bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterologous Expression, Biosynthetic Studies, and Ecological Function of the Selective Gq‐Signaling Inhibitor FR900359
Authors: Crüsemann Max , Reher Raphael , Schamari Isabella , Brachmann Alexander O. , Ohbayashi Tsubasa , Kuschak Markus , Malfacini Davide , Seidinger Alexander , Pinto‐Carbó Marta , Richarz René , Reuter Tatjana , Kehraus Stefan , Hallab Asis , Attwood Misty , Schiöth Helgi B. , Mergaert Peter , Kikuchi Yoshitomo , Schäberle Till F. , Kostenis Evi , Wenzel Daniela , Müller Christa E. , Piel Jörn , Carlier Aurélien , Eberl Leo , König Gabriele M. 
Published: December 2017

AbstractThe cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia crenata, is a strong and selective inhibitor of Gq proteins, making it an indispensable pharmacological tool to study Gq‐related processes, as well as a promising drug candidate. Gq inhibition is a novel mode of action for defense chemicals and crucial for the ecological function of FR, as shown by in vivo experiments in mice, its affinity to insect Gq proteins, and insect toxicity studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic studies, and the novel analogue AC‐1, which demonstrates the flexibility of the FR starter condensation domains. Finally, expression of the frs genes in E. coli led to heterologous FR production in a cultivable, bacterial host for the first time.
A Six‐Oxidase Cascade for Tandem C−H Bond Activation Revealed by Reconstitution of Bicyclomycin Biosynthesis
Authors: Meng Song , Han Wei , Zhao Juan , Jian Xiao‐Hong , Pan Hai‐Xue , Tang Gong‐Li 
Published: December 2017

AbstractAs a commercial antibiotic, bicyclomycin (BCM) is currently the only known natural product targeting the transcription termination factor rho. It belongs to a family of highly functionalized diketopiperazine (DKP) alkaloids and bears a unique O‐bridged bicyclo[4.2.2]piperazinedione ring system, a C1 triol, and terminal exo‐methylene groups. We have identified and characterized the BCM biosynthetic pathway by heterologous biotransformations, in vitro biochemical assays, and one‐pot enzymatic synthesis. A tRNA‐dependent cyclodipeptide synthase guides the heterodimerization of leucine and isoleucine to afford the DKP precursor; subsequently, six redox enzymes, including five α‐ketoglutarate/Fe2+‐dependent dioxygenases and one cytochrome P450 monooxygenase, regio‐ and stereoselectively install four hydroxy groups (primary, secondary, and two tertiary), an exo‐methylene moiety, and a medium‐sized bridged ring through the functionalization of eight unactivated C−H bonds.
Kinetic studies of POSS–DGEBA precursors derived from monoamine functional POSS using dynamic dielectric sensing and nuclear magnetic resonance
Authors: Sharma Amit K. , Hassan Mohammad K. , Tu Jianwei , Mauritz Kenneth A. , Wiggins Jeffrey S. 
Published: December 2017

ABSTRACTIncorporation of pre‐reacted monofunctional polyhedral oligomeric silsesquioxane (POSS)–epoxy adducts dramatically improves dispersion of POSS in epoxy–amine networks. The relationship between reaction kinetics and mechanism for formation of POSS–epoxy adducts versus reaction temperature was investigated. Reactivities of epoxy–monoamine functional POSS molecules were determined using in situ reaction monitoring by dynamic dielectric sensing and 29Si NMR spectroscopy. The amine‐functional POSS–epoxy isothermal reaction showed reduced reactivity due to reduced molecular mobility, that is, diffusion limitations. Kinetic parameters were determined by fitting 29Si NMR data to the model of Kamal that was extended to include diffusion. Fitting of this model to experimental data showed very good agreement over the entire conversion range for pre‐reaction between amine‐functionalized POSS and epoxy. An autocatalytic mechanism, the same as that for the neat epoxy–amine systems, was indicated. Gel permeation chromatography, scanning electron microscopy and transmission electron microscopy were used to investigate molecular weight evolution and morphology of final networks cured by 4,4′ diaminodiphenyl sulfone using pre‐reacted POSS–epoxy adducts. POSS aggregate size decreased with increased pre‐reaction temperature; more homogenous POSS dispersion was observed with higher pre‐reaction temperature. Dynamic mechanical analysis demonstrated that Tg of composites decreased slightly compared to that of the neat matrix and there appeared to be little change in microstructural heterogeneity. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45994.
Association Between Marginal Jawbone Loss and Onset of Rheumatoid Arthritis and Relationship to Plasma Levels of RANKL
Authors: Kindstedt Elin , Johansson Linda , Palmqvist Py , Koskinen Holm Cecilia , Kokkonen Heidi , Johansson Ingegerd , Rantapää Dahlqvist Solbritt , Lundberg Pernilla 
Published: December 2017

