ownership. These results provide new insights into the role of cutaneous sensory receptors in defining these aspects of proprioception, and the speed with which these effects occur. Static touch rapidly induces large, sustained changes in perceived body position and prolonged exposure to these cutaneous inputs, alone, can induce a sense of body ownership. Also, certain physical characteristics of grasped objects influence the sense of body ownership.
Control Simulation of Hydraulic Adjustment System
Authors: Chiang Yu-Lun , Chuang Jen-Chen , Tu Jia-Ying 
Published: October 2017

Hydraulic actuation systems are widely applied in the modern industry, such as robots, excavators, vehicle suspension systems, machine tools, and testing of structural systems, because hydraulic actuation systems are able to provide with large loading capacity. However, the design parameters and control techniques related to temperature, flow volume, flow resistance, etc., affect the stable performance of hydraulic pressure and need to be concerned with. In addition, while an unexpected external loading is applied, which makes a reaction force to the hydraulic oil and results in pressure variations, advanced real-time control techniques is required, in order to maintain a high-level stability and accuracy of the output pressure. To this end, a hydraulic power system is developed in this work, which installs two proportional valves for real-time adjustment of hydraulic pressure.
In this paper, the performance compensation of hydraulic pressure involves two steps of control development; the first step is to establish the mathematical model of the hydraulic adjustment system, and the second step is to simulate the pressure response of hydraulic adjustment system with controller design. In this first step, real-time dSPACE control system is utilized to implement identification work, for the purpose of establishing a multi-input/multi-output (MIMO) dynamic model of the active hydraulic adjustment system. Then, based on the dynamic model, the second step develops a feedforward-feedback and a PID controller for the active hydraulic adjustment system; the dynamic responses and control performance are verified via numerical simulation studies.
In Vitro
Human Onychopharmacokinetic and Pharmacodynamic Analyses of ME1111, a New Topical Agent for Onychomycosis
Authors: Kubota-Ishida Natsuki , Takei-Masuda Naomi , Kaneda Kaori , Nagira Yu , Chikada Tsubasa , Nomoto Masahiro , Tabata Yuji , Takahata Sho , Maebashi Kazunori , Hui Xiaoying , Maibach Howard I. 
Published: October 2017

ABSTRACT

ME1111 is a novel antifungal agent currently under clinical development as a topical onychomycosis treatment. A major challenge in the application of topical onychomycotics is penetration and dissemination of antifungal agent into the infected nail plate and bed. In this study, pharmacokinetic/pharmacodynamic parameters of ME1111 that potentially correlate with clinical efficacy were compared with those of marketed topical onychomycosis antifungal agents: efinaconazole, tavaborole, ciclopirox, and amorolfine. An ME1111 solution and other launched topical formulations were applied to an
in vitro
dose model for 14 days based on their clinical dose and administration. Drug concentrations in the deep layer of the nail and within the cotton pads beneath the nails were measured using liquid chromatography-tandem mass spectrometry. Concentrations of ME1111 in the nail and cotton pads were much higher than those of efinaconazole, ciclopirox, and amorolfine. Free drug concentrations of ME1111 in deep nail layers and cotton pads were orders of magnitude higher than the MIC
90
value against
Trichophyton rubrum
(
n
= 30). Unlike other drugs, the
in vitro
antifungal activity of ME1111 was not affected by 5% human keratin and under a mild acidic condition (pH 5.0). The
in vitro
antidermatophytic efficacy coefficients (ratio of free drug concentration to MIC
90
s against
T. rubrum
) of ME1111, as measured in deep nail layers, were significantly higher than those of efinaconazole, tavaborole, ciclopirox, and amorolfine (
P
< 0.05). This suggests that ME1111 has excellent permeation of human nails and, consequently, the potential to be an effective topical onychomycosis treatment.
Chitinase Induction Prior to Caspofungin Treatment of Experimental Invasive Aspergillosis in Neutropenic Rats Does Not Enhance Survival
Authors: Refos Jeannine M. , Vonk Alieke G. , ten Kate Marian T. , Verbrugh Henri A. , Bakker-Woudenberg Irma A. J. M. , van de Sande Wendy W. J. 
Published: October 2017

