bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the pharmacokinetics of entrectinib and its active M5 metabolite in healthy volunteers and patients with solid tumors
Authors: Meneses-Lorente Georgina , Bentley Darren , Guerini Elena , Kowalski Karey , Chow-Maneval Edna , Yu Li , Brink Andreas , Djebli Nassim , Mercier Francois , Buchheit Vincent , Phipps Alex 
Published: January 2021

SummaryBackground: Entrectinib is an oral, CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, tyrosine kinase ROS proto-oncogene 1, and anaplastic lymphoma kinase approved for use in patients with solid tumors. We describe 3 clinical studies, including one investigating the single/multiple dose pharmacokinetics of entrectinib in patients and two studies in healthy volunteers investigating the absorption/distribution/metabolism/excretion (ADME) of entrectinib, its relative bioavailability, and effect of food on pharmacokinetics. Methods: The patient study is open-label with dose-escalation and expansion phases. Volunteers received entrectinib (100–400 mg/m2, and 600–800 mg) once daily with food in continuous 28-day cycles. In the ADME study, volunteers received a single oral dose of [14C]entrectinib 600 mg. In the third study, volunteers received single doses of entrectinib 600 mg as the research and marketed formulations in the fasted state (Part 1), and the marketed formulation in the fed and fasted states (Part 2). Entrectinib and its major active metabolite M5 were assessed in all studies. Results: Entrectinib was absorbed in a dose-dependent manner with maximum concentrations at ~4 h postdose and an elimination half-life of ~20 h. Entrectinib was cleared mainly through metabolism and both entrectinib and metabolites were eliminated mainly in feces (minimal renal excretion). At steady-state, the M5-to-entrectinib AUC ratio was 0.5 (with 600 mg entrectinib research formulation in patients). The research and marketed formulations were bioequivalent and food had no relevant effect on pharmacokinetics. Conclusions: Entrectinib is well absorbed, with linear PK that is suitable for once-daily dosing, and can be taken with or without food.
The structure and role of lactone intermediates in linkage-specific sialic acid derivatization reactions
Authors: Pongracz Tamas , Verhoeven Aswin , Wuhrer Manfred , de Haan Noortje 
Published: January 2021

AbstractSialic acids occur ubiquitously throughout vertebrate glycomes and often endcap glycans in either α2,3- or α2,6-linkage with diverse biological roles. Linkage-specific sialic acid characterization is increasingly performed by mass spectrometry, aided by differential sialic acid derivatization to discriminate between linkage isomers. Typically, during the first step of such derivatization reactions, in the presence of a carboxyl group activator and a catalyst, α2,3-linked sialic acids condense with the subterminal monosaccharides to form lactones, while α2,6-linked sialic acids form amide or ester derivatives. In a second step, the lactones are converted into amide derivatives. Notably, the structure and role of the lactone intermediates in the reported reactions remained ambiguous, leaving it unclear to which extent the amidation of α2,3-linked sialic acids depended on direct aminolysis of the lactone, rather than lactone hydrolysis and subsequent amidation. In this report, we used mass spectrometry to unravel the role of the lactone intermediate in the amidation of α2,3-linked sialic acids by applying controlled reaction conditions on simple and complex glycan standards. The results unambiguously show that in common sialic acid derivatization protocols prior lactone formation is a prerequisite for the efficient, linkage-specific amidation of α2,3-linked sialic acids, which proceeds predominantly via direct aminolysis. Furthermore, nuclear magnetic resonance spectroscopy confirmed that exclusively the C2 lactone intermediate is formed on a sialyllactose standard. These insights allow a more rationalized method development for linkage-specific sialic derivatization in the future.
Characterization of two cis-acting elements, P1BS and W-box, in the regulation of OsPT6 responsive to phosphors deficiency
Authors: Zhao Qingchun , Luo Zhenzhen , Chen Jiadong , Jia Hongfang , Ai Penghui , Chen Aiqun , Li Yiting , Xu Guohua 
Published: January 2021

