bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Aurora kinase inhibitor Hesperadin reveals epistatic interaction between Plasmodium falciparum PfArk1 and PfNek1 kinases
Authors: Morahan Belinda J. , Abrie Clarissa , Al-Hasani Keith , Batty Mitchell B. , Corey Victoria , Cowell Anne N. , Niemand Jandeli , Winzeler Elizabeth A. , Birkholtz Lyn-Marie , Doerig Christian , Garcia-Bustos Jose F. 
Published: November 2020

AbstractMitosis has been validated by numerous anti-cancer drugs as being a druggable process, and selective inhibition of parasite proliferation provides an obvious opportunity for therapeutic intervention against malaria. Mitosis is controlled through the interplay between several protein kinases and phosphatases. We show here that inhibitors of human mitotic kinases belonging to the Aurora family inhibit P. falciparum proliferation in vitro with various potencies, and that a genetic selection for mutant parasites resistant to one of the drugs, Hesperadin, identifies a resistance mechanism mediated by a member of a different kinase family, PfNek1 (PF3D7_1228300). Intriguingly, loss of PfNek1 catalytic activity provides protection against drug action. This points to an undescribed functional interaction between Ark and Nek kinases and shows that existing inhibitors can be used to validate additional essential and druggable kinase functions in the parasite.
Fairy circles in Namibia are assembled from genetically distinct grasses
Authors: Kappel Christian , Illing Nicola , Huu Cuong Nguyen , Barger Nichole N. , Cramer Michael D. , Lenhard Michael , Midgley Jeremy J. 
Published: November 2020

AbstractFairy circles are striking regularly sized and spaced, bare circles surrounded by Stipagrostis grasses that occur over thousands of square kilometres in Namibia. The mechanisms explaining their origin, shape, persistence and regularity remain controversial. One hypothesis for the formation of vegetation rings is based on the centrifugal expansion of a single individual grass plant, via clonal growth and die-back in the centre. Clonality could explain FC origin, shape and long-term persistence as well as their regularity, if one clone competes with adjacent clones. Here, we show that for virtually all tested fairy circles the periphery is not exclusively made up of genetically identical grasses, but these peripheral grasses belong to more than one unrelated genet. These results do not support a clonal explanation for fairy circles. Lack of clonality implies that a biological reason for their origin, shape and regularity must emerge from competition between near neighbor individuals within each fairy circle. Such lack of clonality also suggests a mismatch between longevity of fairy circles versus their constituent plants. Furthermore, our findings of lack of clonality have implications for some models of spatial patterning of fairy circles that are based on self-organization.
Bacterial second messenger 3′,5′-cyclic diguanylate attracts Caenorhabditis elegans and suppresses its immunity
Authors: Angeloni Joseph , Dong Yuqing , Wang Zeneng , Cao Min 
Published: November 2020

AbstractCyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes. In this study, we found that Caenorhabditis elegans can detect and are attracted to multiple signal molecules produced by Vibrio cholerae, specifically the 3′,5′-cyclic diguanylate (c-di-GMP), even though this bacterium kills the host at a high rate. C-di-GMP is sensed through C. elegans olfactory AWC neurons, which then evokes a series of signal transduction pathways that lead to reduced activity of two key stress response transcription factors, SKN-1 and HSF-1, and weakened innate immunity. Taken together, our study elucidates the role of c-di-GMP in interkingdom communication. For C. elegans, bacterial c-di-GMP may serve as a cue that they can use to detect food. On the other hand, preexposure to low concentrations of c-di-GMP may impair their immune response, which could facilitate bacterial invasion and survival.
Directional element for faulty feeder identification of high‐resistance fault in high‐surety power supply systems
Authors: Rouhani Roja , Sadeghkhani Iman , Guerrero Josep M. 
Published: November 2020