ABSTRACT

Host chitinases, chitotriosidase and acidic mammalian chitinase (AMCase), improved the antifungal activity of caspofungin (CAS) against
Aspergillus fumigatus in vitro
. These chitinases are not constitutively expressed in the lung. Here, we investigated whether chitosan derivatives were able to induce chitinase activity in the lungs of neutropenic rats and, if so, whether these chitinases were able to prolong survival of rats with invasive pulmonary aspergillosis (IPA) or of rats with IPA and treated with CAS. An oligosaccharide-lactate chitosan (OLC) derivative was instilled in the left lung of neutropenic rats to induce chitotriosidase and AMCase activities. Rats instilled with OLC or with phosphate-buffered saline (PBS) were subsequently infected with
A. fumigatus
and then treated with suboptimal doses of CAS. Survival, histopathology, and galactomannan indexes were determined. Instillation of OLC resulted in chitotriosidase and AMCase activities. However, instillation of OLC did not prolong rat survival when rats were subsequently challenged with
A. fumigatus
. In 5 of 7 rats instilled with OLC, the fungal foci in the lungs were smaller than those in rats instilled with PBS. Instillation of OLC did not significantly enhance the survival of neutropenic rats challenged with
A. fumigatus
and treated with a suboptimal dosage of CAS. Chitotriosidase and AMCase activities can be induced with OLC, but the presence of active chitinases in the lung did not prevent the development of IPA or significantly enhance the therapeutic outcome of CAS treatment.
Mutations at the Ribosomal S10 Gene in Clinical Strains of Staphylococcus aureus with Reduced Susceptibility to Tigecycline
Authors: Argudín M. Angeles , Roisin S. , Dodémont M. , Nonhoff C. , Deplano A. , Denis O. 
Published: October 2017

ABSTRACT

Mutations on the tip of the extended loop of the ribosomal S10 protein have been associated to tigecycline (TGC) resistance in passaged mutants of different bacteria species. This study described the first two clinical TGC-resistant
Staphylococcus aureus
isolates with these mutations. One strain (TGC MIC = 2 mg/liter) had a 12-nucleotide deletion affecting residues 56 to 59 (HKYK) of the S10 protein. The second strain (TGC MIC = 1 mg/liter) had amino acid substitutions (K57M and Y58F) previously described in
S. aureus
passaged mutants.
Antifungal Susceptibility of Emerging Dimorphic Pathogens in the Family Ajellomycetaceae
Authors: Dukik Karolina , Al-Hatmi Abdullah M. S. , Curfs-Breuker Ilse , Faro Dirk , de Hoog Sybren , Meis Jacques F. 
Published: October 2017

ABSTRACT

The
in vitro
susceptibilities of 24 molecularly identified dimorphic fungi belonging to the genera
Adiaspiromyces
,
Blastomyces
, and
Emergomyces
within the family
Ajellomycetaceae
were tested against 8 standard antifungal agents using CLSI document M38-A2. Amphotericin B and posaconazole had the lowest geometric mean MICs (<0.05 μg/ml) followed by itraconazole (<0.07 μg/ml), voriconazole (<0.15 μg/ml), and isavuconazole (<0.42 μg/ml) while fluconazole was not active. Micafungin demonstrated good
in vitro
antifungal activity against
Emergomyces
(geometric mean minimum effective concentration [GM MEC] 0.1 μg/ml) and
Blastomyces
(GM MEC <0.017 μg/ml).
In Vitro
Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae
Authors: Hackel Meredith A. , Lomovskaya Olga , Dudley Michael N. , Karlowsky James A. , Sahm Daniel F. 
Published: October 2017

