bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells
Authors: Nakamura Muneaki , Srinivasan Prashanth , Chavez Michael , Carter Matthew A. , Dominguez Antonia A. , La Russa Marie , Lau Matthew B. , Abbott Timothy R. , Xu Xiaoshu , Zhao Dehua , Gao Yuchen , Kipniss Nathan H. , Smolke Christina D. , Bondy-Denomy Joseph , Qi Lei S. 
Published: January 2019

AbstractRepurposed CRISPR-Cas molecules provide a useful tool set for broad applications of genomic editing and regulation of gene expression in prokaryotes and eukaryotes. Recent discovery of phage-derived proteins, anti-CRISPRs, which serve to abrogate natural CRISPR anti-phage activity, potentially expands the ability to build synthetic CRISPR-mediated circuits. Here, we characterize a panel of anti-CRISPR molecules for expanded applications to counteract CRISPR-mediated gene activation and repression of reporter and endogenous genes in various cell types. We demonstrate that cells pre-engineered with anti-CRISPR molecules become resistant to gene editing, thus providing a means to generate “write-protected” cells that prevent future gene editing. We further show that anti-CRISPRs can be used to control CRISPR-based gene regulation circuits, including implementation of a pulse generator circuit in mammalian cells. Our work suggests that anti-CRISPR proteins should serve as widely applicable tools for synthetic systems regulating the behavior of eukaryotic cells.
A macrophage-based screen identifies antibacterial compounds selective for intracellular Salmonella Typhimurium
Authors: Ellis Michael J. , Tsai Caressa N. , Johnson Jarrod W. , French Shawn , Elhenawy Wael , Porwollik Steffen , Andrews-Polymenis Helene , McClelland Michael , Magolan Jakob , Coombes Brian K. , Brown Eric D. 
Published: January 2019

AbstractSalmonella Typhimurium (S. Tm) establishes systemic infection in susceptible hosts by evading the innate immune response and replicating within host phagocytes. Here, we sought to identify inhibitors of intracellular S. Tm replication by conducting parallel chemical screens against S. Tm growing in macrophage-mimicking media and within macrophages. We identify several compounds that inhibit Salmonella growth in the intracellular environment and in acidic, ion-limited media. We report on the antimicrobial activity of the psychoactive drug metergoline, which is specific against intracellular S. Tm. Screening an S. Tm deletion library in the presence of metergoline reveals hypersensitization of outer membrane mutants to metergoline activity. Metergoline disrupts the proton motive force at the bacterial cytoplasmic membrane and extends animal survival during a systemic S. Tm infection. This work highlights the predictive nature of intracellular screens for in vivo efficacy, and identifies metergoline as a novel antimicrobial active against Salmonella.
Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion
Authors: Vergari Elisa , Knudsen Jakob G. , Ramracheya Reshma , Salehi Albert , Zhang Quan , Adam Julie , Asterholm Ingrid Wernstedt , Benrick Anna , Briant Linford J. B. , Chibalina Margarita V. , Gribble Fiona M. , Hamilton Alexander , Hastoy Benoit , Reimann Frank , Rorsman Nils J. G. , Spiliotis Ioannis I. , Tarasov Andrei , Wu Yanling , Ashcroft Frances M. , Rorsman Patrik 
Published: January 2019

AbstractHypoglycaemia (low plasma glucose) is a serious and potentially fatal complication of insulin-treated diabetes. In healthy individuals, hypoglycaemia triggers glucagon secretion, which restores normal plasma glucose levels by stimulation of hepatic glucose production. This counterregulatory mechanism is impaired in diabetes. Here we show in mice that therapeutic concentrations of insulin inhibit glucagon secretion by an indirect (paracrine) mechanism mediated by stimulation of intra-islet somatostatin release. Insulin’s capacity to inhibit glucagon secretion is lost following genetic ablation of insulin receptors in the somatostatin-secreting δ-cells, when insulin-induced somatostatin secretion is suppressed by dapagliflozin (an inhibitor of sodium-glucose co-tranporter-2; SGLT2) or when the action of secreted somatostatin is prevented by somatostatin receptor (SSTR) antagonists. Administration of these compounds in vivo antagonises insulin’s hypoglycaemic effect. We extend these data to isolated human islets. We propose that SSTR or SGLT2 antagonists should be considered as adjuncts to insulin in diabetes therapy.
Controlling the fluorescence and room-temperature phosphorescence behaviour of carbon nanodots with inorganic crystalline nanocomposites
Authors: Green David C. , Holden Mark A. , Levenstein Mark A. , Zhang Shuheng , Johnson Benjamin R. G. , Gala de Pablo Julia , Ward Andrew , Botchway Stanley W. , Meldrum Fiona C. 
Published: January 2019

