bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures
Authors: van der Waals Lizet M. , Laoukili Jamila , Jongen Jennifer M. J. , Raats Danielle A. , Borel Rinkes Inne H. M. , Kranenburg Onno 
Published: January 2019

AbstractReactive oxygen species (ROS) function as second messengers in signal transduction, but high ROS levels can also cause cell death. MTH1 dephosphorylates oxidized nucleotides, thereby preventing their incorporation into DNA and protecting tumour cells from oxidative DNA damage. Inhibitors of MTH1 (TH588 and (S)-crizotinib) were shown to reduce cancer cell viability. However, the MTH1-dependency of the anti-cancer effects of these drugs has recently been questioned. Here, we have assessed anti-tumour effects of TH588 and (S)-crizotinib in patient-derived 3D colorectal cancer cultures. Hypoxia and reoxygenation – conditions that increase intracellular ROS levels – increased sensitivity to (S)-crizotinib, but not to TH588. (S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds. Furthermore, we show that both compounds induced DNA damage that could not be prevented by adding the ROS inhibitor N-acetyl-L-cysteine. Moreover, adding ROS-modulating compounds did not alter the reduction in viability in response to TH588 and (S)-crizotinib. We conclude that TH588 and (S)-crizotinib have very clear and distinct anti-tumour effects in 3D colorectal cancer cultures, but that these effects most likely occur through distinct and ROS-independent mechanisms.
A fast and adaptable method for high accuracy integration of the time-dependent Schrödinger equation
Authors: Wells Daniel , Quiney Harry 
Published: January 2019

AbstractWe present an adaptable, fast, and robust method for integrating the time-dependent Schrödinger equation. We apply the method to calculations of High Harmonic (HHG) and Above Threshold Ionisation (ATI) spectra for a single atomic electron in an intense laser field. Our approach implements the stabilized bi-conjugate gradient method (BiCG-STAB) for solving a sparse linear system to evolve the electronic wavefunction in time. The use of this established method makes the propagation scheme less restrictive compared to other schemes which may have particular requirements for the form of the equation, such as use of a three-point finite-difference approximation for spatial derivatives. Our method produces converged solutions significantly faster than existing methods, particularly if high accuracy is required. We demonstrate that this approach is suitable for a range of different parameters and show that in many circumstances significant gains can be made with the use of a fourth-order time propagator as opposed to the more common second-order Crank-Nicolson (CN) method.
A Disease Resistance Elicitor Laminarin Enhances Tea Defense against a Piercing Herbivore Empoasca (Matsumurasca) onukii Matsuda
Authors: Xin Zhaojun , Cai Xiaoming , Chen Shenglong , Luo Zongxiu , Bian Lei , Li Zhaoqun , Ge Lingang , Chen Zongmao 
Published: January 2019

AbstractThe tea plant (Camellia sinensis) suffers heavily from a harmful piercing pest, the tea green leafhopper (TLH)Empoasca(Matsumurasca)onukiiMatsuda. In the present study, we studied the effect of an efficient elicitor of plant disease resistance, the β-1,3-glucan laminarin, on the induced defense against TLH in tea plants. Defense responses elicited by laminarin in tea include the activation of mitogen-activated protein kinases and WRKY, the burst of H2O2, salicylic acid, and abscisic acid, and the accumulation of direct-defense chemicals (including chitinase, phenylalanine ammonia lyase, callose, polyphenol oxidase, and flavonol synthase), as well as the production of volatile compounds. The laminarin-treated tea plants reduced the performance of TLH and enhanced the attractiveness to the egg parasitoid wasp of TLH,Stethynium empoascaeSubba Rao. In the field experiment, laminarin application effectively reduced the number of TLH by attracting parasitoids. These results suggest that laminarin can induce protection against TLH by regulating signaling pathways in tea plant. Our study also proposes an environment friendly strategy for the integrated management of an economically important piercing pest.
Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome
Authors: Thompson Rachel , Bonne Gisèle , Missier Paolo , Lochmüller Hanns 
Published: January 2019