AbstractThe high‐surety power supply systems are gaining great attention to enhance the reliability of uninterruptable power supplies. A high‐resistance fault along a high‐surety power supply feeder results in a low fault current, making the conventional high‐surety power supply protection strategy ineffective. To address this problem, this paper develops a directional fault protection strategy for high‐resistance fault detection and faulty feeder identification. Using the intelligent electronic device, the feeder current is sampled and normalised. Then, the fault‐imposed component of the current signal is calculated. This component is added to the input of the forced Helmholtz oscillator to increase the sensitivity of the proposed protection scheme for the detection of high‐resistance faults. The output of the forced Helmholtz oscillator equation is adopted as the fault detection criterion because it is infinity for reverse faults while it is lower than 1 for forward faults, facilitating the fault detection. The developed strategy is local and can detect and classify both pole‐to‐ground and pole‐to‐pole high‐resistance faults. Also, it is effective for both unidirectional and bidirectional converters. The merits of the proposed protection strategy are demonstrated through several fault scenarios using a ±375 V high‐surety power supply system.
Dynamic performance improvement of isolated power system using intelligently controlled SMES
Authors: Zargar Mubashar Yaqoob , Mufti Mairaj ud Din , Lone Shameem Ahmad 
Published: November 2020

AbstractIsolated power system comprising of wind, diesel and energy storage presents an effective economical approach for supplying power. Advanced and intelligent control techniques are required to improve the power dispatch between storage devices and wind‐diesel system especially during disturbances. This paper focuses on development of one step ahead adaptively controlled superconducting magnetic energy storage (SMES) for smoothing the power fluctuations of a standalone wind‐diesel power system. Two sets of gate turn off (GTO) converters are utilized for obtaining a four quadrant operation of SMES system. System is represented by a third order autoregressive discrete time model. For estimating the system parameters online, recursive least square algorithm is used. System is considered as a two input two output system, where real and reactive powers demanded by SMES are the control signals issued by the controller. To restrict the energy trade within limits, constraints are imposed on the SMES current. Discrete time model of SMES is used for converting SMES current constraints into the energy level predictions and a separate model is then used for imposing the constraints. Scheme is tested for two disturbances and in both the cases, SMES current constraints are never violated while reducing the frequency and voltage deviations significantly.
Optimal power flow of MT‐HVDC system connected large offshore wind farms using mixed‐integer semi‐definite programming approach
Authors: Pathak Nikhil , Hu Zechun 
Published: November 2020

AbstractTypically offshore wind farms are connected to the onshore AC grid networks using voltage source converter based MT‐HVDC networks. This article aims to formulating optimal power flow (OPF) problem of MT‐HVDC system connected large offshore wind farms using mixed‐integer semi‐definite programming approach. Both constant power and droop control modes of voltage source converter converters are considered in OPF formulation. Main objective of OPF is to minimize DC power losses and simultaneously optimizing droop gains of the converters. OPF problem is solved using SDP relaxation; while its exactness is discussed using graphical properties. It is found that MT‐HVDC system exhibit acyclic graph property which guarantees that SDP relaxation would give either rank‐1 or ‐2 solutions. For rank‐2 solutions, an iterative rank reduction algorithm is introduced to achieve rank‐1 solutions from which global optimal solutions could be recovered easily. The comparative analysis is also performed with previously employed optimization methods used to solve the OPF problem. Furthermore, steady state solutions obtained from the proposed OPF formulation are also cross‐verified using dynamic simulation studies of offshore wind farms connected MT‐HVDC networks.
Constraints on the astrophysical environment of binaries with gravitational-wave observations
Authors: Cardoso Vitor , Maselli Andrea 
Published: November 2020

