bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial persistence promotes the evolution of antibiotic resistance by increasing survival and mutation rates
Authors: Windels Etthel Martha , Michiels Joran Elie , Fauvart Maarten , Wenseleers Tom , Van den Bergh Bram , Michiels Jan 
Published: January 2019

Abstract
Persisters are transiently antibiotic-tolerant cells that complicate the treatment of bacterial infections. Both theory and experiments have suggested that persisters facilitate genetic resistance by constituting an evolutionary reservoir of viable cells. Here, we provide evidence for a strong positive correlation between persistence and the likelihood to become genetically resistant in natural and lab strains of E. coli. This correlation can be partly attributed to the increased availability of viable cells associated with persistence. However, our data additionally show that persistence is pleiotropically linked with mutation rates. Our theoretical model further demonstrates that increased survival and mutation rates jointly affect the likelihood of evolving clinical resistance. Overall, these results suggest that the battle against antibiotic resistance will benefit from incorporating anti-persister therapies.
Anaerobic degradation of xenobiotic isophthalate by the fermenting bacterium Syntrophorhabdus aromaticivorans
Authors: Junghare Madan , Spiteller Dieter , Schink Bernhard 
Published: January 2019

Abstract
Syntrophorhabdus aromaticivorans is a syntrophically fermenting bacterium that can degrade isophthalate (3-carboxybenzoate). It is a xenobiotic compound which has accumulated in the environment for more than 50 years due to its global industrial usage and can cause negative effects on the environment. Isophthalate degradation by the strictly anaerobic S. aromaticivorans was investigated to advance our understanding of the degradation of xenobiotics introduced into nature, and to identify enzymes that might have ecological significance for bioremediation. Differential proteome analysis of isophthalate- vs benzoate-grown cells revealed over 400 differentially expressed proteins of which only four were unique to isophthalate-grown cells. The isophthalate-induced proteins include a phenylacetate:CoA ligase, a UbiD-like decarboxylase, a UbiX-like flavin prenyltransferase, and a hypothetical protein. These proteins are encoded by genes forming a single gene cluster that putatively codes for anaerobic conversion of isophthalate to benzoyl-CoA. Subsequently, benzoyl-CoA is metabolized by the enzymes of the anaerobic benzoate degradation pathway that were identified in the proteomic analysis. In vitro enzyme assays with cell-free extracts of isophthalate-grown cells indicated that isophthalate is activated to isophthalyl-CoA by an ATP-dependent isophthalate:CoA ligase (IPCL), and subsequently decarboxylated to benzoyl-CoA by a UbiD family isophthalyl-CoA decarboxylase (IPCD) that requires a prenylated flavin mononucleotide (prFMN) cofactor supplied by UbiX to effect decarboxylation. Phylogenetic analysis revealed that IPCD is a novel member of the functionally diverse UbiD family (de)carboxylases. Homologs of the IPCD encoding genes are found in several other bacteria, such as aromatic compound-degrading denitrifiers, marine sulfate-reducers, and methanogenic communities in a terephthalate-degrading reactor. These results suggest that metabolic strategies adapted for degradation of isophthalate and other phthalate are conserved between microorganisms that are involved in the anaerobic degradation of environmentally relevant aromatic compounds.
Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells
Authors: Fiskus Warren , Cai Tianyu , DiNardo Courtney D. , Kornblau Steven M. , Borthakur Gautam , Kadia Tapan M. , Pemmaraju Naveen , Bose Prithviraj , Masarova Lucia , Rajapakshe Kimal , Perera Dimuthu , Coarfa Cristian , Mill Christopher P. , Saenz Dyana T. , Saenz David N. , Sun Baohua , Khoury Joseph D. , Shen Yu , Konopleva Marina , Bhalla Kapil N. 
Published: January 2019