AbstractPhosphorus (P) deficiency is one of the major nutrient stresses restricting plant growth. The uptake of P by plants from soil is mainly mediated by the phosphate (Pi) transporters belonging to the PHT1 family. Multiple PHT1 genes from diverse plant species have been shown to be strongly up-regulated upon Pi starvation, however, the underlying mechanisms for the Pi-starvation-induced (PSI) up-regulation have not been well deciphered for most Pi transporter genes. Here, we reported a detailed dissection of the promoter activity of a PSI rice Pi transporter gene OsPT6, using the β-glucuronidase (GUS) reporter gene. OsPT6 promoter could drive GUS expression strongly in both roots and blades of rice plants grown under low P, but not high P. Cis-acting element analysis identified one copy of the P1BS motif and two copies of the W-box motif in OsPT6 promoter. Targeted deletion of the P1BS motif caused almost complete abolition of GUS induction in response to Pi starvation, irrespective of the presence or absence of the W-box motif, Four repeats of the P1BS motif fused to the CaMV35S minimal promoter was sufficient to induce GUS expression responsive to Pi starvation. Targeted deletion of the upstream W-box motif (W1) did not affect the GUS expression activity compared with the full-length OsPT6 promoter, while targeted deletion of the downstream W-box motif (W2) or both of the W-box motifs remarkably reduced the GUS induction rate upon Pi starvation. Our results proposed that the PSI response of OsPT6 was positively regulated by at least two elements, the sole P1BS and the downstream W-box, in its promoter, and the W-box-mediated up-regulation of OsPT6 might be highly dependent on the P1BS motif.
Lights, camera, active! appreciation of active learning predicts positive attitudes towards lecture capture
Authors: Nordmann Emily , Clark Anne , Spaeth Elliott , MacKay Jill R. D. 
Published: January 2021

AbstractMuch has been written about instructor attitudes towards lecture capture, particularly concerning political issues such as opt-out policies and the use of recordings by management. Additionally, the pedagogical concerns of lecturers have been extensively described and focus on the belief that recording lectures will impact on attendance and will reduce interactivity and active learning activities in lectures. However, little work has looked at the relationship between attitudes towards lecture capture and broader conceptions of learning and teaching. In this pre-registered study, we administered the Conceptions of Learning and Teaching scale and a novel lecture capture attitude scale to 159 higher education teachers. We found that appreciation of active learning predicted more positive attitudes towards lecture recordings as an educational support tool, whilst higher teacher-centred scores predicted greater concern about the negative educational impact of recordings. The effects observed were small; however, they are strong evidence against the view that it is instructors who value participatory and active learning that are opposed to lecture capture. Exploratory analyses also suggested that those who did not view recordings as an essential educational resource record fewer of their lectures, highlighting the real-world impact that attitudes can have, and further strengthening the need for staff to be provided with evidence-based guidance upon which to base their teaching practice. Data, analysis code, and the pre-registration are available athttps://osf.io/uzs3t/.
The Impact of Stigma, Autism Label and Wording on the Perceived Desirability of the Online Dating Profiles of Men on the Autism Spectrum
Authors: Brosnan M. , Gavin J. 
Published: January 2021

AbstractThose seeking romantic relations are increasingly using online dating sites, including young men on the autism spectrum. This study presented dating profiles with and without an explicit label of autism and positive or negative wording to 306 ‘females seeking a male partner’. Participants assessed the men’s dating profiles in terms of perceived attractiveness, trustworthiness and desire-to-date. They also completed a questionnaire on their level of stigmatisation of, and familiarity with, autism. An explicit autism label and positive wording positively impacted perceived attractiveness. With positively worded profiles, those with highly stigmatising views reported decreased desire-to-date when an explicit label of autism was present; those with low levels of stigmatising reported increased desire-to-date when an explicit autism label was present.
WIDOCK: a reactive docking protocol for virtual screening of covalent inhibitors
Authors: Scarpino Andrea , Petri László , Knez Damijan , Imre Tímea , Ábrányi-Balogh Péter , Ferenczy György G. , Gobec Stanislav , Keserű György M. 
Published: January 2021

