bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid
Authors: Wilkinson Isabel V. L. , Perkins Kelly J. , Dugdale Hannah , Moir Lee , Vuorinen Aini , Chatzopoulou Maria , Squire Sarah E. , Monecke Sebastian , Lomow Alexander , Geese Marcus , Charles Philip D. , Burch Peter , Tinsley Jonathan M. , Wynne Graham M. , Davies Stephen G. , Wilson Francis X. , Rastinejad Fraydoon , Mohammed Shabaz , Davies Kay E. , Russell Angela J.
Published: November 2019

Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies.
3D HydroMapper – digitale Inspektion von Bauwerken über und unter Wasser
Authors: Holste Karsten , Hesse Christian , Neumann Ingo , Bassen Sebastian
Published: November 2019

Die Alterung der Infrastruktur im Bereich der Wasserstraßen führt in Verbindung mit den in Norddeutschland häufig schwierigen Sichtverhältnissen unter Wasser zu massiven Aufwendungen der Betreiber bei der Inspektion, der Bewertung und der Instandsetzung der Verkehrswasserbauwerke. Das vom BMVI mit Forschungsmitteln geförderte und im Dezember 2018 gestartete Projekt 3D HydroMapper soll die Erfassung und Nutzung der 3‐D‐Scandaten von Bestandsbauwerken über und unter Wasser verbessern. Hierzu sollen neuartige Positionierungs‐ und Routingverfahren sowie eine aktive Objektausrichtung der Sensorik genutzt werden, um den Zustand von Bauwerken mit sehr hoher Präzision und Auflösung im Bereich weniger Zentimeter auch unter Wasser strukturiert zu erfassen. Erste Testergebnisse zeigen, dass mit dem 3D HydroMapper ein echter Innovationssprung möglich ist.
Comprehensive investigation of succinic acid production by Actinobacillus succinogenes: a promising native succinic acid producer
Authors: Yang Qiao , Wu Min , Dai Zhongxue , Xin Fengxue , Zhou Jie , Dong Weiliang , Ma Jiangfeng , Jiang Min , Zhang Wenming
Published: November 2019

The biological production of succinic acid has attracted a great deal of attention due to the depletion of fossil fuels and concerns regarding environmental issues. As a natural producer of succinic acid, Actinobacillus succinogenes is one of the most promising candidates owning to its high production capability, wide carbon utilization spectrum, and robustness to environmental factors. This review details current achievements attempting to improve the efficiency of succinic acid production, not only in terms of raw materials and metabolic engineering strategies but also in terms of process optimization, such as work on neutralizing agents, redox potential, and the supply of CO2. Strategies to reduce the accumulation of byproduct accumulation and to improve succinic acid synthesis are discussed. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Quantitative assessment of adverse events in clinical trials: Comparison of methods at an interim and the final analysis
Authors: Hollaender Norbert , Gonzalez‐Maffe Juan , Jehl Valentine
Published: November 2019

In clinical study reports (CSRs), adverse events (AEs) are commonly summarized using the incidence proportion (IP). IPs can be calculated for all types of AEs and are often interpreted as the probability that a treated patient experiences specific AEs. Exposure time can be taken into account with time‐to‐event methods. Using one minus Kaplan–Meier (1‐KM) is known to overestimate the AE probability in the presence of competing events (CEs). The use of a nonparametric estimator of the cumulative incidence function (CIF) has therefore been advocated as more appropriate. In this paper, we compare different methods to estimate the probability of one selected AE. In particular, we investigate whether the proposed methods provide a reasonable estimate of the AE probability at an interim analysis (IA). The characteristics of the methods in the presence of a CE are illustrated using data from a breast cancer study and we quantify the potential bias in a simulation study. At the final analysis performed for the CSR, 1‐KM systematically overestimates and in most cases IP slightly underestimates the given AE probability. CIF has the lowest bias in most simulation scenarios. All methods might lead to biased estimates at the IA except for AEs with early onset. The magnitude of the bias varies with the time‐to‐AE and/or CE occurrence, the selection of event‐specific hazards and the amount of censoring. In general, reporting AE probabilities for prespecified fixed time points is recommended.
The role of Interleukin 1 receptor antagonist in mesenchymal stem cell‐based tissue repair and regeneration
Authors: Harrell Carl Randall , Markovic Bojana Simovic , Fellabaum Crissy , Arsenijevic Nebojsa , Djonov Valentin , Volarevic Vladislav
Published: November 2019