AbstractFirst-generation bromodomain extra-terminal protein (BETP) inhibitors (BETi) (e.g., OTX015) that disrupt binding of BETP BRD4 to chromatin transcriptionally attenuate AML-relevant progrowth and prosurvival oncoproteins. BETi treatment induces apoptosis of AML BPCs, reduces in vivo AML burden and induces clinical remissions in a minority of AML patients. Clinical efficacy of more potent BETis, e.g., ABBV-075 (AbbVie, Inc.), is being evaluated. Venetoclax and A-1210477 bind and inhibit the antiapoptotic activity of BCL2 and MCL1, respectively, lowering the threshold for apoptosis. BETi treatment is shown here to perturb accessible chromatin and activity of enhancers/promoters, attenuating MYC, CDK6, MCL1 and BCL2, while inducing BIM, HEXIM1, CDKN1A expressions and apoptosis of AML cells. Treatment with venetoclax increased MCL1 protein levels, but cotreatment with ABBV-075 reduced MCL1 and Bcl-xL levels. ABBV-075 cotreatment synergistically induced apoptosis with venetoclax or A-1210477 in patient-derived, CD34+ AML cells. Compared to treatment with either agent alone, cotreatment with ABBV-075 and venetoclax was significantly more effective in reducing AML cell-burden and improving survival, without inducing toxicity, in AML-engrafted immune-depleted mice. These findings highlight the basis of superior activity and support interrogation of clinical efficacy and safety of cotreatment with BETi and BCL2 or MCL1 inhibitor in AML.
Episodes of fever in neutropenia in pediatric patients with cancer in Bern, Switzerland, 1993–2012
Authors: Zermatten Maxime G. , Koenig Christa , von Allmen Annina , Agyeman Philipp , Ammann Roland A. 
Published: January 2019

AbstractFever in neutropenia (FN) is the most frequent potentially life threatening complication of chemotherapy for cancer. Prediction of the risk to develop complications, integrated into clinical decision rules, would allow for risk-stratified treatment of FN. This retrospective, single center cohort study in pediatric patients diagnosed with cancer before 17 years, covered two decades, 1993 to 2012. In total, 703 FN episodes in 291 patients with chemotherapy (maximum per patient, 9) were reported here. Twenty-nine characteristics of FN were collected: 6 were patient- and cancer-related, 8 were characteristics of history, 8 of clinical examination, and 7 laboratory results in peripheral blood, all known at FN diagnosis. In total 28 FN outcomes were assessed: 8 described treatment of FN, 6 described microbiologically defined infections (MDI), 4 clinically defined infections, 4 were additional clinical composite outcomes, and 6 outcomes were related to discharge. These data can mainly be used to study FN characteristics and their association with outcomes over time and between centers, and for derivation and external validation of clinical decision rules.
A modified SDS-based DNA extraction method from raw soybean
Authors: Xia Yimiao , Chen Fusheng , Du Yan , Liu Chen , Bu Guanhao , Xin Ying , Liu Boye 
Published: January 2019

Abstract
Soybean is the most important genetically modified (GM) oilseed worldwide. Regulations relating to the approval of biotech soybean varieties and product labeling demand accurate and reliable detection techniques to screen for GM soya. High-quality extracted DNA is essential for DNA-based monitoring methods. Thus, four widely used protocols (SDS, CTAB, DP305, and DNeasy Plant Mini Kit) were compared in the present study to explore the most efficient DNA extraction method for raw soya matrix. The SDS-based method showed the highest applicability. Then crucial factors influencing DNA yield and purity, such as SDS lysis buffer component concentrations and organic compounds used to isolate DNA, were further investigated to improve the DNA obtained from raw soybean seeds, which accounts for the innovation of this work. As a result, lysis buffer (2% SDS (w/v), 150 mM NaCl, 50 mM Tris/HCl, 50 mM EDTA, pH 8.0) and organic reagents including chloroform/isoamyl alcohol (24:1, v/v) (C: I), isopropanol, and ethanol corresponding to the extraction and first and second precipitation procedures, respectively, were used in the optimized SDS method. The optimized method was verified by extracting approximately 2020–2444 ng DNA/mg soybean with A260/280 ratios of 1.862–1.954 from five biotech and non-biotech soybean varieties. Only 0.5 mg of soya was required to obtain enough DNA for PCR amplification using the optimized SDS-based method. These results indicate that the screening protocol in the present study achieves the highest suitability and efficiency for DNA isolation from raw soya seed flour.
Effects on oscillation mechanism and design of grid‐voltage feedforward in grid‐tied converter under weak grid
Authors: Wang Guoning , Du Xiong , Shi Ying , Yang Yougeng , Sun Pengju , Li Guanghui 
Published: January 2019

