bluuebunny/crossref_metadata_2025_split huggingface dataset:
The orally active pterocarpanquinone LQB‐118 exhibits cytotoxicity in prostate cancer cell and tumor models through cellular redox stress
Authors: Martino Thiago , Kudrolli Tarana A. , Kumar Binod , Salviano Isis , Mencalha André , Coelho Marsen Garcia P. , Justo Graça , Costa Paulo R. Ribeiro , Sabino Kátia C. Carvalho , Lupold Shawn E. 
Published: November 2017

BackgroundThe targeted induction of reactive oxygen species (ROS) is a developing mechanism for cancer therapy. LQB‐118 is a pterocarpanquinone and ROS‐inducing agent with proven antineoplastic activity. Here, LQB‐118 efficacy and mechanism of activity, were examined in Prostate Cancer (PCa) cell and tumor models.MethodsPC3, LNCaP, and LAPC4 PCa cells were applied. Dicoumarol treatment was used to inhibit quinone reductase activity. N‐acetylcysteine (NAC) was applied as a ROS scavenger. ROS production was quantified by H2DCFDA flow cytometry. LQB‐118 treated cells were evaluated for changes in lipid peroxidation, viability, and apoptosis. Treatment‐induced gene expression was measured by RT‐qPCR and Western Blot. SOD1 knockdown was achieved with siRNA or miRNA mimic transfection. MicroRNA specificity was determined by 3′UTR reporter assay. Oral LQB‐118 treatment (10 mg/kg/day) efficacy was determined in athymic male nude mice bearing subcutaneous PC3 xenograft tumors.ResultsLQB‐118 treatment triggered PCa cell death and apoptosis. Therapeutic activity was at least partially dependent upon quinone reduction and ROS generation. LQB‐118 treatment caused an increase in cellular ROS and lipid peroxidation. Treated cells exhibited elevated levels of NQO1, Nrf2, and SOD1. The miRNAs miR‐206, miR‐1, and miR‐101 targeted and reduced SOD1 expression. The knockdown of SOD1, by siRNA or miRNA, enhanced LQB‐118 cytotoxicity. Orally administered LQB‐118 treatment significantly reduced the growth of established PCa xenograft tumors.ConclusionLQB‐118 is a developing and orally active pterocarpanquinone agent that effectively kills PCa cells through quinone reduction and ROS generation. The inhibition SOD1 expression enhances LQB‐118 activity, presumably by impairing the cellular antioxidant response.
Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic and intestinal in vitro cell models
Authors: Zhang Yuanyuan , LaCerte Carl , Kansra Sanjay , Jackson Jonathan P. , Brouwer Kenneth R. , Edwards Jeffrey E. 
Published: November 2017

AbstractObeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR‐mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich‐cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH. UDCA (≤100 μmol/L) alone did not inhibit CYP7A1 mRNA, and thus, no reduction in the endogenous bile acid pool observed. UDCA ≤100 μmol/L concomitantly administered with 0.1 μmol/L OCA had no effect on bile acid synthesis beyond what was observed with OCA alone. Furthermore, this study evaluated human Caco‐2 cells (clone C2BBe1) as in vitro intestinal models. Glycine conjugate of OCA increased mRNA levels of FXR target genes in Caco‐2 cells, FGF‐19, SHP, OSTα/β, and IBABP, but not ASBT, in a concentration‐dependent manner, while glycine conjugate of UDCA had no effect on the expression of these genes. The results suggested that UDCA ≤100 μmol/L did not activate FXR in human primary hepatocytes or intestinal cell line Caco‐2. Thus, co‐administration of UDCA with OCA did not affect OCA‐dependent pharmacological effects.
Examining the life course sequence of intending to move and moving
Authors: Clark William A.V. , Lisowski William 
Published: November 2017