Abstract
Despite recent scientific advances, most rare genetic diseases — including most neuromuscular diseases — do not currently have curative gene-based therapies available. However, in some cases, such as vitamin, cofactor or enzyme deficiencies, channelopathies and disorders of the neuromuscular junction, a confirmed genetic diagnosis provides guidance on treatment, with drugs available that may significantly alter the disease course, improve functional ability and extend life expectancy. Nevertheless, many treatable patients remain undiagnosed or do not receive treatment even after genetic diagnosis. The growth of computer-aided genetic analysis systems that enable clinicians to diagnose their undiagnosed patients has not yet been matched by genetics-based decision-support systems for treatment guidance. Generating a ‘treatabolome’ of treatable variants and the evidence for the treatment has the potential to increase treatment rates for treatable conditions. Here, we use the congenital myasthenic syndromes (CMS), a group of clinically and genetically heterogeneous but frequently treatable neuromuscular conditions, to illustrate the steps in the creation of a treatabolome for rare inherited diseases. We perform a systematic review of the evidence for pharmacological treatment of each CMS type, gathering evidence from 207 studies of over 1000 patients and stratifying by genetic defect, as treatment varies depending on the underlying cause. We assess the strength and quality of the evidence and create a dataset that provides the foundation for a computer-aided system to enable clinicians to gain easier access to information about treatable variants and the evidence they need to consider.
Hidden or missing outflows in highly obscured galaxy nuclei?
Authors: Falstad N. , Hallqvist F. , Aalto S. , König S. , Muller S. , Aladro R. , Combes F. , Evans A. S. , Fuller G. A. , Gallagher J. S. , García-Burillo S. , González-Alfonso E. , Greve T. R. , Henkel C. , Imanishi M. , Izumi T. , Mangum J. G. , Martín S. , Privon G. C. , Sakamoto K. , Veilleux S. , van der Werf P. P. 
Published: January 2019

Context. Understanding the nuclear growth and feedback processes in galaxies requires investigating their often obscured central regions. One way to do this is to use (sub)millimeter line emission from vibrationally excited HCN (HCN-vib), which is thought to trace warm and highly enshrouded galaxy nuclei. It has been suggested that the most intense HCN-vib emission from a galaxy is connected to a phase of nuclear growth that occurs before the nuclear feedback processes have been fully developed.
Aims. We aim to investigate if there is a connection between the presence of strong HCN-vib emission and the development of feedback in (ultra)luminous infrared galaxies ((U)LIRGs).
Methods. We collected literature and archival data to compare the luminosities of rotational lines of HCN-vib, normalized to the total infrared luminosity, to the median velocities of 119 μm OH absorption lines, potentially indicating outflows, in a total of 17 (U)LIRGs.
Results. The most HCN-vib luminous systems all lack signatures of significant molecular outflows in the far-infrared OH absorption lines. However, at least some of the systems with bright HCN-vib emission have fast and collimated outflows that can be seen in spectral lines at longer wavelengths, including in millimeter emission lines of CO and HCN (in its vibrational ground state) and in radio absorption lines of OH.
Conclusions. We conclude that the galaxy nuclei with the highest LHCN − vib/LIR do not drive wide-angle outflows that are detectable using the median velocities of far-infrared OH absorption lines. This is possibly because of an orientation effect in which sources oriented in such a way that their outflows are not along our line of sight also radiate a smaller proportion of their infrared luminosity in our direction. It could also be that massive wide-angle outflows destroy the deeply embedded regions responsible for bright HCN-vib emission, so that the two phenomena cannot coexist. This would strengthen the idea that vibrationally excited HCN traces a heavily obscured stage of evolution before nuclear feedback mechanisms are fully developed.
Latitudinal differential rotation in the solar analogues 16 Cygni A and B
Authors: Bazot M. , Benomar O. , Christensen-Dalsgaard J. , Gizon L. , Hanasoge S. , Nielsen M. , Petit P. , Sreenivasan K. R. 
Published: January 2019

Context.Asteroseismology has undergone a profound transformation as a scientific field following the CoRoT andKeplerspace missions. The latter is now yielding the first measurements of latitudinal differential rotation obtained directly from oscillation frequencies. Differential rotation is a fundamental mechanism of the stellar dynamo effect.Aims.Our goal is to measure the amount of differential rotation in the solar analogues 16 Cyg A and B, which are the components of a binary system. These stars are the brightest observed byKeplerand have therefore been extensively observed, with exquisite precision on their oscillation frequencies.Methods.We modelled the acoustic power spectrum of 16 Cyg A and B using a model that takes into account the contribution of differential rotation to the rotational frequency splitting. The estimation was carried out in a Bayesian setting. We then inverted these results to obtain the rotation profile of both stars under the assumption of a solar-like functional form.Results.We observe that the magnitude of latitudinal differential rotation has a strong chance of being solar-like for both stars, their rotation rates being higher at the equator than at the pole. The measured latitudinal differential rotation, defined as the difference of rotation rate between the equator and the pole, is 320 ± 269 nHz and 440−383+363nHz for 16 Cyg A and B, respectively, confirming that the rotation rates of these stars are almost solar-like. Their equatorial rotation rates are 535 ± 75 nHz and 565−129+150nHz. Our results are in good agreement with measurements obtained from spectropolarimetry, spectroscopy, and photometry.Conclusions.We present the first conclusive measurement of latitudinal differential rotation for solar analogues. Their rotational profiles are very close to those of the Sun. These results depend weakly on the uncertainties of the stellar parameters.
De-novo-Auftreten einer Vitiligo unter IL-12/23-Inhibitor-Therapie einer chronischen Plaque-Psoriasis
Authors: Troyanova-Slavkova S. , Kowalzick L. 
Published: January 2019

