bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humanization of Antibodies using a Statistical Inference Approach
Authors: Clavero-Álvarez Alejandro , Di Mambro Tomas , Perez-Gaviro Sergio , Magnani Mauro , Bruscolini Pierpaolo 
Published: September 2018

AbstractAntibody humanization is a key step in the preclinical phase of the development of therapeutic antibodies, originally developed and tested in non-human models (most typically, in mouse). The standard technique of Complementarity-Determining Regions (CDR) grafting into human Framework Regions of germline sequences has some important drawbacks, in that the resulting sequences often need further back-mutations to ensure functionality and/or stability. Here we propose a new method to characterize the statistical distribution of the sequences of the variable regions of human antibodies, that takes into account phenotypical correlations between pairs of residues, both within and between chains. We define a “humanness score” of a sequence, comparing its performance in distinguishing human from murine sequences, with that of some alternative scores in the literature. We also compare the score with the experimental immunogenicity of clinically used antibodies. Finally, we use the humanness score as an optimization function and perform a search in the sequence space, starting from different murine sequences and keeping the CDR regions unchanged. Our results show that our humanness score outperforms other methods in sequence classification, and the optimization protocol is able to generate humanized sequences that are recognized as human by standard homology modelling tools.
Fast robust dose calculation on GPU for high-precision 1H, 4He, 12C and 16O ion therapy: the FRoG platform
Authors: Mein Stewart , Choi Kyungdon , Kopp Benedikt , Tessonnier Thomas , Bauer Julia , Ferrari Alfredo , Haberer Thomas , Debus Jürgen , Abdollahi Amir , Mairani Andrea 
Published: September 2018

AbstractRadiotherapy with protons and heavier ions landmarks a novel era in the field of high-precision cancer therapy. To identify patients most benefiting from this technologically demanding therapy, fast assessment of comparative treatment plans utilizing different ion species is urgently needed. Moreover, to overcome uncertainties of actual in-vivo physical dose distribution and biological effects elicited by different radiation qualities, development of a reliable high-throughput algorithm is required. To this end, we engineered a unique graphics processing unit (GPU) based software architecture allowing rapid and robust dose calculation. FRoG, Fast Recalculation on GPU, currently operates with four particle beams available at Heidelberg Ion Beam Therapy center, i.e., raster-scanning proton (1H), helium (4He), carbon (12C) and oxygen ions (16O). FRoG enables comparative analysis of different models for estimation of physical and biological effective dose in 3D within minutes and in excellent agreement with the gold standard Monte Carlo (MC) simulation. This is a crucial step towards development of next-generation patient specific radiotherapy.
Activation of oxytocin neurons in the paraventricular nucleus drives cardiac sympathetic nerve activation following myocardial infarction in rats
Authors: Roy Ranjan K. , Augustine Rachael A. , Brown Colin H. , Schwenke Daryl O. 
Published: September 2018

AbstractMyocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (SNA) that facilitates potentially fatal arrhythmias. The mechanism(s) underpinning sympathetic activation remain unclear. Some neuronal populations within the hypothalamic paraventricular nucleus (PVN) have been implicated in SNA. This study elucidated the role of the PVN in triggering cardiac SNA following MI (left anterior descending coronary artery ligation). By means of c-Fos, oxytocin, and vasopressin immunohistochemistry accompanied by retrograde tracing we showed that MI activates parvocellular oxytocin neurons projecting to the rostral ventral lateral medulla. Central inhibition of oxytocin receptors using atosiban (4.5 µg in 5 µl, i.c.v.), or retosiban (3 mg/kg, i.v.), prevented the MI-induced increase in SNA and reduced the incidence of ventricular arrhythmias and mortality. In conclusion, pre-autonomic oxytocin neurons can drive the increase in cardiac SNA following MI and peripheral administration of an oxytocin receptor blocker could be a plausible therapeutic strategy to improve outcomes for MI patients.
Fully‐integrated high‐speed IM for improving high‐power marine engines
Authors: Gerada David , Xu Zeyuan , Huang Xuzhen , Gerada Chris 
Published: September 2018