AbstractThere is now a substantial body of research that examines the process of making decisions about moving. The questions of interest in that work and in this study using U.S. data are, first, how do life course changes get translated into intentions to move and, second, to what extent are intentions realised or unrealised. This study extends previous work by considering a longer interval in the planning process and by examining how life cycle changes create intentions, which in turn are translated, or not, into actual moves. We study the antecedents of the expressed intention to move and the outcomes that follow the expressed intention to move. We test the process of forming intentions and moving in the context of life course events and changes. We find that the subset of variables that create the intention to move vary subtly from the variables that create moves, though the triggering effects of family composition change are critical dimensions of both creating intentions and fulfilling those intentions by moving.
And then came Brexit: Experiences and future plans of young EU migrants in the London region
Authors: Lulle Aija , Moroşanu Laura , King Russell 
Published: November 2017

AbstractThis paper investigates the potential rupture that the United Kingdom's “Brexit” referendum of June 23, 2016, might bring about in intra‐European Union youth mobilities, with a specific focus on the London region. In many respects, and counter‐intuitively given the Brexit result, London has already become a “Eurocity”: a magnet for young people, both highly educated and less educated, from all over Europe who, especially since the turn of the millennium, have flocked to the city and its wider region to work, study, and play. Now, these erstwhile open‐ended migration trajectories have been potentially disrupted by a referendum result that few anticipated, and whose consequential results are still unclear. The main theoretical props for our analysis are the notions of “liquid migration,” “tactics of belonging,” “whiteness,” “privilege,” and “affect.” Data are drawn from 60 in‐depth interviews with Irish, Italian, and Romanian young‐adult students and higher and lower skilled workers, carried out in late 2015 and early 2016, plus 27 reinterviews carried out in late 2016, post‐Brexit. Results indicate participants' profound and generally negative reaction to Brexit and, as a consequence, a diversity of uncertainties and of plans over their future mobility: either to stay put using “tactics of belonging,” or to return home earlier than planned, or to move on to another country. Finally, we find evidence that new hierarchies and boundaries are drawn between intra‐European Union migrants as a result of Brexit.
Effectiveness of phase I applications for identifying randomly scattered out‐of‐control observations and estimating control chart parameters
Authors: Testik Murat Caner , Weiß Christian H. , Koca Yesim , Testik Ozlem Muge 
Published: November 2017

AbstractEstimation of unknown process parameters with fixed‐size samples are studied in the following. The standard textbook approach for phase I control chart implementation with a Shewhart control chart is evaluated for the case of normally distributed independent observations with random sampling. The
charts are simultaneously implemented by generating observations that have a given percentage of randomly scattered out‐of‐control observations. Simulating the phase I steps, where out‐of‐control samples are detected iteratively by determining trial control limits, identifying samples exceeding these limits, and revising the control limits, the standard practice is evaluated in terms of both detection performance and quality of parameter estimates. It is shown that standard phase I control chart implementations with 3‐σ‐limits may perform very poorly in identifying true out‐of‐control observations and providing a reference set of in‐control observations for estimation in some practical settings. A chart design with 2‐σ‐limits is recommended for a successful phase I analysis.
Bayesian design of life testing plans under hybrid censoring scheme
Authors: Bhattacharya Ritwik , Pradhan Biswabrata 
Published: November 2017

AbstractThis article describes Bayes design of hybrid‐censored life testing plans. A design criterion based on posterior variance of quantile of suitable order is proposed. The Weibull lifetime model with gamma prior distribution on model parameters is considered for illustration. Instead of using Markov chain Monte Carlo technique to compute the posterior quantities of interest, a large sample approximation is considered, which is easy to apply. Some life testing plans are presented. The effect of different prior information on the posterior quantity of interest is studied.
Improving negative liquid chromatography/electrospray ionization mass spectrometry lipidomic analysis of human plasma using acetic acid as a mobile‐phase additive
Authors: Monnin Cian , Ramrup Parsram , Daigle‐Young Carolann , Vuckovic Dajana 
Published: November 2017