ZusammenfassungWir berichten über einen 54-jährigen männlichen Patienten mit seit über 13 Jahren bestehender chronischer Plaque-Psoriasis und metabolischem Syndrom, der über 5 Jahre nach Beginn einer s. c. Therapie mit einem Interleukin-12/23-Inhibitor (Ustekinumab) eine Vitiligo in den seitlichen Gesichtspartien entwickelte. Vier Monate zuvor wurde wegen eines neu diagnostizierten Diabetes mellitus Typ 2 eine s. c. Insulin-Therapie begonnen. Das Neuauftreten einer Vitiligo als paradoxe Reaktion auf eine Biologika-Therapie mit TNF-alpha-, Interleukin-12/23- und Interleukin-17-Inhibitoren wurde bisher in nur wenigen Einzelfällen beschrieben, ein Zusammenhang mit einer Insulin-Therapie meist nur bei autoimmunologisch bedingtem Typ-1-Diabetes.
Effektivität und Risiken der tiefen lateralen knöchernen Orbitadekompression mit Entfernung der Orbitakante bei endokriner Orbitopathie
Authors: Horn Maren , Schittkowski Michael 
Published: January 2019

Zusammenfassung
Hintergrund Die endokrine Orbitopathie ist die häufigste extrathyroidale Manifestation einer Autoimmunthyreopathie. In der ausgebrannten fibrotischen Phase können ein Exophthalmus, Doppelbilder und eine Lidretraktion zurückbleiben, die ggf. mehrere rehabilitative chirurgische Eingriffe erfordern. Die orbitale Dekompression ist ein etabliertes Verfahren in der operativen Therapie der endokrinen Orbitopathie, um einen Exophthalmus zu reduzieren. Ziel der Arbeit war, die Technik der tiefen lateralen knöchernen Orbitadekompression mit Entfernung der Orbitakante in Hinblick auf Effektivität und Komplikationen zu evaluieren.
Patienten und Methoden In einer retrospektiven Fallserie wurden alle zwischen 2008 und 2015 in der Augenklinik der Universitätsmedizin Göttingen durchgeführten Dekompressionsoperationen in Hinblick auf Exophthalmusreduktion, Diplopie (Gorman Score) sowie Komplikationen analysiert. Die OP-Technik umfasste die Entfernung der lateralen Orbitawand (Ausmaß und Tiefe individuell angepasst) sowie (partiell) des extrakonalen Fettgewebes über einen Hautschnitt im lateralen Lidwinkel („swinging eyelid approach“).
Ergebnisse 195 Dekompressionsoperationen an 127 Patienten wurden eingeschlossen. Die mittlere Exophthalmusreduktion betrug 4,0 ± 1,2 mm (Min. 1,5; Max. 7,5 mm). Bei 47 Patienten (37,0%)/77 Operationen (39,5%) bestand präoperativ keine Diplopie. Postoperativ wurde bei 3 dieser Patienten/3 Orbitae (6,4/3,9%) eine „new-onset“-Diplopie dokumentiert (2,4% aller Patienten, 1,5% aller Operationen). Einer der 3 Patienten hatte Doppelbilder in Primärposition (0,8% aller Patienten, 2,1% der Patienten ohne präoperative Diplopie), die 2 weiteren Patienten gaben blickrichtungsabhängige Doppelbilder an. Eine postoperative Verbesserung der Doppelbilder zeigte sich bei 19 Patienten (15,0% aller Patienten, 23,8% der Patienten mit präoperativen Doppelbildern) bzw. nach 19 Operationen (9,7% aller 195 Eingriffe, 16,1% der Fälle mit präoperativer Diplopie). Bis auf eine starke postoperative Blutung in einem Fall, die chirurgisch erfolgreich und folgenlos saniert werden konnte, traten keine schwerwiegenden Komplikationen auf. Dokumentiert wurden eine sichtbare Narbenbildung in 6 Fällen (3,1%), eine temporale Einziehung in 3 Fällen (1,5%), Oszillopsien beim Kauen in 3 Fällen (1,5%) und eine Desinsertion der lateralen Kanthusregion in 2 Fällen (1%).
Schlussfolgerung Die tiefe laterale knöcherne Orbitadekompression unter Einschluss des vorderen Orbitarandes stellt eine sichere und effektive Methode zur Reduktion des Exophthalmus bei endokriner Orbitopathie dar.
Ambulante Nachsorge nach stationärer Adipositasrehabilitation: Machbarkeit des KgAS-Nachsorgekonzeptes
Authors: Pankatz M. , Gellhaus I. , Hagedorn N. , Hampel P. , Tiedjen U. , Stachow R. 
Published: January 2019