ObjectiveTo investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.MethodsMarginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.ResultsBone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.ConclusionMarginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.
Temperaturwechselbeanspruchungen bei Fassaden: Konstruktionsweisen, Bewegungskonzepte und messtechnische Untersuchung
Authors: Junghanns Mike , Schmid Fabian 
Published: December 2017

AbstractIm Fassadenbau und insbesondere im Sonderfassadenbau sind verlässliche Auslegungswerkzeuge, der Muster‐ und Prototypenbau sowie umfangreiche Versuchsreihen unerlässlich, um die Produkte für einen regelkonformen und projektbezogenen Einsatz verlässlich entwickeln, planen und herstellen zu können. Wesentliche Anforderungen an Glas‐Stahl‐Konstruktionen und Element‐Fassaden sind die Dichtigkeit des gewählten oder entwickelten Konstruktionssystems sowie die Sicherheit der eingesetzten Produkte und Bauteile bei extremen Einflüssen. Die Konstruktionen müssen dabei eine Gebrauchstauglichkeit nach geltenden nationalen und lokalen Regelwerken sowie nach kundenseitig spezifizierten Einsatzszenarien erfüllen. Die Dichtigkeit und Gebrauchsfähigkeit der Konstruktionen ist dabei für den Regelbetrieb und für extreme Ereignisse, wie Temperaturwechselbeanspruchungen, Gebäudebewegungen oder Schadensereignissen, nachzuweisen und sicherzustellen. Bei Sonderkonstruktionen mit komplexer Geometrie sind an kritischen Konstruktionsdetails neben den üblichen Auslegungen auch Berechnungen, Simulationen sowie Tests und Versuche aus Ermangelung von übertragbaren Ergebnissen erforderlich. Dieser Aufsatz thematisiert deshalb Erfordernisse, Richtlinien und Prüfverfahren, die aus Temperaturwechselbeanspruchungen für Fassadenkonstruktionen resultieren. Aus Erfahrungen durch umfangreiche Versuche an Sonderkonstruktionen für den nordamerikanischen Markt werden kritische Randbedingungen bei Auslegung und Prüfung identifiziert, um abschließend Empfehlungen für die Weiterentwicklung und Anwendung der Risikoeinschätzung im Planungsprozess zu geben.
Group‐wise partial least square regression
Authors: Camacho José , Saccenti Edoardo 
Published: December 2017

AbstractThis paper introduces the group‐wise partial least squares (GPLS) regression. GPLS is a new sparse PLS technique where the sparsity structure is defined in terms of groups of correlated variables, similarly to what is done in the related group‐wise principal component analysis. These groups are found in correlation maps derived from the data to be analyzed. GPLS is especially useful for exploratory data analysis, because suitable values for its metaparameters can be inferred upon visualization of the correlation maps. Following this approach, we show GPLS solves an inherent problem of sparse PLS: its tendency to confound the data structure because of setting its metaparameters using standard approaches for optimizing prediction, like cross‐validation. Results are shown for both simulated and experimental data.
Application of near‐infrared spectroscopy combined with chemometrics for online monitoring of Moluodan extraction
Authors: Tao Lingyan , Li Wenjing , Jin Ye , Yang Yue , Wu Yongjiang , Liu Xuesong 
Published: December 2017