RationaleMobile‐phase additives in liquid chromatography/mass spectrometry (LC/MS) are used to improve peak shape, analyte ionization efficiency and method coverage. Both basic and acidic mobile phases have been used successfully for negative electrospray ionization (ESI), but very few systematic investigations exist to date to justify the choice of mobile phase. Acetic acid was previously shown to improve ionization in untargeted metabolomics of urine, but has not been investigated in lipidomics. The goal of this study was to systematically compare the performance of acetic acid to that of other commonly employed additives in negative LC/ESI‐MS lipidomics.MethodsThe performance of acetic acid was compared to that of commonly used mobile‐phase additives in lipidomics, namely ammonium acetate, ammonium acetate with acetic acid and ammonium hydroxide, using lipid standard solutions containing representatives of major mammalian lipid subclasses and isopropanol‐precipitated human plasma. This design allowed comparison of the influence of additive and additive concentration on lipid signal intensity, lipid peak shape and lipid coverage in both simple and complex biological matrices using both Orbitrap and quadrupole time‐of‐flight MS platforms with different ESI source designs.ResultsAmmonium hydroxide caused 2‐ to 1000‐fold signal suppression of all lipid classes in comparison to acetic acid. In comparison to ammonium acetate, acetic acid increased lipid signal intensity from 2‐ to 19‐fold for 11 lipid subclasses, and decreased ionization efficiency only for ceramide and phosphatidylcholine lipid classes which can be effectively ionized in positive ESI mode. The improved ionization efficiency using acetic acid also increased lipid coverage by 21–50% versus ammonium acetate additive.ConclusionsAcetic acid at a concentration of 0.02% (v/v) is the suggested choice as a mobile‐phase additive for lipidomics and targeted lipid profiling with negative LC/ESI‐MS based on signal enhancement and improved lipid coverage compared to ammonium acetate, ammonium acetate with acetic acid and ammonium hydroxide mobile phases.
Investigation of metabolic profile of pimavanserin in rats by ultrahigh‐performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry
Authors: Wu Wenying , Chu Yanjie , Wang Shixiao , Sun Xiaoyang , Zhang Jingjing , Wang Yannian , Chen Xiaohui 
Published: November 2017

RationalePimavanserin, a selective serotonin 2A receptor inverse agonist, is a promising candidate for treating Parkinson's disease psychosis. Our previous study revealed that there might be the presence of extensive metabolites of pimavanserin in rats. However, the metabolic fate of pimavanserin in vivo remains unknown. Thus, it is essential to develop an efficient method to investigate the metabolic profile of pimavanserin in rats. Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR‐MS) to date has the highest mass measurement accuracy and resolution of any mass spectrometry platform.MethodsAfter a single intragastric administration of pimavanserin at a dose of 50 mg kg−1, plasma, bile, urine and feces were collected from rats. A novel and efficient strategy was developed to analyze the metabolic profile of pimavanserin in vivo based on ultrahigh‐performance liquid chromatography (UHPLC) coupled with FT‐ICR‐MS.ResultsA total of 23 metabolites were detected and tentatively identified through comparing their mass spectrometry profiles with those of pimavanserin. These metabolites were found in feces (22), bile (21), rat urine (16) and plasma (15). Results demonstrated that metabolic pathways of pimavanserin in rats included dehydrogenation, demethylation, deethylation, depropylation, debutylation, hydroxylation, dihydroxylation and trihydroxylation.ConclusionsA total of 22 phase I metabolites of pimavanserin were detected and tentatively identified. This report presents the first study of screening and identification of the metabolites of pimavanserin. The UHPLC/FT‐ICR‐MS method is a powerful tool for exploring and identifying metabolites in complex biological samples.
Pictures or pellets? Comparing camera trapping and dung counts as methods for estimating population densities of ungulates
Authors: Pfeffer Sabine E. , Spitzer Robert , Allen Andrew M. , Hofmeester Tim R. , Ericsson Göran , Widemo Fredrik , Singh Navinder J. , Cromsigt Joris P.G.M. 
Published: November 2017