In this study, electrical machine technologies are compared comprehensively for a hybrid turbocharger used with a high‐power marine engine. It is required for the machine to operate in a thermally aggressive environment, with turbine exhaust temperatures in excess of 600°C. Furthermore, it is required to both generate from the extra exhaust energy (turbo‐compounding) at high‐engine loads as well as a motor for low‐engine loads during slow steaming. The application investigated translates to a machine featuring both high‐power (150 kW) and high speeds (25–50 krpm), together with a considerable constant power–speed region. In this study, induction machines (IM), permanent magnet machines and switched reluctance machines are compared taking into account a number of aspects including the thermal performance, torque ripple, converter volt–ampere rating, and cost. In light of the technical and market requirements, the IM featuring new materials is prototyped and tested for the application in a representative environment.
Improving organic solar cell efficiency using solution processed poly (3‐hexylthiophene) buffer layer
Authors: Ghosekar Ishan C. , Patil Ganesh C. 
Published: September 2018

In this work, it has been shown that inserting buffered poly 3‐hexylthiophene layer between hole transport layer and blended polymer: fullerene active layer of the organic solar cell (OSC) improves the power conversion efficiency by 34% over the conventional OSC. The buffer layer also increases short‐circuit current density from 4.97 ± 0.2 mA/cm2 (without buffer layer) to 6.12 ± 0.3 mA/cm2 (with buffer layer). These improvements are mainly due to increased absorption in the buffered polymer layer. The buffer layer insertion leads to better charge carrier collection and lesser hole recombination at the hole transport interface, which increases shunt resistance and reduces the series resistance of the device. In addition, the insertion of the buffer layer also shows significant improvement in the absorbance spectrum and external quantum efficiency of the device.
Detection of magnetic fields in He-rich early B-type stars using HARPSpol
Authors: Järvinen S. P. , Hubrig S. , Ilyin I. , Schöller M. , Nieva M. F. , Przybilla N. , Castro N. 
Published: September 2018

Aims. We focus on early-B type stars with helium overabundance, for which the presence of a magnetic field has not previously been reported.
Methods. The measurements were carried out using high-spectral-resolution spectropolarimetric observations obtained with the High Accuracy Radial velocity Planet Searcher (HARPS) in polarimetric mode, installed at the ESO La Silla 3.6 m telescope.
Results. For five He-rich stars, the longitudinal magnetic field was detected for the first time. For one target, HD 58260, the presence of a longitudinal magnetic field of the order of 1.8 kG has already been reported in the literature, but the magnetic field has remained constant over tens of years. Our measurement carried out using the polarimetric spectra obtained in 2015 March indicates a slight decrease of the longitudinal magnetic field strength compared to measurements reported in previous works. A search for periodic modulation in available photometric data allowed us to confidently establish a period of 2.64119 ± 0.00420 d in archival ASAS3 data for CPD–27°1791. No period could be determined for the other five stars.
Conclusions. The obtained results support the scenario that all He-rich stars are detectably magnetic and form an extension of the Ap star phenomenon to higher temperatures.
Analysis of unresolved photospheric magnetic field structure using Fe I 6301 and 6302 lines
Authors: Gordovskyy M. , Shelyag S. , Browning P. K. , Lozitsky V. G. 
Published: September 2018

Context.Early magnetographic observations indicated that the magnetic field in the solar photosphere has an unresolved small-scale structure. Near-infrared and optical data with extremely high spatial resolution show that these structures have scales of a few tens of kilometres, which are not resolved in the majority of solar observations.
Aims.The goal of this study is to establish the effect of the unresolved photospheric magnetic field structure on Stokes profiles observed with relatively low spatial resolution. Ultimately, we aim to develop methods for fast estimation of the photospheric magnetic filling factor and line-of-sight gradient of the photospheric magnetic field, which can be applied to large observational data sets.
Methods.We exploit 3D magnetohydrodynamic models of magneto-convection developed using the MURAM code. Corresponding profiles of Fe I 6301.5 and 6302.5 Å spectral lines are calculated using the NICOLE radiative transfer code. The resulting I and V Stokes [x, y, λ] cubes with a reduced spatial resolution of 150 km are used to calculate magnetic field values as they would be obtained in observations with the Solar Optical Telescope (SOT) onboard Hinode or the Helioseismic and Magnetic Imager (HMI) onboard the Solar Dynamic Observatory (SDO) mission.
Results. Three different methods of magnetic filling factor estimation are considered: the magnetic line ratio method, the Stokes V width method, and a simple statistical method. We find that the statistical method and the Stokes V width method are sufficiently reliable for fast filling factor estimations. Furthermore, we find that the Stokes I ± V bisector splitting gradient can be used for fast estimation of the line-of-sight gradient of the photospheric magnetic field.
Core-collapse supernovae in the hall of mirrors
Authors: Cabezón Rubén M. , Pan Kuo-Chuan , Liebendörfer Matthias , Kuroda Takami , Ebinger Kevin , Heinimann Oliver , Perego Albino , Thielemann Friedrich-Karl 
Published: September 2018