Aims. The dynamics of coalescing compact binaries can be affected by the environment in which the systems evolve, leaving detectable signatures in the emitted gravitational signal. In this paper, we investigate the ability of gravitational-wave detectors to constrain the nature of the environment in which compact binaries merge.
Methods. We parametrized a variety of environmental effects by modifying the phase of the gravitational signal emitted by black hole and neutron star binaries. We infer the bounds on such effects by current and future generations of interferometers, studying their dependence on the binary’s parameters.
Results. We show that the strong dephasing induced by accretion and dynamical friction can constrain the density of the surrounding medium to orders of magnitude below those of accretion disks. Planned detectors, such as LISA or DECIGO, will be able to probe densities typical of those of dark matter.
Strong Hαemission in the young planetary mass companion 2MASS J0249−0557 c
Authors: Chinchilla P. , Béjar V. J. S. , Lodieu N. , Zapatero Osorio M. R. , Gauza B. 
Published: November 2020

Aims.Our objective is the optical and near-infrared spectroscopic characterisation of 2MASS J0249−0557 c, a recently discovered young planetary mass companion to theβPictoris (~25 Myr) member 2MASS J0249−0557.Methods.Using the Visible and Infrared Survey Telescope for Astronomy Hemisphere Survey and the Two Micron All Sky Survey (2MASS) data, we independently identified the companion 2MASS J0249−0557 c. We also obtained low-resolution optical spectroscopy of this object using the Optical System for Imaging and low-intermediate-Resolution Integrated Spectroscopy spectrograph at the Gran Telescopio Canarias, and near-infrared spectroscopy using the Son of Isaac spectrograph on the New Technology Telescope.Results.We classified 2MASS J0249−0557 c with a spectral type of L2.5 ± 0.5 in the optical and L3 ± 1 in the near-infrared. We identified several spectroscopic indicators of youth both in the optical and in the near-infrared that are compatible with the age of theβPictoris moving group: strong absorption due to oxides, weak alkaline atomic lines, and a triangular shape of theH-band pseudo-continuum. We also detect a strong Hαemission, with a pseudo-equivalent width (pEW) of −90−40+20Å, which seems persistent at timescales from several days to a few years. This indicates strong chromospheric activity or disk accretion. Although many M-type brown dwarfs have strong Hαemission, this target is one of the very few L-type planetary mass objects in which this strong Hαemission has been detected. Lithium absorption at 6708 Å is observed with pEW ≲5 Å. We also computed the binding energy of 2MASS J0249−0557 c and obtained an (absolute) upper limit ofU= (−8.8 ± 4.4) × 1032J.Conclusions.Similarly to other young brown dwarfs and isolated planetary mass objects, strong Hαemission due to accretion or chromospheric activity is also present in young planetary mass companions at ages of some dozen million years. We also found that 2MASS J0249−0557 c is one of the wide substellar companions with the lowest binding energy known to date.
Digital Literacy Movement by Former Migrant Workers in Wonosobo, Central Java
Authors: Novianti Wiwik , Istiyanto S. Bekti 
Published: November 2020

The digital literacy movement is mostly centered in big cities even though internet users in rural areas are also very high. In Tracap Village, Wonosobo District, there is a community of former migrant workers who care about digital literacy. Living in a remote area does not mean that the people there are backward but it makes them more creative. This paper would like to describe the digital literacy movement carried out by former migrant workers in Wonosobo Regency, the goals to be achieved and their strategies in conducting digital literacy.
The research method used in this study is qualitative. Data collection is done by in-depth interviews, observation, and document analysis.
The study found that the experience of being a migrant worker who had difficulty communicating with families in the village was the main driver for former migrant workers in Wonosobo to share their knowledge about internet use with villagers. The goal is that communication between family members continues to exist even though one of his family is abroad.
The strategies carried out to provide knowledge and skills in using the internet started from subscribing to the internet which can be accessed free of charge by citizens to open internet classes for migrant workers’ children. The internet which was originally only used as a medium of communication with families abroad developed into something productive, namely to help with school or work assignments, sell online and make games.
Comparison of Prostate MRI Lesion Segmentation Agreement Between Multiple Radiologists and a Fully Automatic Deep Learning System
Authors: Schelb Patrick , Tavakoli Anoshirwan Andrej , Tubtawee Teeravut , Hielscher Thomas , Radtke Jan-Philipp , Görtz Magdalena , Schütz Viktoria , Kuder Tristan Anselm , Schimmöller Lars , Stenzinger Albrecht , Hohenfellner Markus , Schlemmer Heinz-Peter , Bonekamp David 
Published: November 2020