AbstractThere is a significant drive to identify alternative materials that exhibit room temperature phosphorescence for technologies including bio-imaging, photodynamic therapy and organic light-emitting diodes. Ideally, these materials should be non-toxic and cheap, and it will be possible to control their photoluminescent properties. This was achieved here by embedding carbon nanodots within crystalline particles of alkaline earth carbonates, sulphates and oxalates. The resultant nanocomposites are luminescent and exhibit a bright, sub-second lifetime afterglow. Importantly, the excited state lifetimes, and steady-state and afterglow colours can all be systematically controlled by varying the cations and anions in the host inorganic phase, due to the influence of the cation size and material density on emissive and non-emissive electronic transitions. This simple strategy provides a flexible route for generating materials with specific, phosphorescent properties and is an exciting alternative to approaches relying on the synthesis of custom-made luminescent organic molecules.
A new carbon phase with direct bandgap and high carrier mobility as electron transport material for perovskite solar cells
Authors: Sun Ping-Ping , Bai Lichun , Kripalani Devesh R. , Zhou Kun 
Published: January 2019

AbstractRapid development of perovskite solar cells is challenged by the fact that current semiconductors hardly act as efficient electron transport materials that can feature both high electron mobility and a well-matched energy level to that of the perovskite. Here we show that T-carbon, a newly emerging carbon allotrope, could be an ideal candidate to meet this challenge. By using first-principles calculations and deformation potential theory, it is found that T-carbon is a semiconductor with a direct bandgap of 2.273 eV, and the energy level in the conduction band is lower than that of perovskite by 0.5 eV, showing a larger force of electron injection. Moreover, the calculated electron mobility can reach up to 2.36 × 103 cm2 s–1 V–1, superior to conventional electron transport materials such as TiO2, ZnO and SnO2, which will facilitate more efficient electron separation and more rapid diffusion away from their locus of generation within the perovskite absorbers. Furthermore, the bandgap of T-carbon is highly sensitive to strain, thus providing a convenient method to tune the carrier transport capability. Overall, T-carbon satisfies the requirements for a potential efficient electron transport material and could therefore be capable of accelerating the development of perovskite solar cells.
Cysteine Disulfides (Cys-ss-X) as Sensitive Plasma Biomarkers of Oxidative Stress
Authors: Fu Xiaoyun , Cate Shelby A. , Dominguez Melissa , Osborn Warren , Özpolat Tahsin , Konkle Barbara A. , Chen Junmei , López José A. 
Published: January 2019

AbstractWe developed a high-throughput mass spectrometry–based method to simultaneously quantify numerous small-molecule thiols and disulfides in blood plasma. Application of this assay to analyze plasma from patients with known oxidative stress (sickle cell disease and sepsis) and from a patient with sickle cell disease treated with the antioxidant N-acetylcysteine suggests that cysteine disulfides, in particular protein-bound cysteine, serve as sensitive plasma biomarkers for the extent of oxidative stress and effectiveness of antioxidant treatment.
The bile salt glycocholate induces global changes in gene and protein expression and activates virulence in enterotoxigenic Escherichia coli
Authors: Joffre Enrique , Nicklasson Matilda , Álvarez-Carretero Sandra , Xiao Xue , Sun Lei , Nookaew Intawat , Zhu Baoli , Sjöling Åsa 
Published: January 2019