Context. Modeling core-collapse supernovae (SNe) with neutrino transport in three dimensions (3D) requires tremendous computing resources and some level of approximation. We present a first comparison study of core-collapse SNe in 3D with different physics approximations and hydrodynamics codes.
Aims. The objective of this work is to assess the impact of the hydrodynamics code, approximations for the neutrino, gravity treatments, and rotation on the simulation of core-collapse SNe in 3D.
Methods. We use four different hydrodynamics codes in this work (ELEPHANT, FLASH, fGR1, and SPHYNX) in combination with two different neutrino treatments, the isotropic diffusion source approximation (IDSA) and two-moment M1, and three different gravity treatments (Newtonian, 1D General Relativity correction, and full General Relativity). Additional parameters discussed in this study are the inclusion of neutrino-electron scattering via a parametrized deleptonization and the influence of rotation.
Results. The four codes compared in this work include Eulerian and fully Lagrangian (smoothed particle hydrodynamics) codes for the first time. They show agreement in the overall evolution of the collapse phase and early post-bounce within the range of 10% (20% in some cases). The comparison of the different neutrino treatments highlights the need to further investigate the antineutrino luminosities in IDSA, which tend to be relatively high. We also demonstrate the requirement for a more detailed heavy-lepton neutrino leakage. When comparing with a full General Relativity code, including an M1 transport method, we confirm the influence of neutrino-electron scattering during the collapse phase, which is adequately captured by the parametrized deleptonization scheme. Also, the effective general relativistic potential reproduces the overall dynamic evolution correctly in all Newtonian codes. Additionally, we verify that rotation aids the shock expansion and estimate the overall angular momentum losses for each code in rotating scenarios.
LoTSS DR1: Double-double radio galaxies in the HETDEX field
Authors: Mahatma V. H. , Hardcastle M. J. , Williams W. L. , Best P. N. , Croston J. H. , Duncan K. , Mingo B. , Morganti R. , Brienza M. , Cochrane R. K. , Gürkan G. , Harwood J. J. , Jarvis M. J. , Jamrozy M. , Jurlin N. , Morabito L. K. , Röttgering H. J. A. , Sabater J. , Shimwell T. W. , Smith D. J. B. , Shulevski A. , Tasse C. 
Published: September 2018

Context. Double-double radio galaxies (DDRGs) represent a short but unique phase in the life-cycle of some of the most powerful radio-loud active galactic nuclei (RLAGN). These galaxies display large-scale remnant radio plasma in the intergalactic medium left behind by a past episode of active galactic nuclei (AGN) activity, and meanwhile, the radio jets have restarted in a new episode. The knowledge of what causes the jets to switch off and restart is crucial to our understanding of galaxy evolution, while it is important to know if DDRGs form a host galaxy dichotomy relative to RLAGN.
Aims. The sensitivity and field of view of LOFAR enables the observation of DDRGs on a population basis rather than single-source observations. Using statistical comparisons with a control sample of RLAGN, we may obtain insights into the nature of DDRGs in the context of their host galaxies, where physical differences in their hosts compared to RLAGN as a population may allow us to infer the conditions that drive restarting jets.
Methods. We utilised the LOFAR Two-Metre Sky Survey (LoTSS) DR1, using a visual identification method to compile a sample of morphologically selected candidate DDRGs, showing two pairs of radio lobes. To confirm the restarted nature in each of the candidate sources, we obtained follow-up observations with the Karl. G. Jansky Very Large Array (VLA) at higher resolution to observe the inner lobes or restarted jets, the confirmation of which created a robust sample of 33 DDRGs. We created a comparison sample of 777 RLAGN, matching the luminosity distribution of the DDRG sample, and compared the optical and infrared magnitudes and colours of their host galaxies.
Results. We find that there is no statistically significant difference in the brightness of the host galaxies between double-doubles and single-cycle RLAGN. The DDRG and RLAGN samples also have similar distributions in WISE mid-infrared colours, indicating similar ages of stellar populations and dust levels in the hosts of DDRGs. We conclude that DDRGs and “normal” RLAGN are hosted by galaxies of the same type, and that DDRG activity is simply a normal part of the life cycle of RLAGN. Restarted jets, particularly for the class of low-excitation radio galaxies, rather than being a product of a particular event in the life of a host galaxy, must instead be caused by smaller scale changes, such as in the accretion system surrounding the black hole.
Association of Higher Maternal Serum Levels of Plac1 Protein with Intrauterine Growth Restriction
Authors: Ibanoglu Mujde Can , Ozgu-Erdinc A. Seval , Kara Ozgur , Topcu H. Onur , Uygur Dilek 
Published: September 2018