ABSTRACT

Vaborbactam (formerly RPX7009) is a novel inhibitor of serine β-lactamases, including Ambler class A carbapenemases, such as KPCs. The current study evaluated the
in vitro
activity of the combination agent meropenem-vaborbactam against a global collection of 991 isolates of KPC-positive
Enterobacteriaceae
collected in 2014 and 2015 using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. The MIC
90
of meropenem (when tested with a fixed concentration of 8 μg/ml of vaborbactam) for isolates of KPC-positive
Enterobacteriaceae
was 1 μg/ml, and MIC values ranged from ≤0.03 to >32 μg/ml; 99.0% (981/991) of isolates had meropenem-vaborbactam MICs of ≤4 μg/ml, the U.S. FDA-approved MIC breakpoint for susceptibility to meropenem-vaborbactam (Vabomere). Vaborbactam lowered the meropenem MIC
50
from 32 to 0.06 μg/ml and the MIC
90
from >32 to 1 μg/ml. There were no differences in the activity of meropenem-vaborbactam when the isolates were stratified by KPC variant type. We conclude that meropenem-vaborbactam demonstrates potent
in vitro
activity against a worldwide collection of clinical isolates of KPC-positive
Enterobacteriaceae
collected in 2014 and 2015.
Molecular Pathogenesis of Chlamydia Disease Complications: Epithelial-Mesenchymal Transition and Fibrosis
Authors: Igietseme Joseph U. , Omosun Yusuf , Nagy Tamas , Stuchlik Olga , Reed Matthew S. , He Qing , Partin James , Joseph Kahaliah , Ellerson Debra , George Zenas , Goldstein Jason , Eko Francis O. , Bandea Claudiu , Pohl Jan , Black Carolyn M. 
Published: October 2017

ABSTRACT
The reproductive system complications of genital chlamydial infection include fallopian tube fibrosis and tubal factor infertility. However, the molecular pathogenesis of these complications remains poorly understood. The induction of pathogenic epithelial-mesenchymal transition (EMT) through microRNA (miRNA) dysregulation was recently proposed as the pathogenic basis of chlamydial complications. Focusing on fibrogenesis, we investigated the hypothesis that chlamydia-induced fibrosis is caused by EMT-driven generation of myofibroblasts, the effector cells of fibrosis that produce excessive extracellular matrix (ECM) proteins. The results revealed that the targets of a major category of altered miRNAs during chlamydial infection are key components of the pathophysiological process of fibrogenesis; these target molecules include collagen types I, III, and IV, transforming growth factor β (TGF-β), TGF-β receptor 1 (TGF-βR1), connective tissue growth factor (CTGF), E-cadherin, SRY-box 7 (SOX7), and NFAT (nuclear factor of activated T cells) kinase dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1a (Dyrk1a). Chlamydial induction of EMT resulted in the generation of α-smooth muscle actin (α-SMA)-positive myofibroblasts that produced ECM proteins, including collagen types I and III and fibronectin. Furthermore, the inhibition of EMT prevented the generation of myofibroblasts and production of ECM proteins during chlamydial infection. These findings may provide useful avenues for targeting EMT or specific components of the EMT pathways as a therapeutic intervention strategy to prevent chlamydia-related complications.
What Is a Host? Attributes of Individual Susceptibility
Authors: Casadevall Arturo , Pirofski Liise-anne 
Published: October 2017