AbstractHere we present WIDOCK, a virtual screening protocol that supports the selection of diverse electrophiles as covalent inhibitors by incorporating ligand reactivity towards cysteine residues into AutoDock4. WIDOCK applies the reactive docking method (Backus et al. in Nature 534:570–574, 2016) and extends it into a virtual screening tool by introducing facile experimental or computational parametrization and a ligand focused evaluation scheme together with a retrospective and prospective validation against various therapeutically relevant targets. Parameters accounting for ligand reactivity are derived from experimental reaction kinetic data or alternatively from computed reaction barriers. The performance of this docking protocol was first evaluated by investigating compound series with diverse warhead chemotypes against KRASG12C, MurA and cathepsin B. In addition, WIDOCK was challenged on larger electrophilic libraries screened against OTUB2 and NUDT7. These retrospective analyses showed high sensitivity in retrieving experimental actives, by also leading to superior ROC curves, AUC values and better enrichments than the standard covalent docking tool available in AutoDock4 when compound collections with diverse warheads were investigated. Finally, we applied WIDOCK for the prospective identification of covalent human MAO-A inhibitors acting via a new mechanism by binding to Cys323. The inhibitory activity of several predicted compounds was experimentally confirmed and the labelling of Cys323 was proved by subsequent MS/MS measurements. These findings demonstrate the usefulness of WIDOCK as a warhead-sensitive, covalent virtual screening protocol.
Viscose‐based porous carbon fibers: improving yield and porosity through optimization of the carbonization process by design of experiment
Authors: Breitenbach Stefan , Unterweger Christoph , Lumetzberger Alexander , Duchoslav Jiri , Stifter David , Hassel Achim Walter , Fürst Christian 
Published: January 2021

AbstractIn this study, the production of porous carbon fibers from viscose fibers was investigated. The effects of final carbonization temperature (600–1000 °C) and heating rate (6–600 °C h−1), which determine the carbonization process, on carbon yield, and specific surface area were investigated using a central composite design. The statistical models found were then used to optimize both the yield and the porosity of the carbonized fibers, which are the most important factors for further use as precursors for activated carbon fibers. Despite the contrary effects, porous carbon fibers with a yield of 21.2% could be produced, which at the same time have a specific surface area of 175 m2 g−1. The fibers produced were also characterized by SEM, FTIR and Raman spectroscopy, XRD and CHNS analysis.
The influence of board members with foreign experience on the timely delivery of financial reports
Authors: Dobija Dorota , Puławska Karolina 
Published: January 2021

AbstractThis study examines the effect of the presence of foreign experts on a company’s board on the important characteristic of high-quality financial reporting: timeliness. We focus on experts with foreign experience (EFEs) who are board members, in the context of a dual board model. The sample is drawn from the population of Polish nonfinancial firms listed on the Warsaw Stock Exchange during 2010–2015. For analysis, we use the generalised method of moments with fixed effects. After controlling for corporate governance and firm characteristics, we find that the presence of EFEs shortens the time necessary to deliver financial reports. Our findings enrich the knowledge on the monitoring role of EFEs in corporate governance, especially in the context of the insider model of corporate governance and a dual board structure. The findings have significant implications for policy formulation and provide evidence that the presence of EFEs on supervisory boards may lead to increased timeliness of financial reporting, thus increasing financial reporting quality.
Velocity and acceleration level inverse kinematic calculation alternatives for redundant manipulators
Authors: Patkó Dóra , Zelei Ambrus 
Published: January 2021