Purpose A recently developed deep learning model (U-Net) approximated the clinical performance of radiologists in the prediction of clinically significant prostate cancer (sPC) from prostate MRI. Here, we compare the agreement between lesion segmentations by U-Net with manual lesion segmentations performed by different radiologists.
Materials and Methods 165 patients with suspicion for sPC underwent targeted and systematic fusion biopsy following 3 Tesla multiparametric MRI (mpMRI). Five sets of segmentations were generated retrospectively: segmentations of clinical lesions, independent segmentations by three radiologists, and fully automated bi-parametric U-Net segmentations. Per-lesion agreement was calculated for each rater by averaging Dice coefficients with all overlapping lesions from other raters. Agreement was compared using descriptive statistics and linear mixed models.
Results The mean Dice coefficient for manual segmentations showed only moderate agreement at 0.48–0.52, reflecting the difficult visual task of determining the outline of otherwise jointly detected lesions. U-net segmentations were significantly smaller than manual segmentations (p < 0.0001) and exhibited a lower mean Dice coefficient of 0.22, which was significantly lower compared to manual segmentations (all p < 0.0001). These differences remained after correction for lesion size and were unaffected between sPC and non-sPC lesions and between peripheral and transition zone lesions.
Conclusion Knowledge of the order of agreement of manual segmentations of different radiologists is important to set the expectation value for artificial intelligence (AI) systems in the task of prostate MRI lesion segmentation. Perfect agreement (Dice coefficient of one) should not be expected for AI. Lower Dice coefficients of U-Net compared to manual segmentations are only partially explained by smaller segmentation sizes and may result from a focus on the lesion core and a small relative lesion center shift. Although it is primarily important that AI detects sPC correctly, the Dice coefficient for overlapping lesions from multiple raters can be used as a secondary measure for segmentation quality in future studies.
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Novel Long-Acting Buprenorphine Medications for Opioid Dependence: Current Update
Authors: Soyka Michael 
Published: November 2020

AbstractOpioid maintenance treatment with oral methadone or sublingual buprenorphine is the first-line treatment in opioid dependence. Three novel long-acting buprenorphine formulations have been approved or will be available soon: for subcutaneous weekly and monthly application, the depot formulations CAM 2038 (Buvidal®), the monthly depot formulation RBP-6000 (Sublocade™), and a 6-month buprenorphine implant (Probuphine™). Clinical data available so far on the efficacy of these 3 medications are given, and possible clinical implications are discussed.
Facile Pyridine S
N
Ar Reactions via N-Phosphonium–Pyridinium Intermediates
Authors: McNally Andrew , Boyle Benjamin T. , Koniarczyk J. Luke 
Published: November 2020

AbstractHere we report that N-phosphonium pyridinium intermediates are unusually reactive for pyridine SNAr reactions. Specifically, forming phosphonium salts from halopyridines typically requires elevated temperatures and Lewis acid additives. The alternative activation mode described in this paper permits C–P bond formation to occur at ambient temperatures in many cases, and functions across a broad range of substrates.
An Efficient Substrate-Induced Method for the Synthesis of CF3-Substituted Cyclopropanes by Metal-Free Reaction of Trifluoromethyl Styrylisoxazoles with Nitromethane
Authors: Li Feng , Ma Hai , Zhao Qing-he , Yu Guang-hao , Meng Ye-chen , Sui Feng , Yang Mi-yi , Liu Li , Li Hui-jie 
Published: November 2020