AbstractIn this study, the application of near‐infrared (NIR) spectroscopy for online monitoring of the Moluodan extraction process was investigated. Paeoniflorin, the main active component of Moluodan, was chosen as the quality index. Samples were partitioned into calibration and validation sets by random select and set partitioning based on joint X‐Y distances algorithm (SPXY), respectively. Wavelengths for modeling were selected by manual method and competitive adaptive reweighted sampling (Cars) algorithm. Particle swarm optimization–based least square support vector machines (PSO‐LS‐SVM) and partial least squares models were both established for quantitative analysis to determine the content of paeoniflorin online. At last, 8 models were obtained according to the combination of these algorithms and the SPXY‐Cars‐PSO‐LS‐SVM model had the best quantitative analysis performance compared with the other 7 models. Specifically, in the developed SPXY‐Cars‐PSO‐LS‐SVM model, the determination coefficients of the calibration
and validation
sets were 0.99 and 0.95, respectively, and the root mean square errors of the calibration and validation sets were 0.012 and 0.024 mg/mL, respectively, and the relative standard errors of the calibration and validation sets were 2.84% and 6.34%, respectively. These results suggested that the appropriate sample partition, wavelength selection, and regression analysis methods in this study, namely, the SPXY‐Cars‐PSO‐LS‐SVM algorithm combined with NIR spectroscopy, could be an effective and real‐time approach for online monitoring of the extraction process of Moluodan.
A Macroporous Metal–Organic Framework with Enhanced Hydrophobicity for Efficient Oil Adsorption
Authors: Jing Peng , Zhang Shi‐Yuan , Chen Wenjie , Wang Liang , Shi Wei , Cheng Peng 
Published: December 2017

AbstractThe applications of three‐dimensional superstructures that consist of metal–organic framework (MOF) crystals are promising, but limited by spatial control over the crystallization process. Here a hydrophobic hierarchical metal–organic framework (HZIF‐8) containing unusual micro‐, meso‐, and macropores was designed and synthesized by a template strategy, in which the polystyrene (PS) not only acted as the template to construct the macropores, but also modified the hydrophilic crystal surface of ZIF‐8. When used as adsorbent for liquid oil/water separation, HZIF‐8 demonstrated significantly enhanced oil adsorption performance while maintaining very low water uptake.
Methylsemicarbazide as a Ligand in Late 3d Transition Metal Complexes
Authors: Szimhardt Norbert , Stierstorfer Jörg 
Published: December 2017

AbstractMost ignition and initiation systems nowadays still contain poisonous chemicals such as lead styphnate and lead azide but also chromates and other compounds of high concern. Therefore, methylsemicarbazide (1, MSC), which can be prepared in a one‐step reaction and in an extraordinary high yield of 95 %, has been evaluated as ligand in energetic coordination compounds. For the first time 25 new transition metal complexes (Mn2+, Ni2+, Co2+, Cu2+, and Zn2+) using methylsemicarbazide (1) as the ligand were prepared and comprehensively analyzed by, for example, XRD, IR, EA, UV/Vis and DSC/DTA/TGA. Many show a strong energetic character, which can be tuned by using different anions such as Cl−, SO42−, NO3−, ClO4−, picrate or styphnate. Selected compounds were additionally evaluated as lead‐free primary explosives in initiation tests (nitropenta filled detonators) and in laser ignition systems. Especially compound 7 showed very promising results during these tests and could be a potential candidate for future applications.
Lipid‐DNAs as Solubilizers of mTHPC
Authors: Liu Yun , de Vries Jan Willem , Liu Qing , Hartman Alwin M. , Wieland Gerhard D. , Wieczorek Sebastian , Börner Hans G. , Wiehe Arno , Buhler Eric , Stuart Marc C. A. , Browne Wesley R. , Herrmann Andreas , Hirsch Anna K. H. 
Published: December 2017

AbstractHydrophobic drug candidates require innovative formulation agents. We designed and synthesized lipid‐DNA polymers containing varying numbers of hydrophobic alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by introducing a defined number of alkyl chain‐modified nucleotides during standard solid‐phase synthesis of DNA using an automated DNA synthesizer. We observed that the resulting self‐assembled micelles solubilize the poorly water‐soluble drug, meta‐tetra‐hydroxyphenyl‐chlorin (mTHPC) used in photodynamic therapy (PDT) with high loading concentrations and loading capacities. A cell viability study showed that mTHPC‐loaded micelles exhibit good biocompatibility without irradiation, and high PDT efficacy upon irradiation. Lipid‐DNAs provide a novel class of drug‐delivery vehicle, and hybridization of DNA offers a potentially facile route for further functionalization of the drug‐delivery system with, for instance, targeting or imaging moieties.
Green Photo‐Organocatalytic C−H Activation of Aldehydes: Selective Hydroacylation of Electron‐Deficient Alkenes
Authors: Papadopoulos Giorgos N. , Voutyritsa Errika , Kaplaneris Nikolaos , Kokotos Christoforos G. 
Published: December 2017