Grid‐voltage feedforward control is widely used in grid‐tied converters. The reported studies show that the grid‐voltage feedforward may reduce the system stability margin, and may lead to oscillation problem in renewable power generation system. This study revisits the effect of voltage feedforward control on system stability and especially focuses on low frequency oscillation with impedance‐based method. The low frequency oscillation usually happens in industry around 100 Hz and shows frequency coupling characteristics. A converter equivalent impedance which includes the effects of voltage feedforward and also covers the frequency coupling introduced by phase locked loop (PLL) is established. Based on the built impedance, the effect on oscillation mechanism with voltage feedforward and PLL is revealed. The results show that the voltage feedforward could increase the system stability margin and may be employed to improve the system stability. Then how to design an optimal proportional voltage feedforward control is demonstrated. Experimental results verify the theoretical analysis and the design of the proportional grid‐voltage feedforward control.
Robust multi‐objective blood glucose control in Type‐1 diabetic patient
Authors: Mandal Sharmistha , Sutradhar Ashoke 
Published: January 2019

In this study, an automatic robust multi‐objective controller has been proposed for blood glucose (BG) regulation in Type‐1 Diabetic Mellitus (T1DM) patient through subcutaneous route. The main objective of this work is to control the BG level in T1DM patient in the presence of unannounced meal disturbances and other external noises with a minimum amount of insulin infusion rate. The multi‐objective output‐feedback controller with H∞, H2 and pole‐placement constraints has been designed using linear matrix inequality technique. The designed controller for subcutaneous insulin delivery was tested on in silico adult and adolescent subjects of UVa/Padova T1DM metabolic simulator. The experimental results show that the closed‐loop system tracks the reference BG level very well and does not show any hypoglycaemia effect even during the long gap of a meal at night both for in silico adults and adolescent. In the presence of 50 gm meal disturbance, average adult experience normoglycaemia 92% of the total simulation time and hypoglycaemia 0% of total simulation time. The robustness of the controller has been tested in the presence of irregular meals and insulin pump noise and error. The controller yielded robust performance with a lesser amount of insulin infusion rate than the other designed controllers reported earlier.
Study on clearance optimisation and altitude correction of 750 kV AC side for UHVDC converter transformer
Authors: Ding Yujian , Yao Xiuyuan , Gu Chen , Wang Xi 
Published: January 2019

AC system which ±800 kV converter station access to commonly used 500 kV voltage level. With the construction of the Northwest Energy Base, a large number of ultra‐high‐voltage direct current (UHVDC) project are constructing. The backbone voltage in the northwest region is 750 kV. Phase or phase‐to‐ground clearance the converter transformer 750 kV AC side required will affect the length of the valve hall and the highest altitude of the project close to 3000 m. In order to optimise the 750 kV AC side and meet the engineering requirements in high altitude areas, this paper carried out the true phase‐to‐ground and phase–phase discharge characteristics test in the gap of 750 kV AC side in Beijing and Tibet, and the gap discharge voltage was then corrected for altitude. At last, the distance at different altitudes of 3000 m and below between the phase‐ground and the phase‐to‐phase at the AC side of converter transformer is obtained. The results provide the design of UHV converter station in Northwest China with technical support.
Influence factors and reasonable arrangement of corridor width of ±800 kV HVDC and 750 kV HVAC hybrid transmission lines
Authors: Zhang Qian , Li Yinfei , Li Xuebao , Lu Tiebing 
Published: January 2019

With the development of economy and the increased demand of power energy, it is unavoidable that high‐voltage direct current (HVDC) and high‐voltage alternating current (HVAC) transmission lines are in the same corridor. In order to minimise the land resource and meet the requirements of the electromagnetic environment, it is necessary to accurately predict the hybrid electric field under the hybrid transmission lines. The ±800 kV HVDC and 750 kV HVAC parallel transmission lines of parallel erection are chosen to be analysed. The corridor width with a different separation distance is calculated, and the minimum corridor width under this voltage‐level combination is obtained according to the control value of the hybrid electric field recommended at home and abroad in a non‐residential area. Increasing the height of DC or AC lines can reduce the corridor width. At a fixed separation distance, the minimum height of the AC line can be obtained when the height of the DC line is set at a certain value. Meanwhile the change of the corridor width is analysed with different heights of DC lines and AC lines. Based on the above analysis, the reasonable arrangement is made.
A 3D kinematic Babcock Leighton solar dynamo model sustained by dynamic magnetic buoyancy and flux transport processes
Authors: Kumar Rohit , Jouve Laurène , Nandy Dibyendu 
Published: January 2019