ZusammenfassungRehabilitationsmaßnahmen für Kinder und Jugendliche mit Adipositas sind kurzfristig sehr erfolgreich, die Rückfallrate ist jedoch hoch. Nachsorgeprogramme hatten in Wirksamkeitsstudien keinen nachweisbaren Erfolg oder wurden eingestellt. Die Konsensusgruppe Adipositasschulung für Kinder und Jugendliche (KgAS) hat daher ein neues Programm entwickelt, das in einer Machbarkeitsstudie evaluiert wurde. In Kooperation der Fachklinik Sylt für Kinder und Jugendliche der DRV Nord mit ambulanten Partnern wurde 25 Familien die Teilnahme ermöglicht. Während des stationären Aufenthaltes des Kindes wurden sie in eine anschließende ambulante Nachsorge am Heimatort vermittelt. Die Teilnahme wurde durch eine Fragebogenerhebung (Eltern, Kinder/Jugendliche, Nachsorgekräfte) begleitet, außerdem wurden Einzelgespräche und ein Fokusgruppeninterview mit den Nachsorgekräften ausgewertet. Die Auswertung zeigte eine gute Machbarkeit und hohe Zufriedenheitswerte bei allen beteiligten Gruppen (Kinder/Jugendliche, Eltern, Nachsorgekräfte, Rehabilitationsklinik). Somit scheint der Nachsorgeansatz der KgAS geeignet, in das Regelangebot der Behandlung überführt zu werden. Zukünftig muss jedoch eine randomisiert-kontrollierte Studie die Wirksamkeit überprüfen.
α-Tetralonyl Glucosides from the Green Walnut Husks of Juglans mandshurica and Their Antiproliferative Effects
Authors: Wang An-dong , Xie Chao-jie , Zhang Yun-qiang , Li Mei-chen , Wang Xia , Liu Jian-yu , Xu Yong-nan 
Published: January 2019

AbstractTwo new α-tetralonyl glucosides, (4S)-4,5,8-trihydroxy-α-tetralone-5-O-β-D-glucopyranosyl(1 → 6)-β-D-glucopyranoside (1) and (4S)-4,8-dihydroxy-α-tetralone-4-O-β-D-glucopyranosyl(1 → 6)-β-D-glucopyranoside (2), together with eight known compounds (3 – 10) were isolated from the green walnut husks of Juglans mandshurica. The structural characterization of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR and HR-ESI-MS experiments. The isolated compounds were assayed for their cytotoxicity against two human cancer cell lines, A549 and HeLa. Four compounds (7 – 10) exhibited inhibitory effects against two human cancer cell lines with GI50 values between 1.3 and 5.8 µM.
Common Risk Factors Add to Inherited Thrombophilia to Predict Venous Thromboembolism Risk in Families
Authors: Suchon Pierre , Resseguier Noemie , Ibrahim Manal , Robin Alexia , Venton Geoffroy , Barthet Marie-Christine , Brunet Dominique , Saut Noemie , Alessi Marie-Christine , Trégouët David , Morange Pierre 
Published: January 2019