AbstractSelective C−H activation is an area of growing importance. Metal‐free C−H activation of branched aldehydes mediating the hydroacylation of electron‐deficient alkenes is an attractive transformation, but is limited by selectivity issues, especially in the case of α,α‐disubstituted aldehydes. Herein, we report a green, cheap, versatile, and easily reproducible selective hydroacylation of alkenes utilizing phenylglyoxylic acid as the photocatalyst and common household bulbs for irradiation, leading to products in excellent yields and selectivities. The reaction mechanism was also studied to account for the high selectivity.
Preservative effects of some selected spice oleoresins to stabilize the sunflower oil in comparison to tertiary butylhydroquinone
Authors: Pradhananga Mahalaxmi , Manandhar Pratibha 
Published: December 2017

AbstractDPPH (1, 1‐Diphenyl‐2‐Picrylhydrazyl) radical scavenging activity was performed to find out the antioxidant activity (AA) of all the antioxidants used at a concentration of 5, 10, and 15 μl/ml. Effect of spice oleoresins (clove, black pepper, and ginger) (200 ppm) and TBHQ (200 ppm) were incorporated in stabilizing refined, bleached, and deodorized (RBD) sunflower oil heating at frying temperature (170°C) and during accelerated oxidation storage (70°C) was studied in comparison to Tert‐Butylhydroquinone (TBHQ). Antioxidant activity (AA) was found to be in the order TBHQ > clove > ginger > pepper at a concentration of 5; 10; 15 μl/ml. A direct correlation was found between AA and the effectiveness of oleoresins and TBHQ in controlling AV and PV of the sunflower oil. During both heating and storage, TBHQ was found most effective to control AV and PV followed by clove, pepper, and ginger.
Task Force Drainage (TFD) – The project for life after
Authors: Schachinger Tobias , Sperger Lukas , Heissenberger Roman , Wagner Oliver Kai 
Published: December 2017

AbstractThe ÖBB‐Infrastruktur AG currently has several very large tunnelling projects in Austria. However, not only the construction itself is important for the client, but also that the tunnels can be used as efficiently as possible during their entire service life. Regarding water pressure‐relieved tunnel structures, the drainage system is usually the most expensive and time‐consuming maintenance activity. For this reason a specialized project, the Task Force Drainage (TFD), was launched to deal with drainage systems during construction and operation. The objectives of the TFD are primarily the concentration of innovation regarding the drainage system, the optimization and systematization of the maintenance process and the specification of necessary components and technologies. Examples are the development of new flushing systems for the drainage system, the development of optimized pipe materials and a uniform inventory of existing drainage systems. These examples are explained in the article.
Cameras for digitized 3D geological documentation of the tunnel face from cutterheads of TBMs
Authors: Wenighofer Robert , Six Gerhard , Galler Robert , Chmelina Klaus 
Published: December 2017

AbstractA camera system has been developed, which can cover the full face when mounted in disc housings, thus imaging the tunnel face to provide greater transparency for client and contractor and to provide more objective geological assessment. No manholes or extra apertures are needed to accommodate the camera system. The images recorded are used to generate a 3D reconstruction of the face, revealing depths and volumes of breakouts. For the determination of the orientation of discontinuities, plugins based on .NET have been developed to enable the use of AutoCAD or Civil3d of Autodesk for the geological assessment of the face. The contribution describes the application, images and computed results of the camera system based on its regular use over a period of more than 20 months.
The railway station Mürzzuschlag in relation to the Semmering Base Tunnel
Authors: Gobiet Gerhard 
Published: December 2017