AbstractThe aim of this study was to determine the maternal PLAC1 protein levels in infants with IUGR. A total of 40 pregnant women with IUGR and 40 controls were recruited in this case control study between June 2014 and November 2014. Maternal serum PLAC1 levels were established as significantly higher in IUGR cases compared to the control groups (8.42±3.59 ng/ml vs. 6.27±4.04 ng/ml, p<0.001). Area under ROC curve (AUC) analysis of PLAC1 in IUGR was 0.708, (95% confidence interval (CI): 0.593–0.823, p=0.001) (Figure 1). Maternal PLAC1 levels above 7.41 ng/ml had a sensitivity of 62.5% (95% C1: 45.81–76.83), a specificity of 77.5% (95% CI: 61.15–88.6); positive and negative predictive values (PPV and NPV) were 73.53% (95% CI: 55.35–86.49) and 67.39% (95% CI: 51.86–80.03), respectively, with a diagnostic accuracy of 70%. In conclusion, we were able to demonstrate a significantly important link between IUGR and higher maternal serum levels of the PLAC1 protein.
Literature-based automated discovery of tumor suppressor p53 phosphorylation and inhibition by NEK2
Authors: Choi Byung-Kwon , Dayaram Tajhal , Parikh Neha , Wilkins Angela D. , Nagarajan Meena , Novikov Ilya B. , Bachman Benjamin J. , Jung Sung Yun , Haas Peter J. , Labrie Jacques L. , Pickering Curtis R. , Adikesavan Anbu K. , Regenbogen Sam , Kato Linda , Lelescu Ana , Buchovecky Christie M. , Zhang Houyin , Bao Sheng Hua , Boyer Stephen , Weber Griff , Scott Kenneth L. , Chen Ying , Spangler Scott , Donehower Lawrence A. , Lichtarge Olivier 
Published: September 2018

SignificanceWe adapted natural language processing to the biological literature and demonstrated end-to-end automated knowledge discovery by exploring subtle word connections. General text mining scanned 21 million publication abstracts and selected a reliable 130,000 from which hypothesis generation algorithms predicted kinases not known to phosphorylate p53, but likely to do so. Six of these p53 kinase candidates passed experimental validation. Among them NEK2 was examined in depth and shown to repress p53 and promote cell division. This work demonstrates the possibility of integrating a vast corpora of written knowledge to compute valuable hypotheses that will often test true and fuel discovery.
Teacher perceptions and use of tasks in school ESL classrooms
Authors: Oliver Rhonda , Bogachenko Tatiana 
Published: September 2018

Although Task-Based Language Teaching (TBLT) is becoming increasingly popular among researchers and practitioners worldwide, teachers’ perceptions about tasks and their use within school classrooms have received scant attention in the literature. Given that perceptions about ‘task’ influence pedagogy, not only in terms of syllabus design, but also with respect to classroom approaches, teaching style, assessment methods and ultimately even learning outcomes, there is a real need to investigate them in the classroom context. This chapter presents findings of a research study with this aim.
Primary and secondary school ESL teachers in Western Australia were surveyed, and written samples of the tasks they use were collected and analyzed to reveal the ways teachers design tasks, define their aims and assess students’ performance. The results indicate that there is little consistency among teachers in relation to these things. The survey data clearly indicates different levels of teacher awareness of TBLT. At the same time, differences in task definition and design by these practitioners might be partially attributed to the inconsistency that exists in the literature itself. The findings are discussed in light of this, and suggestions for pedagogy made.
Researching TBLT for young, beginner learners in Japan
Authors: Shintani Natsuko 
Published: September 2018