Context. Magnetohydrodynamic interactions between plasma flows and magnetic fields is fundamental to the origin and sustenance of the 11-year sunspot cycle. These processes are intrinsically three-dimensional (3D) in nature.
Aims. Our goal is to construct a 3D solar dynamo model that on the one hand captures the buoyant emergence of tilted bipolar sunspot pairs, and on the other hand produces cyclic large-scale field reversals mediated via surface flux-transport processes – that is, the Babcock-Leighton mechanism. Furthermore, we seek to explore the relative roles of flux transport by buoyancy, advection by meridional circulation, and turbulent diffusion in this 3D dynamo model.
Methods. We perform kinematic dynamo simulations where the prescribed velocity field is a combination of solar-like differential rotation and meridional circulation, along with a parametrized turbulent diffusivity. We use a novel methodology for modeling magnetic buoyancy through field-strength-dependent 3D helical up-flows that results in the formation of tilted bipolar sunspots.
Results. The bipolar spots produced in our simulations participate in the process of poloidal-field generation through the Babcock-Leighton mechanism, resulting in self-sustained and periodic large-scale magnetic field reversal. Our parameter space study varying the amplitude of the meridional flow, the convection zone diffusivity, and parameters governing the efficiency of the magnetic buoyancy mechanism reveal their relative roles in determining properties of the sunspot cycle such as amplitude, period, and dynamical memory relevant to solar cycle prediction. We also derive a new dynamo number for the Babcock-Leighton solar dynamo mechanism which reasonably captures our model dynamics.
Conclusions. This study elucidates the relative roles of different flux-transport processes in the Sun’s convection zone in determining the properties and physics of the sunspot cycle and could potentially lead to realistic, data-driven 3D dynamo models for solar-activity predictions and exploration of stellar magnetism and starspot formation in other stars.
Limits of long-term selection against Neandertal introgression
Authors: Petr Martin , Pääbo Svante , Kelso Janet , Vernot Benjamin 
Published: January 2019

Significance
Since the discovery that all non-Africans inherit 2% of their genomes from Neandertal ancestors, there has been a great interest in understanding the fate and effects of introgressed Neandertal DNA in modern humans. A number of recent studies have claimed that there has been continuous selection against introgressed Neandertal DNA over the last 55,000 years. Here, we show that there has been no long-term genome-wide removal of Neandertal DNA, and that the previous result was due to incorrect assumptions about gene flow between African and non-African populations. Nevertheless, selection did occur following introgression, and its effect was strongest in regulatory regions, suggesting that Neandertals may have differed from humans more in their regulatory than in their protein-coding sequences.
Varroa destructorfeeds primarily on honey bee fat body tissue and not hemolymph
Authors: Ramsey Samuel D. , Ochoa Ronald , Bauchan Gary , Gulbronson Connor , Mowery Joseph D. , Cohen Allen , Lim David , Joklik Judith , Cicero Joseph M. , Ellis James D. , Hawthorne David , vanEngelsdorp Dennis 
Published: January 2019

SignificanceVarroa destructorcauses considerable damage to honey bees and subsequently the field of apiculture through just one process: feeding. For five decades, we have believed that these mites consume hemolymph like a tick consumes blood, and thatVarroacause harm primarily by vectoring viruses. Our work shows that they cause damage more directly.Varroaexternally digest and consume fat body tissue rather than blood. These findings explain the failure of some previous attempts at developing effectively targeted treatment strategies forVarroacontrol. Furthermore, it provides some explanation for the diverse array of debilitating pathologies associated withVarroathat were unexplained by hemolymph removal alone. Our work provides a path forward for the development of novel treatment strategies forVarroa.
Molecular and Cellular Effect of Angiotensin 1–7 on Hypertensive Kidney Disease
Authors: Chen Yuanjian , Zhao Wenyuan , Liu Chang , Meng Weixin , Zhao Tieqiang , Bhattacharya Syamal K , Sun Yao 
Published: January 2019

Abstract

BACKGROUND
Studies implicate that angiotensin 1–7 (Ang1-7) imparts protective effects in the kidney. However, its relevance in hypertensive kidney disease is not fully understood. The purpose of this study was to explore the role of Ang1-7 on renal damage/remodeling during hypertension and its potential underlying molecular–cellular mechanisms.