AbstractAcross the northern hemisphere, land use changes and, possibly, warmer winters are leading to more abundant and diverse ungulate communities causing increased socioeconomic and ecological consequences. Reliable population estimates are crucial for sustainable management, but it is currently unclear which monitoring method is most suitable to track changes in multi‐species assemblages. We compared dung counts and camera trapping as two non‐invasive census methods to estimate population densities of moose Alces alces and roe deer Capreolus capreolus in Northern Sweden. For camera trapping, we tested the random encounter model (REM) which can estimate densities without the need to recognize individual animals. We evaluated different simplification options of the REM in terms of estimates of detection distance and angle (raw data vs. modelled) and of daily movement rate (camera trap based vs. telemetry based). In comparison to density estimates from camera traps, we found that, dung counts appeared to underestimate population density for roe deer, but not for moose. Estimates of detection distance and angle from modelled versus raw camera data resulted in nearly identical outcomes. The telemetry‐derived daily movement rate for moose and roe deer resulted in much higher density estimates than the camera trap‐derived estimates. We suggest that camera trapping may be a robust complement to dung counts when monitoring ungulate communities, particularly when similarities between dung pellets from sympatric deer species make unambiguous assignment difficult. Moreover, we show that a simplified use of the REM method holds great potential for large‐scale citizen science‐based programmes (e.g. involving hunters) that can track the rapidly changing European wildlife landscape. We suggest to include camera trapping in management programmes, where the analysis can be verified via web‐based applications.
Trag‐ und Verformungsverhalten von Verbundfugen mit elastischem Verbund
Authors: Kostadinova Natali , Kurz Wolfgang 
Published: November 2017

AbstractDie Leistungsfähigkeit moderner Verbundkonstruktionen aus Stahl und Beton wird maßgeblich durch das Trag‐ und Verformungsverhalten sowie das Verformungsvermögen der Verbundfuge mitbestimmt. Die weitere Entwicklung hinsichtlich der Sicherheit und Wirtschaftlichkeit verlangt ein tieferes Verständnis der Tragmechanismen, um auch die Verformungen und Verformbarkeiten der Tragelemente besser berücksichtigen zu können. Dabei haben die Verbundmittel und ihre Nachgiebigkeit eine enorme Rolle für das Trag‐ und Verformungsverhalten der Verbundkonstruktionen. Neben den Verschiebungen parallel zur Verbundfuge, die in den bestehenden Untersuchungen zur Theorie des verschieblichen Verbundes berücksichtigt werden, sollen auch die Abhebungen zwischen den Fügepartnern in die Untersuchungen eingehen. Das neuartige Berechnungsmodell von Verbundträgern wird zunächst auf die elastische Verformbarkeit von Kopfbolzendübeln aufgebaut. Das Bemessungsmodell mit seinen relevanten Parametern wird erläutert. Die Lösungsergebnisse werden mit Versuchsergebnissen und Simulationsberechnungen verglichen.
Zum Kleben stückverzinkter Bauteile
Authors: Abeln Björn , Richter Carl , Feldmann Markus 
Published: November 2017

AbstractEs soll ein Konzept für ein verlässliches klebtechnisches Fügen verzinkter Halbzeuge erarbeitet werden. Im Fokus stehen neben der Festigkeit der Zinkschicht selbst die Haftfestigkeit der Klebung auf der Zinkschicht stückverzinkter Bauteile sowie die sich daraus ergebende Definition geeigneter Oberflächenvorbehandlungsverfahren. Dazu werden drei höherfeste und hochmodulige Klebstoffe für die speziellen Anforderungen des Bauwesens ausgewählt. Als Oberflächenvorbehandlung kommen neben dem üblichen „Sweepen” zwei Beizmedien im Tauch‐ und Sprühverfahren zur Anwendung, womit ein selektiver Schichtabtrag im Bereich der Reinzinkphase der Zinkschicht eingestellt werden konnte. Die Untersuchung ungealterter und vorbewitterter Zinkschichten zeigt einen deutlichen Einfluss der Oberflächenvorbehandlung auf die Alterungsbeständigkeit der Klebverbunde. Die Ergebnisse von standardisierten Prüfkörpern können auf Kleinteilproben übertragen werden, mit deren Hilfe die Lastübertragung im Stahl‐Zinkschicht‐Klebstoff‐Verbund an praxisnahen Geometrien untersucht und die Beizanleitung im Herstellungsprozess auf ihre Anwendbarkeit bestätigt werden können. Mit den Untersuchungen konnte geklärt werden, wie Klebungen auf stückverzinkten Oberflächen konzeptioniert werden müssen, um gleiche Festig‐ und Zuverlässigkeiten wie auf unverzinkten Baustahloberflächen zu erhalten.
Querschnittsgestaltung von Stahlverbundbrücken
Authors: Wehnert‐Brigdar Alexandra , Sprinke Peter , Höfler Thomas 
Published: November 2017