AbstractThe opening of the Semmering Base Tunnel (SBT from timetable change in 2026/27) will change the characteristics of the Baltic‐Adriatic axis from a mountain railway to a flat trajectory. This will revalue the trans‐European route in the Austrian segment with lasting effect. In future, the railway station at Mürzzuschlag will play an even more important role in the Baltic‐Adriatic axis than today. The connection to the metropolitan area of Vienna will bring a time saving for long‐distance passenger traffic of about 30 minutes. The rail freight traffic will profit from the fact that train will no longer run over the mountains. The enlargement of the park & ride facility, the improved connection to public transport as part of the transformation of the forecourt, the enlargement of the ASC location and the adaptation of the existing station buildings will improve Mürzzuschlag station with lasting effect.
Development of holistic prognosis models using exploration techniques and seismic prediction
Authors: Reinhold Chris , Schwarz Christian , Bergmeister Konrad 
Published: December 2017

AbstractAs part of the Brenner Base Tunnel project, the currently running Tulfes‐Pfons construction lot includes a stretch of the exploratory tunnel (ET), which has a length of 15 km and is being bored by a gripper TBM. During this tunnelling work, a diverse and broad set of exploration techniques is being used. Although it is an exploratory tunnel, the tunnel is subject to the same constraints as a performance heading. The choice of exploration techniques was made with regard of the capability to smoothly integrate them into regular tunnelling in order to not create further downtime. The exploration techniques are useful for the current ET but also to produce a forecast for the subsequent main tunnels (MT). The geological investigation is undertaken by face and peripheral mapping as well as by percussion drilling ahead of the machine. The geotechnical exploration is carried out by analysing the TBM parameters and the system behaviour, and analysing the percussion drilling. The exploration concept is completed with the geophysical reflection seismic method. All these exploration methods have different sensitivities, exploration ranges and directions, strengths and weaknesses, so they complement one another. This paper assesses the exploration techniques based on the experience until now. A case study of one fault zone is presented to show how the different exploration methods interact and contribute to a holistic prognosis model.
Contemplating Resectability
Authors: Shuman Andrew G. 
Published: December 2017

AbstractSuzie loves to talk. A successful mid‐thirties businesswoman, she is a self‐described social butterfly—which made her diagnosis of tongue cancer even more devastating. She came to the clinic complaining of a lump in her throat, which in most young healthy people turns out to be benign and easily treated. But not for Suzie, who had a very rare salivary tumor arising in the back of her tongue. Its slow growth was both a blessing and a curse; such tumors do not kill people quickly, but they typically require surgery. It would slowly and relentlessly grow until and unless we removed most of her tongue. In head and neck surgery, issues of appearance, identity, function, and communication are the foremost considerations when we decide when, and whether, to operate. As the adage goes, knowing when not to operate is the sine qua non of the wise surgeon. But the inverse is also true.
The Real‐World Ethics of Adaptive‐Design Clinical Trials
Authors: Bothwell Laura E. , Kesselheim Aaron S. 
Published: December 2017

AbstractFrom the earliest application of modern randomized controlled trials in medical research, scientists and observers have deliberated the ethics of randomly allocating study participants to trial control arms. Adaptive RCT designs have been promoted as ethically advantageous over conventional RCTs because they reduce the allocation of subjects to what appear to be inferior treatments. Critical assessment of this claim is important, as adaptive designs are changing medical research, with the potential to significantly shift how clinical trials are conducted. Policy‐makers are swiftly moving to encourage greater use of adaptive designs. In 2016, the newly enacted 21st Century Cures Act instructed the Food and Drug Administration to help product sponsors incorporate adaptive methods into proposed clinical trial protocols and applications for investigational drugs and also biological products. In this article, we review the ethical justifications commonly offered for adaptive designs, explore these arguments in the context of actual trials, and contend that clinical equipoise is a useful standard for adaptive‐trial ethics. We distinguish between theoretical and clinical equipoise and explain why ethical arguments related to adaptive trials tend to focus on the former. Yet we contend that theoretical equipoise can be an unreliable standard for adaptive ethics. While we contend that clinical equipoise is the most critical principle for the primary ethical concerns posed by adaptive trials, we suggest ethical approaches to deal with some additional concerns unique to adaptive designs.