METHODS
Hypertension was induced in adult Sprague–Dawley rats by infusion of aldosterone (ALDO; 0.75 μg/hour) for 4 weeks with or without co-treatment of Ang1-7 (1 mg/kg/day). Untreated rats served as controls. Systolic blood pressure was monitored by tail-cuff technique. Renal fibrosis was evaluated by picrosirius red staining and renal collagen volume fraction was quantitated using imaging analyzing system. The expression of profibrotic factors [transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-D (PDGF-D), fibroblast growth factor-1 (FGF-1), vascular endothelial growth factor-D (VEGF-D), and tissue inhibitors of metalloproteinases (TIMPs)] and free radical producing enzymes (inducible nitric oxide synthase and nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) in the kidney were examined by reverse transcription–polymerase chain reaction and western blot. Renal oxidative stress was assessed by malondialdehyde (MDA) measurement.

RESULTS
Chronic ALDO infusion caused hypertension and hypertensive renal disease represented as glomerular damage/sclerosis. Ang1-7 co-treatment did not affect blood pressure in ALDO-treated rats, but significantly attenuated the glomerular damage/fibrosis. ALDO treatment significantly elevated renal expression of profibrogenic factors, including TGF-β1, TIMP-1/TIMP-2, FGF-1, PDGF-D, and VEGF-D, whereas Ang1-7 co-treatment significantly reduced renal TGF-β1, TIMP-1/TIMP-2, and FGF-1, but not PDGF-D and VEGF-D. Furthermore, ALDO infusion elevated NADPH oxidase (gp91phox) and MDA in the kidney, which was attenuated by Ang1-7 co-treatment.

CONCLUSIONS
Ang1-7 plays a protective role in the hypertensive kidney disease independent of blood pressure. The beneficial effects of Ang1-7 are likely mediated via suppressing TGF-β/FGF-1 pathways and oxidative stress.
SRG extractor: a skinny reference genome approach for reduced-representation sequencing
Authors: Torkamaneh Davoud , Laroche Jérôme , Rajcan Istvan , Belzile François 
Published: January 2019

Abstract

Motivation
Reduced-representation sequencing is a genome-wide scanning method for simultaneous discovery and genotyping of thousands to millions of single nucleotide polymorphisms that is used across a wide range of species. However, in this method a reproducible but very small fraction of the genome is captured for sequencing, while the resulting reads are typically aligned against the entire reference genome.

Results
Here we present a skinny reference genome approach in which a simplified reference genome is used to decrease computing time for data processing and to increase single nucleotide polymorphism counts and accuracy. A skinny reference genome can be integrated into any reduced-representation sequencing analytical pipeline.

Availability and implementation
https://bitbucket.org/jerlar73/SRG-Extractor.

Supplementary information
Supplementary data are available at Bioinformatics online.
Generalized rich-club ordering in networks
Authors: Cinelli Matteo 
Published: January 2019

Abstract
Rich-club ordering refers to the tendency of nodes with a high degree to be more interconnected than expected. In this article, we consider the concept of rich-club ordering when generalized to structural measures that differ from the node degree and to non-structural measures (i.e. to node metadata). The differences in considering rich-club ordering with respect to both structural and non-structural measures is then discussed in terms of employed coefficients and of appropriate null models (link rewiring vs. metadata reshuffling). Once a framework for the evaluation of generalized rich-club ordering is defined, we investigate such a phenomenon in real networks provided with node metadata. By considering different notions of node richness, we compare structural and non-structural rich-club ordering, observing how external information about the network nodes is able to validate the presence of rich-clubs in networked systems.