AbstractFor both non-redundant and redundant systems, the inverse kinematics (IK) calculation is a fundamental step in the control algorithm of fully actuated serial manipulators. The tool-center-point (TCP) position is given and the joint coordinates are determined by the IK. Depending on the task, robotic manipulators can be kinematically redundant. That is when the desired task possesses lower dimensions than the degrees-of-freedom of a redundant manipulator. The IK calculation can be implemented numerically in several alternative ways not only in case of the redundant but also in the non-redundant case. We study the stability properties and the feasibility of a tracking error feedback and a direct tracking error elimination approach of the numerical implementation of IK calculation both on velocity and acceleration levels. The feedback approach expresses the joint position increment stepwise based on the local velocity or acceleration of the desired TCP trajectory and linear feedback terms. In the direct error elimination concept, the increment of the joint position is directly given by the approximate error between the desired and the realized TCP position, by assuming constant TCP velocity or acceleration. We investigate the possibility of the implementation of the direct method on acceleration level. The investigated IK methods are unified in a framework that utilizes the idea of the auxiliary input. Our closed form results and numerical case study examples show the stability properties, benefits and disadvantages of the assessed IK implementations.
Computational limitations of affine automata and generalized affine automata
Authors: Hirvensalo Mika , Moutot Etienne , Yakaryılmaz Abuzer 
Published: January 2021

AbstractWe present new results on the computational limitations of affine automata (AfAs). First, we show that using the endmarker does not increase the computational power of AfAs. Second, we show that the computation of bounded-error rational-valued AfAs can be simulated in logarithmic space.
Third, we identify some logspace unary languages that are not recognized by algebraic-valued AfAs. Fourth, we show that using arbitrary real-valued transition matrices and state vectors does not increase the computational power of AfAs in the unbounded-error model. When focusing only the rational values, we obtain the same result also for bounded error. As a consequence, we show that the class of bounded-error affine languages remains the same when the AfAs are restricted to use rational numbers only.
Understanding Early Childhood Science Education: Comparative Analysis of Australian and Finnish Curricula
Authors: Havu-Nuutinen Sari , Kewalramani Sarika , Veresov Nikolai , Pöntinen Susanna , Kontkanen Sini 
Published: January 2021

AbstractThis research is a comparative study of Finnish and Australian science curricula in early childhood education (EC). The study aims to figure out the constructivist components of the science curriculum in two countries as well as locate the similarities and differences in the rationale and aims, contents, learning outcomes, learning activities, teacher’s role and assessment. The curriculum analysis framework developed by Van den Akker (2003) was used as a methodological framework for the curricula analysis. Based on the theory-driven content analyses, findings show that both countries have several components of constructivist curriculum, but not always clearly focused on science education. The Australian Early Years Learning Framework (EYLF) integrates children’s science learning within their five specific learning outcomes, whereas the Finnish national core curriculum for early childhood education and care has no defined learning outcomes in general. The Finnish curriculum more clearly than EYLF encompasses science and environmental education as a learning domain, within which children participate in targeted scientific activities to gain procedural knowledge in specific environmental-related concepts. More focus should be turned to the teachers’ role and assessment, which are not determined in science context in both countries. This international comparative study calls for the need of a considered EC curriculum framework that more explicitly has science domains with specifically defined rationale, aims, content areas, learning outcomes and assessment criteria. The implications lie in providing early childhood educators with tangible and theoretically solid curriculum framework and resources in order to foster scientific thinking in young children.
Sulfur Ice Astrochemistry: A Review of Laboratory Studies
Authors: Mifsud Duncan V. , Kaňuchová Zuzana , Herczku Péter , Ioppolo Sergio , Juhász Zoltán , Kovács Sándor T. S. , Mason Nigel J. , McCullough Robert W. , Sulik Béla 
Published: January 2021

AbstractSulfur is the tenth most abundant element in the universe and is known to play a significant role in biological systems. Accordingly, in recent years there has been increased interest in the role of sulfur in astrochemical reactions and planetary geology and geochemistry. Among the many avenues of research currently being explored is the laboratory processing of astrophysical ice analogues. Such research involves the synthesis of an ice of specific morphology and chemical composition at temperatures and pressures relevant to a selected astrophysical setting (such as the interstellar medium or the surfaces of icy moons). Subsequent processing of the ice under conditions that simulate the selected astrophysical setting commonly involves radiolysis, photolysis, thermal processing, neutral-neutral fragment chemistry, or any combination of these, and has been the subject of several studies. The in-situ changes in ice morphology and chemistry occurring during such processing are often monitored via spectroscopic or spectrometric techniques. In this paper, we have reviewed the results of laboratory investigations concerned with sulfur chemistry in several astrophysical ice analogues. Specifically, we review (i) the spectroscopy of sulfur-containing astrochemical molecules in the condensed phase, (ii) atom and radical addition reactions, (iii) the thermal processing of sulfur-bearing ices, (iv) photochemical experiments, (v) the non-reactive charged particle radiolysis of sulfur-bearing ices, and (vi) sulfur ion bombardment of and implantation in ice analogues. Potential future studies in the field of solid phase sulfur astrochemistry are also discussed in the context of forthcoming space missions, such as the NASA James Webb Space Telescope and the ESA Jupiter Icy Moons Explorer mission.
Investigative Interviews with Suspects and Witnesses: A Survey of Perceptions and Interview Practices Among Malaysian Police
Authors: Chung Kai Li , Ng Magdalene , Ding I Ling 
Published: January 2021