AbstractPathogenic bacteria use specific host factors to modulate virulence and stress responses during infection. We found previously that the host factor bile and the bile component glyco-conjugated cholate (NaGCH, sodium glycocholate) upregulate the colonization factor CS5 in enterotoxigenic Escherichia coli (ETEC). To further understand the global regulatory effects of bile and NaGCH, we performed Illumina RNA-Seq and found that crude bile and NaGCH altered the expression of 61 genes in CS5 + CS6 ETEC isolates. The most striking finding was high induction of the CS5 operon (csfA-F), its putative transcription factor csvR, and the putative ETEC virulence factor cexE. iTRAQ-coupled LC-MS/MS proteomic analyses verified induction of the plasmid-borne virulence proteins CS5 and CexE and also showed that NaGCH affected the expression of bacterial membrane proteins. Furthermore, NaGCH induced bacteria to aggregate, increased their adherence to epithelial cells, and reduced their motility. Our results indicate that CS5 + CS6 ETEC use NaGCH present in the small intestine as a signal to initiate colonization of the epithelium.
A Novel Method for Automatic Identification of Breathing State
Authors: Niu Jinglong , Cai Maolin , Shi Yan , Ren Shuai , Xu Weiqing , Gao Wei , Luo Zujin , Reinhardt Joseph M. 
Published: January 2019

AbstractSputum deposition blocks the airways of patients and leads to blood oxygen desaturation. Medical staff must periodically check the breathing state of intubated patients. This process increases staff workload. In this paper, we describe a system designed to acquire respiratory sounds from intubated subjects, extract the audio features, and classify these sounds to detect the presence of sputum. Our method uses 13 features extracted from the time-frequency spectrum of the respiratory sounds. To test our system, 220 respiratory sound samples were collected. Half of the samples were collected from patients with sputum present, and the remainder were collected from patients with no sputum present. Testing was performed based on ten-fold cross-validation. In the ten-fold cross-validation experiment, the logistic classifier identified breath sounds with sputum present with a sensitivity of 93.36% and a specificity of 93.36%. The feature extraction and classification methods are useful and reliable for sputum detection. This approach differs from waveform research and can provide a better visualization of sputum conditions. The proposed system can be used in the ICU to inform medical staff when sputum is present in a patient’s trachea.
Predicting Hemodynamic Shock from Thermal Images using Machine Learning
Authors: Nagori Aditya , Dhingra Lovedeep Singh , Bhatnagar Ambika , Lodha Rakesh , Sethi Tavpritesh 
Published: January 2019

AbstractProactive detection of hemodynamic shock can prevent organ failure and save lives. Thermal imaging is a non-invasive, non-contact modality to capture body surface temperature with the potential to reveal underlying perfusion disturbance in shock. In this study, we automate early detection and prediction of shock using machine learning upon thermal images obtained in a pediatric intensive care unit of a tertiary care hospital. 539 images were recorded out of which 253 had concomitant measurement of continuous intra-arterial blood pressure, the gold standard for shock monitoring. Histogram of oriented gradient features were used for machine learning based region-of-interest segmentation that achieved 96% agreement with a human expert. The segmented center-to-periphery difference along with pulse rate was used in longitudinal prediction of shock at 0, 3, 6 and 12 hours using a generalized linear mixed-effects model. The model achieved a mean area under the receiver operating characteristic curve of 75% at 0 hours (classification), 77% at 3 hours (prediction) and 69% at 12 hours (prediction) respectively. Since hemodynamic shock associated with critical illness and infectious epidemics such as Dengue is often fatal, our model demonstrates an affordable, non-invasive, non-contact and tele-diagnostic decision support system for its reliable detection and prediction.
Cisplatin reacts with histone H1 and the adduct forms a ternary complex with DNA
Authors: Cheng Lanjun , Li Chan , Xi Zhaoyong , Wei Kaiju , Yuan Siming , Arnesano Fabio , Natile Giovanni , Liu Yangzhong 
Published: January 2019