ABSTRACTIn every epidemic some individuals become sick and some may die, whereas others recover from illness and still others show no signs or symptoms of disease. These differences highlight a fundamental question of microbial pathogenesis: why are some individuals susceptible to infectious diseases while others who acquire the same microbe remain well? For most of human history, the answer assumed the hand of providence. With the advent of the germ theory of disease, the focus on disease causality became the microbe, but this did not explain how there can be different outcomes of infection in different individuals with the same microbe. Here we examine the attributes of susceptibility in the context of the “damage-response framework” of microbial pathogenesis. We identify 11 attributes that, although not independent, are sufficiently distinct to be considered separately: microbiome, inoculum, sex, temperature, environment, age, chance, history, immunity, nutrition, and genetics. We use the first letter of each to create the mnemonic MISTEACHING, underscoring the need for caution in accepting dogma and attributing disease causality to any single factor. For both populations and individuals, variations in the attributes that assemble into MISTEACHING can create an enormity of combinations that can in turn translate into different outcomes of host-microbe encounters. Combinatorial diversity among the 11 attributes makes identifying “signatures” of susceptibility possible. However, with their inevitable uncertainties and propensity to change, there may still be a low likelihood for prediction with regard to individual host-microbe interactions, although probabilistic prediction may be possible.
Identification of Parameters of Host Cell Vulnerability during Salmonella Infection by Quantitative Image Analysis and Modeling
Authors: Voznica Jakub , Gardella Christophe , Belotserkovsky Ilia , Dufour Alexandre , Enninga Jost , Stévenin Virginie 
Published: October 2017

ABSTRACT

Salmonella
targets and enters epithelial cells at permissive entry sites: some cells are more likely to be infected than others. However, the parameters that lead to host cell heterogeneity are not known. Here, we quantitatively characterized host cell vulnerability to
Salmonella
infection based on imaged parameters. We performed successive infections of the same host cell population followed by automated high-throughput microscopy and observed that infected cells have a higher probability of being reinfected. Establishing a predictive model, we identified two combined origins of host cell vulnerability: pathogen-induced cellular vulnerability emerging from
Salmonella
uptake and persisting at later stages of the infection and host cell-inherent vulnerability. We linked the host cell-inherent vulnerability with its morphological attributes, such as local cell crowding, and with host cell cholesterol content. This showed that the probability of
Salmonella
infection success can be forecast from morphological or molecular host cell parameters.
Visualizing Bacterial Colony Morphologies Using Time-Lapse Imaging Chamber MOCHA
Authors: Peñil Cobo Maria , Libro Silvia , Marechal Nils , D'Entremont David , Peñil Cobo David , Berkmen Mehmet 
Published: October 2017

ABSTRACT

Capturing microbial growth on a macroscopic scale is of great importance to further our understanding of microbial life. However, methods for imaging microbial life on a scale of millimeters to centimeters are often limited by designs that have poor environmental control, resulting in dehydration of the agar plate within just a few days. Here, we created MOCHA (
m
icr
o
bial
cha
mber), a simple but effective chamber that allows users to study microbial growth for extended periods (weeks) in a stable environment. Agar hydration is maintained with a double-decker design, in which two glass petri dishes are connected by a wick, allowing the lower plate to keep the upper plate hydrated. This flexible chamber allows the observation of a variety of microbiological phenomena, such as the growth and development of single bacterial and fungal colonies, interspecies interactions, swarming motility, and pellicle formation.

IMPORTANCE
Detailed study of microbial life on the colony scale of millimeters to centimeters has been lagging considerably behind microscopic inspection of microbes. One major reason for this is the lack of inexpensive instrumentation that can reproducibly capture images in a controlled environment. In this study, we present the design and use of a unique chamber that was used to produce several time-lapse movies that aimed to capture the diversity of microbial colony phenotypes over long periods.
New Kid on the Block: LmbU Expands the Repertoire of Specialized Metabolic Regulators in Streptomyces
Authors: Ju Kou-San , Zhang Xiafei , Elliot Marie A. 
Published: October 2017

ABSTRACTStreptomyceshas an extensive natural product repertoire, including most of the naturally derived antibiotics. Understanding the control of natural product biosynthesis is central to antibiotic discovery and production optimization. Here, Hou et al. (J. Bacteriol. 200:00447-17, 2018,https://doi.org/10.1128/JB.00447-17) report the identification and characterization of a novel regulator—LmbU—that functions primarily as an activator of lincomycin production inStreptomyces lincolnensis. Importantly, members of this new regulator family are associated with natural product biosynthetic clusters throughout the streptomycetes and their actinomycete relatives.