AbstractInterviewing of suspects, victims, and eyewitnesses contributes significantly to the investigation process. While a great deal is known about the investigative interviewing practices in the United Kingdom and the Nordic region, very little is known about the framework used by Malaysian police officers. A survey was administered to 44 Royal Malaysian Police interviewers serving in the Sexual, Women and Child Investigations Division (D11) of the Crime Investigation Department. Respondents were asked about the investigative interviewing techniques they use with suspects, witnesses, and victims; how effective they think these techniques are; and the training they had received. Findings revealed that many police officers currently possess limited knowledge of best practice investigative interviewing. More training, feedback, and supervision is needed and desired.
Longitudinal association between autistic traits and affinity for hikikomori in Japanese university students
Authors: Shimono Yuuki , Hasegawa Akira , Tsuchihara Kohei , Tanaka Keisuke , Matsuda Yuko , Kunisato Yoshihiko 
Published: January 2021

AbstractThe affinity for hikikomori represents the desire to be withdrawn, as well as to entertain an empathetic attitude towards withdrawn individuals. It is composed of two subdimensions, the maladaptive desire for hikikomori, and empathy for others with hikikomori. This longitudinal study examined whether autistic traits predicted the affinity for hikikomori. At the baseline assessment, undergraduate and graduate students in Japan (N = 272) completed the Autism-Spectrum Quotient (AQ), the Affinity for Hikikomori Scale in University Students, and measures assessing academic failures and interpersonal conflicts. They also completed all measures excluding the AQ eight weeks later. Structural equation modeling indicated that difficulties in social interaction aspects of autistic traits were positively associated with academic failures at Time 2 even after controlling for academic failures at Time 1. In addition, difficulties in social interaction were positively related to the desire for hikikomori at Time 2 indirectly via academic failures at Time 2 after controlling for the desire for hikikomori at Time 1. Difficulties in social interaction were also directly associated with the increased desire for hikikomori at Time 2. These findings suggest that autistic traits, and especially difficulties in social interaction, are predictors of the maladaptive aspect of the affinity for hikikomori.
Computation of subsurface drain spacing in the unsteady conditions using Artificial Neural Networks (ANN)
Authors: Ostad-Ali-Askari Kaveh , Shayannejad Mohammad 
Published: January 2021

AbstractArtificial neural networks are a tool for modeling of nonlinear systems in various engineering fields. These networks are effective tools for modeling the nonlinear systems. Each artificial neural network includes an input layer, an output layer between which there are one or some hidden layers. In each layer, there are one or several processing elements or neurons. The neurons of the input layer are independent variables of the understudy issue, and the neurons of the output layer are its dependent variables. Artificial neural system, through exerting weight on inputs and by suing an activation function attempts to achieve a desirable output. In this research, in order to calculate the drain spacing in an unsteady state in a region situated in the north east of Ahwaz, Iran with different soil properties and drain spacing, the artificial neural networks have been used. The neurons in the input layer were: Specific yield, hydraulic conductivity, depth of the impermeable layer, height of the water table in the middle of the interval between the drains in two-time steps. The neurons in output layer were drain spacing. The network designed in this research was included a hidden layer with four neurons. The distance of drains computed via this method had a good agreement with real values and had a high precision in compare with other methods.