AbstractThe clinical venous thromboembolism (VTE) pattern often shows wide heterogeneity within relatives of a VTE-affected family, although they carry the same thrombophilia defect. It is then mandatory to develop additional tools for assessing VTE risk in families with thrombophilia. This study aims to assess whether common environmental and genetic risk factors for VTE contribute to explain this heterogeneity. A total of 2,214 relatives from 651 families with known inherited thrombophilia were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2013. A thrombophilia screening was systematically performed in all included relatives. According to the severity of the thrombophilia defect, individuals were split into three groups: no familial defect, mild thrombophilia, and severe thrombophilia. In addition, common genetic factors (ABO blood group and 11 polymorphisms selected on the basis of their association with VTE in the general population) were genotyped. Furthermore, body mass index and smoking were collected. VTE incidence was 1.74, 3.64, and 6.40 per 1,000 person-years in individuals with no familial defect, mild thrombophilia, and severe thrombophilia, respectively. Five common risk factors were associated with VTE in this population: obesity, smoking, ABO blood group, and F11_rs2036914 and FGG_rs2066865 polymorphisms. These common factors were then included into a three-level risk score. The score was highly efficient for assessing VTE risk in mild thrombophilia patients by identifying two groups with different VTE risk; individuals with low score had the same risk as individuals with no familial defect whereas individuals with high score had the same risk as individuals with severe thrombophilia. An overall score including the five items plus the thrombophilia status was built and displayed an area under the receiver operating characteristic curve of 0.702 for discriminating VTE and non-VTE relatives. In conclusion, integrating common environmental and genetic risk factors improved VTE risk assessment in relatives from families with thrombophilia.
The effects of students’ self-regulation on translation quality
Authors: Pietrzak Paulina 
Published: January 2019

Abstract
The article is an attempt to enter into the area of metacognitive translation studies – or metacognitive translator studies – that has so far received scant coverage, and devote closer attention to the translator’s self-regulatory activity. Self-regulation seems crucial in the development of translation expertise, “especially outside of optimally structured work environments, training academies, and other places with defined translation workflows and opportunities for feedback” (Shreve 2006: 32). The article focuses on the role and nature of self-regulation in translator training. Having identified the issues that emerge from educational theories for translator training, the author analyses the approaches to metacognition in the area of translation education. In an attempt to contribute to the discussion of the multifaceted nature of translator competence, the author investigates the correlation between translation trainees’ self-regulatory activity and the quality of their translation as reflected in their translation grades.
The use of stance markers in West African Englishes
Authors: Gut Ulrike , Unuabonah Foluke 
Published: January 2019

Abstract
This chapter investigates the extent of similarity in the use of stance markers in two national varieties of West African English, Nigerian English and Ghanaian English, and compares them to British English. The frequency and stylistic variability of four semantic groups of stance markers were examined in ICE-Nigeria and ICE-Ghana and compared with ICE-Great Britain. The results are mixed: the two West African varieties show an overall lower frequency of stance markers compared to British English but the speakers of the two West African English varieties do not demonstrate lower stylistic variability in the use of stance markers across different text types. Notwithstanding, there are systematic differences in stance marker usage between the two West African English varieties.
A corpus-based analysis of conjunctive cohesion in English essays of Nigerian university learners
Authors: Iyabo Adeyemi 
Published: January 2019

Abstract
The study examines the use of conjunctions in written texts by Nigerian university learners. It uses the corpus-based method and instruments to compare the Nigerian Learner English Corpus (NLEC)’s use of conjunctions to their native counterparts in Louvain Corpus of Native English Essays (LOCNESS). The analysis shows additive conjunctions have the highest frequency of use by the two learner groups, while causal, adversative and temporal conjunctions have below average usage. The learners repeatedly used particular conjunctions and underused others within the same category. The study concludes that the advanced learners do not display the optimal awareness of the various alternative conjunctive items available within the different groups to create stylistic variation in their texts for enhanced cohesion and overall coherence.
African corpora for standards in African academic English
Authors: Schmied Josef 
Published: January 2019

Abstract
This contribution proposes to replace the traditional native-speaker model at African universities with a sophisticated and stratified corpus model of nation-, university- and department-specific usage. It illustrates that the long-discussed realistic “national standard” may be possible – at least for restricted domains at advanced levels such as postgraduate studies. A qualitative and quantitative analysis of prepositions and their variation in three case studies shows that there is some flexibility in preposition usage: cases where different preposition choices can be explained by equally valid cognitive principles, cases where the addition of prepositions may be acceptable because this adds explicitness (which may be preferred in non-native contexts) and cases where prepositions may appear redundant since there is no choice and no semantic opposition. Although sociolinguistic values and attitudes may be necessary complements to linguistic frequency analyses, a careful corpus-linguistic study of prepositional choices irrespective of standardised native conventions is the basis for all discussions of new functional standards for African English.