Abstract
Cisplatin is an anticancer drug widely used in clinics; it induces the apoptosis of cancer cells by targeting DNA. However, its interaction with proteins has been found to be crucial in modulating the pre and post-target activity. Nuclear DNA is tightly assembled with histone proteins to form nucleosomes in chromatin; this can impede the drug to access DNA. On the other hand, the linker histone H1 is considered ‘the gate to nucleosomal DNA’ due to its exposed location and dynamic conformation; therefore, this protein can influence the platination of DNA. In this study, we performed a reaction of cisplatin with histone H1 and investigated the interaction of the H1/cisplatin adduct with DNA. The reactions were conducted on the N-terminal domains of H1.4 (sequence 1–90, H1N90) and H1.0 (sequence 1–7, H1N7). The results show that H1 readily reacts with cisplatin and generates bidentate and tridentate adducts, with methionine and glutamate residues as the preferential binding sites. Chromatographic and NMR analyses show that the platination rate of H1 is slightly higher than that of DNA and the platinated H1 can form H1–cisplatin–DNA ternary complexes. Interestingly, cisplatin is more prone to form H1–Pt–DNA ternary complexes than trans-oriented platinum agents. The formation of H1–cisplatin–DNA ternary complexes and their preference for cis- over trans-oriented platinum agents suggest an important role of histone H1 in the mechanism of action of cisplatin.
Application of UPFC in Fujian 500 kV power grid
Authors: Li Meng , Lin Zhangsui , Wu Wei , Lin Yi , Jiang Pengbo , Hu Zhenda , Ye Rong , Du Yi 
Published: January 2019

In order to release the capability restriction of the North–South transmission channels in the 500 kV power grid of Fujian Province, this article studies the application of unified power flow controller (UPFC) to improve the transmission capability under steady‐state security restriction with N −1 principle. On the basis of analysis of principle and structure of UPFC, a simplified equivalent model of UPFC is constructed and used in BPA simulation software. The optimal installation scheme and the minimal capacity required of UPFC are determined by comparing the results of power flow calculation in various schemes. The research result shows that the application of UPFC can effectively reduce the N −1 overload problem of the North–South transmission channels, and has a great economic advantage over the traditional solution. Finally, based on the technical and economic analysis, this study puts forward suggestions on the construction of UPFC in the Fujian 500 kV power grid.
Analysis on structural parameters and electrical performance of dc deep well grounding electrode
Authors: Teng Yun , Wen Xishan , Cai Hansheng , Jia Lei , Liu Gang , Hu Shangmao , Lu Hailiang 
Published: January 2019

Deep well‐grounding electrodes (DWGE) have advantage of smaller occupied area, and the number of sub‐ground electrodes is less than that of the vertical grounding electrodes, thus has a good development prospects. Here, the simulation model of the electrical parameters of the DWGEs is established, and the electrical performance of the same length DWGE and the horizontal grounding electrodes is compared. The influence of length and the cross‐sectional diameter on the electrical performance of electrodes is studied. The simulation results and analysis show that compared with the shallow buried horizontal grounding electrodes, the DWGEs have the performance of smaller ground resistance and lower maximum step voltage. By increasing the length of grounding electrodes, the ground resistance, the maximum dissipation current density, and step voltage decrease, the surface potential of the nearby area decreases. Increasing the cross‐sectional diameter to improve the electrical performance of electrodes is not obvious, except for the dissipation current density. It is suggested that the length of the DWGEs in the project should not exceed 1500 m and the diameter of the coke is less than 0.4 m.
Hydrothermal synthesis of novel Ni microflowers with enhanced ferromagnetic properties
Authors: Han Xinghua , Xu Chunju , Chen Huiyu 
Published: January 2019

Novel nickel microflowers assembled with many thin nanoplates were synthesised through a simple hydrothermal method using sodium hypophosphite as a green reducing reagent. Sodium tartrate served as a complexing reagent and cetyltrimethylammonium bromide (CTAB) was used as a surfactant. It was found that the amount of sodium hydroxide played a key role in determining both the shape and to further the self‐assembly process of nickel flowers. Such a flower‐like nickel microstructure shows a great enhancement of the ferromagnetic properties with a coercivity of 308.7 Oe, which may be ascribed to the distinctive two‐dimensional (2D) anisotropic structure of the nanoplates and the final hierarchically flower‐like shape. This work presents a preferred approach to fabricate high‐quality magnetic nickel microflowers which have potential applications in electrochemical devices, magnetic sensors, and catalytic agents.
Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth
Authors: Lorenzo Guillermo , Hughes Thomas J. R. , Dominguez-Frojan Pablo , Reali Alessandro , Gomez Hector 
Published: January 2019