AbstractA series of (trifluoromethyl)cyclopropanes (TFCPs) tolerating a broad range of functional groups, known as tert-butyl bioisosteres, have been obtained from the cyclization reaction between nitromethane­ and 5-[β-(trifluoromethyl)styryl]isoxazoles in 70–94% yields and 75:25 to 90:10 dr. This method offers practical access to this cyclopropyl moiety of pharmacological interest, employing an inorganic base under phase-transfer conditions.
Value of Neutrophil to Lymphocyte Ratio in Early Prediction of Meconium Aspiration Syndrome
Authors: Gad Suzan , Alkhalafawi Abeer , Raza Syed , Hesham Mervat , Sheta Mohamed 
Published: November 2020

AbstractMeconium aspiration syndrome (MAS) is a serious neonatal condition. Prediction of MAS is challenging particularly in low-resource setting. Neutrophil to lymphocyte ratio (NLR) is a new simple index used for diagnosis of many inflammatory conditions. The present study was an attempt to determine whether NLR can predict the occurrence of MAS. The present study included 101 children with meconium-stained amniotic fluid. They comprised 22 patients who developed MAS and 79 neonates who didn't have the condition. All neonates were subjected to careful analysis of maternal and perinatal history in addition to thorough clinical assessment and radiological and laboratory evaluation. Blood samples from the umbilical cord were collected at birth and were used to obtain complete blood counts and C-reactive protein (CRP) assay. Univariate analysis revealed that elevated CRP levels, increased NLR, and 5-minute Apgar score of <7 were significant risk factors for the occurrence of MAS. Multivariate analysis revealed that low 5-minute Apgar score and increased NLR remained as significant risk factors of MAS. Receiver operating characteristic curve analysis showed good performance of NLR in prediction of MAS. NLR is useful in prediction of MAS in term neonates with meconium-stained amniotic fluid.
A Structured, Microsurgical Training Curriculum Improves the Outcome in Lower Extremity Reconstruction Free Flap Residency Training: The Ludwigshafen Concept
Authors: Boecker Arne , Kornmann Jonas , Xiong Lingyun , Harhaus Leila , Aman Martin , Koepple Christoph , Fischer Sebastian , Will Patrick A. , Kneser Ulrich , Hirche Christoph 
Published: November 2020

Abstract
Background Risk stratification, economic pressure, and a flat learning curve make the realization and development of proper microsurgical skills and competences a challenging task in the daily clinical practice. In previous studies, we were able to show that microsurgical procedures, e.g., free flaps and replantations, are safe training procedures and teachable in daily clinical practice in view of certain issues of risk stratification. The present study aims to evaluate further improvements in terms of safety and complication rates for free flaps as a training procedure after introduction and continuous implementation of a structured in-house training curriculum for microsurgical skills and competences and a 24-hour free accessible microsurgical training facility for the plastic surgery resident.
Methods This retrospective comparative cohort study was conducted to review whether microsurgical skills for free flaps to the lower extremity can further be improved after implementation of the curriculum and a 24-hour accessible training facility. Therefore, we compared cohort A before (2009–2012) and B after (2014–2017) implementation. Patient demographics, procedural characteristics, and outcome parameters for free tissue transfer of the lower extremity were evaluated.
Results The comparison of both cohorts showed a significantly reduced postoperative complication rate for cohort B (p <0.05). Furthermore, operation time was shorter, and the hospital stay could be significantly decreased (p <0.01). Workhorse flaps for plastic surgical training were the anterior lateral thigh (ALT) flap or the musculus latissimus dorsi (LD) flap. However, even more complex procedures with arteriovenous loops could be safely performed by plastic surgery residents under the supervision of the senior surgeon in exceptional cases.
Conclusion The implementation of a regularly held, microsurgical in-house training curriculum with 24-hour accessible training facility improves procedural and outcome parameters for free flaps to the lower extremity for surgical residents and is an elementary part of skills and competency training. However, risk stratification, repeated surgical exposure, expertise, and institutional infrastructures are essential and must be taken into consideration.