AbstractHerrn Univ.‐Prof. Dr.‐Ing. Rolf Kindmann zur Vollendung seines 70. Lebensjahres gewidmetDas Verkehrsaufkommen insbesondere im Fernverkehrsnetz der Autobahnen hat sich in den letzten Jahrzehnten vervielfacht. Zur Engpassbeseitigung wird auf besonders beanspruchten Streckenabschnitten ein Ausbau der Verkehrsanlagen erforderlich. Der marode Brückenbestand wird in diesem Zusammenhang erneuert. Die Ausführung erfolgt in der Regel mit getrennten Richtungsfahrbahnen. Die zu erneuernden Teilbauwerke müssen dabei immer mehr Fahrstreifen mit Auswirkungen auf die Querschnittsgestaltung aufnehmen. In Abhängigkeit von Spannweiten und Überbaubreiten werden anhand von Beispielen mögliche Querschnittsformen bei Wahl eines Stahlverbundüberbaus vorgestellt. Die Vor‐ und Nachteile einzelner Querschnittsformen werden diskutiert.
Why does the orientation change mess up my Android application? From GUI failures to code faults
Authors: Amalfitano Domenico , Riccio Vincenzo , Paiva Ana C. R. , Fasolino Anna Rita 
Published: November 2017

SummaryThis paper investigates the failures exposed in mobile apps by the mobile‐specific event of changing the screen orientation. We focus on GUI failures resulting in unexpected GUI states that should be avoided to improve the apps quality and to ensure better user experience. We propose a classification framework that distinguishes 3 main classes of GUI failures due to orientation changes and exploit it in 2 studies that investigate the impact of such failures in Android apps. The studies involved both open‐source and apps from Google Play that were specifically tested exposing them to orientation change events. The results showed that more than 88% of these apps were affected by GUI failures, some classes of GUI failures were more common than others, and some GUI objects were more frequently involved. The app source code analysis allowed us to identify 6 classes of common faults causing specific GUI failures.
Factors Predicting Ethiopian Anesthetists’ Intention to Leave Their Job
Authors: Kols Adrienne , Kibwana Sharon , Molla Yohannes , Ayalew Firew , Teshome Mihereteab , van Roosmalen Jos , Stekelenburg Jelle 
Published: November 2017

AbstractBackgroundEthiopia has rapidly expanded training programs for associate clinician anesthetists in order to address shortages of anesthesia providers. However, retaining them in the public health sector has proven challenging. This study aimed to determine anesthetists’ intentions to leave their jobs and identify factors that predict turnover intentions.MethodsA nationally representative, cross‐sectional survey of 251 anesthetists working in public‐sector hospitals in Ethiopia was conducted in 2014. Respondents were asked whether they planned to leave the job in the next year and what factors they considered important when making decisions to quit. Bivariate and multivariable logistic regressions were conducted to investigate 16 potential predictors of turnover intentions, including personal and facility characteristics as well as decision‐making factors.ResultsAlmost half (n = 120; 47.8%) of anesthetists planned to leave their jobs in the next year, and turnover intentions peaked among those with 2–5 years of experience. Turnover intentions were not associated with the compulsory service obligation. Anesthetists rated salary and opportunities for professional development as the most important factors in decisions to quit. Five predictors of turnover intentions were significant in the multivariable model: younger age, working at a district rather than regional or referral hospital, the perceived importance of living conditions, opportunities for professional development, and conditions at the workplace.ConclusionsHuman resources strategies focused on improving living conditions for anesthetists and expanding professional development opportunities may increase retention. Special attention should be focused on younger anesthetists and those posted at district hospitals.