Significance
Benign prostatic hyperplasia (BPH) is a common disease in aging men that causes the prostate to enlarge progressively. Men with larger prostates tend to harbor prostatic tumors with more favorable features. The underlying mechanisms that explain this interaction between BPH and prostate cancer (PCa) are largely unknown. Here, we propose that BPH may mechanically impede PCa growth by producing increasingly intense mechanical stresses in the prostate over time, which are known to slow down tumor dynamics. To explore this hypothesis, we ran a qualitative simulation study using an extension of our mathematical model of PCa growth including the mechanical deformation of the prostate under BPH and PCa. The proposed mechanism suggests relevant shifts in clinical management of PCa and BPH.
FAS and FASL polymorphisms and susceptibility to hepatitis B virus infection in Javanese individuals
Authors: Prasetyo A A , Agustin D A 
Published: January 2019

AbstractHepatitis B virus infection is still a major global health problem. The polymorphisms in FAS and FASL genes may involve with susceptibility to hepatitis B virus infection for Javanese. To investigate the association of FAS and FASL polymorphisms with the susceptibility to hepatitis B virus infection in Javanese individuals, blood samples with hepatitis B virus infection was subjected for polymerase chain reaction-restriction fragment length polymorphism to genotype the FAS-670 A/G and FASL -124A/G polymorphism status, respectively. The frequencies of G/G genotype and G allele of FAS gene in the hepatitis B virus-infected blood sample were higher than that of the healthy sample (OR 3.5, 95%CI: 1.658 - 7.390, p = 0.001 and OR 2.3, 95%CI: 1.352 - 3.779, p = 0.002, respectively). It is proposed that the hepatitis B virus infection outcome in Japanese individuals might be influenced by FAS-670 A/G polymorphism through alteration in apoptosis of hepatocytes.
Hypercorrection as a By-product of Education
Authors: Hubers Ferdy , Trompenaars Thijs , Collin Sebastian , De Schepper Kees , De Hoop Helen 
Published: January 2019

AbstractPrescriptive grammar rules are taught in education, generally to ban the use of certain frequently encountered constructions in everyday language. This may lead to hypercorrection, meaning that the prescribed form in one construction is extended to another one in which it is in fact prohibited by prescriptive grammar. We discuss two such cases in Dutch: the hypercorrect use of the comparative particle dan ‘than’ in equative constructions, and the hypercorrect use of the accusative pronoun hen ‘them’ for a dative object. In two experiments, high school students of three educational levels were tested on their use of these hypercorrect forms (nexp1 = 162, nexp2 = 159). Our results indicate an overall large amount of hypercorrection across all levels of education, including pre-university level students who otherwise perform better in constructions targeted by prescriptive grammar rules. We conclude that while teaching prescriptive grammar rules to high school students seems to increase their use of correct forms in certain constructions, this comes at a cost of hypercorrection in others.
Translating the Jansenist Controversy in Britain and Ireland
Authors: Williams Mark R F 
Published: January 2019

Abstract
This article explores perceptions of Jansenism in Britain and Ireland in the latter half of the seventeenth century. Grounded in the theology of Cornelius Jansen, the Catholic bishop of Ypres, the wider Jansenist ‘movement’ was a controversial group of theologians, philosophers, clergy and nuns whose disputes with the papacy and French monarchy endured well into the eighteenth century. These centred on questions of divine grace, papal fallibility and even political dissent. In exploring the translation and reception of these ideas, this article foregrounds a moment in the late 1670s when the natural philosopher Robert Boyle and a group of like-minded Protestants attempted to incorporate Jansenist writings into a translation of the Bible into Irish. Enthusiasm for this was based on widely held perceptions that the Jansenists represented a more rational strain of Catholicism which anticipated a broader reform of Catholic Europe. The ensuing ‘Jansenist Preface’ was intended to help unify Christendom by bringing about a more rational religion among Ireland’s Catholics. The shock felt by Boyle and his collaborators upon actually reading Jansenist works, and the reappraisal this engendered, provides the foundation for a wider exploration of how ideas and representations of the Jansenist controversy moved, were translated, and subsequently engaged with across these confessional spaces. In doing so, this article sets British and Irish interests in Jansenism against wider questions of interconfessional dialogue and European reformation, and explores the place of mobility and translation in the framing of the reformation process.