This chapter addresses a personal account of how I came to carry out research into TBLT within, and as a response to, my own teaching context. I started my career as an English teacher in a large private language institution. Due to my dissatisfaction with the effectiveness of the teaching methods at the institution, I started my own language school, where I implemented more intensive production-based teaching. However, similar problems emerged in my own school, particularly the failure to develop students’ communicative skills after years of instruction. After studying the literature on second language learning and teaching, I decided to effect a radical change in my teaching method: employing task-based language teaching (TBLT). My first attempt to use tasks with experienced students succeeded. However, to implement TBLT in a classroom with young beginning learners, I realized that I needed a more specialized approach. After reviewing the literature on tasks with absolute beginners, I decided to design input-based tasks. While the students clearly enjoyed the tasks, at that point I was still uncertain about their effectiveness, especially given the lack of immediate language production by the students. This led me to conduct experimental research investigating the effectiveness of this approach compared to the traditional one I used to use – presentation-practice-production (PPP).
The chapter starts with a brief overview of my teaching context – English education for young learners in Japan. Then, I provide a personal account of my journey as an English teacher and my attempts to conduct research in my own teaching context, notably my struggle with effective research design. My hope is that my story will provide an example of how it is possible for a teacher to conduct research to resolve classroom issues or to confirm a teaching approach in a given teaching context.
Achieving impact: impact evaluations and narrative simplification
Authors: Hellström Tomas , Hellström Christina 
Published: September 2018

ABSTRACT
This study is concerned with how impact from research and innovation (R&I) programmes is accounted for in impact evaluation reports. Establishing causal links between a research funding instrument and different effects, poses well known methodological difficulties. In the light of such challenges, textual accounts about causal links ought to be carefully written. Nevertheless, impact evaluation reports have a tendency towards unwarranted simplification as far as impact inferences are concerned. In this study, we illustrate how such simplifications – versions of the narrative device ellipsis – are accomplished. Using examples from three Swedish impact evaluation reports, we focus on the constituent components of longer impact accounts, that of the impact argument, to analyze the various ways that impact is narratively achieved through simplification. We believe this analysis can contribute to the methodology of impact evaluation, as well as spread light on some the difficulties in the historiography of innovation in general.
Vestibular findings in patients with schwannoma of the 8th cranial nerve
Authors: Palma Silvia , Boldrini Paola , Genovese Elisabetta , Auletta Gennaro , Martini Alessandro , Cenacchi Giovanna 
Published: September 2018

Introduction:
Some aspects of the natural history of vestibular schwannoma (VS) remain unsettled. A better understanding of the pathophysiology of the disease would improve its diagnostic workup and therapeutic management, as VS often requires surgery, which carries the risk of severe complications. This paper discusses the significance of ultrastructural findings in the vestibular organs removed during surgery.

Material and methods:
This study examined specimens from vestibular organs removed from patients who underwent VS resection through the translabyrinthine approach. The sample includes 9 patients, seven women and two men, with a mean age of 55 years (range 39–71 years).

Results:
The sensory epithelium showed a loss of stereocilia, numerous lipofuscin granules and vacuoles in the cytoplasm. The subepithelial myelinated nerve fibres showed signs of demyelination and sheath rearrangement. Some axons had markedly degenerative modifications, with neurofilament aggregation, more numerous mitochondria and vacuolization. As it lost its specialized structures, the epithelial covering of the semicircular canal walls progressively flattened out in the area farthest away from the sensorial area.

Conclusions:
There were no specific correlations between schwannoma size and instrumental or ultrastructural findings in the vestibular epithelium organs. The morphological features of the non-sensory epithelium suggest that the potassium circulation system is preserved in patients with VS even when they present prominent cochlear and/or vestibular symptoms. VS formation appears to be multifactorial; the vestibular nerve conduction block caused by tumour compression would not necessarily cause irreversible damage to the vestibular receptors at the outset.