Interleukin (IL)‐1 receptor antagonist (IL‐1Ra), a naturally occurring antagonist of IL‐1α/IL‐1β signaling pathways, has been attributed to the immunosuppressive effects of mesenchymal stem cells (MSCs). MSCs, in IL‐1Ra‐dependent manner, suppressed production of IL‐1β in dermal macrophages, induced their polarization in anti‐inflammatory M2 phenotype, attenuated antigen‐presenting properties of dendritic cells (DCs), and promoted expansion of immunosuppressive T regulatory cells in the skin, which resulted in enhanced repair of the nonhealing wounds. Reduced activation of inflammasome and suppressed production of IL‐1β in macrophages were mainly responsible for beneficial effects of MSC‐derived IL‐1Ra in alleviation of acute lung injury, dry eye syndrome, and corneal injury. Through the production of IL‐1Ra, MSCs reduced migration of DCs to the draining lymph nodes and attenuated generation of inflammatory Th1 and Th17 cells that resulted in alleviation of fulminant hepatitis and rheumatoid arthritis. MSCs, in IL‐1Ra‐dependent manner, reduced liver fibrosis by suppressing production of Type I collagen in hepatic stellate cells. IL‐1Ra was, at least partially, responsible for enhanced proliferation of hepatocytes and chondrocytes in MSC‐treated animals with partial hepatectomy and osteoarthritis. Despite of these beneficial effects, IL‐1Ra‐dependent inhibition of IL‐1α/IL‐1β‐signaling significantly increased risk of infections. Therefore, future experimental and clinical studies should delineate potential side effects of MSC‐derived IL‐1Ra before IL‐1Ra‐overexpressing MSCs could be used as a potentially new therapeutic agent for the treatment of acute and chronic inflammatory diseases.
In vivo quantification and pharmacokinetic studies of cotinine in mice after smoke exposure by LC–MS/MS
Authors: El Mubarak Mohamed A. , Danika Charikleia , Cachon Charlyne , Korovila Charalambia , Atsopardi Korina , Panagopoulos Nikolaos , Margarity Marigoula , Poulas Konstantinos , Sivolapenko Gregory B.
Published: November 2019

A sensitive analytical method was developed and validated for the quantification of cotinine in mouse plasma after exposure to smoke of 0.5, 1.0, and 1.5 commercially available cigarettes, using liquid chromatography tandem mass spectrometry. The method was validated over a linear concentration range of 0.075–20.0 ng/mL with the R2 value being higher than 0.99. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. The lower limit of quantification (LLOQ) for cotinine was 0.075 ng/mL with sufficient specificity, accuracy, and precision. Following exposure to 0.5, 1.0, and 1.5 cigarette smoke, it was observed that the AUC and the Cmax increased linearly as the doses increased. The pharmacokinetics of cotinine was found linear for the range of 0.5–1.5 commercial cigarette smoke. The quantification of the concentration of cotinine in mouse plasma after smoke exposure will facilitate future behavioral and toxicological experiments in animals and may prove useful in predicting cotinine levels in humans during smoking.
Mammalian cell cultivation using nutrients extracted from microalgae
Authors: Okamoto Yuta , Haraguchi Yuji , Sawamura Naoya , Asahi Toru , Shimizu Tatsuya
Published: November 2019

Mammalian cells have been used in various research fields. More recently, cultured cells have been used as the cell source of “cultured meat.” Cell cultivation requires media containing nutrients, of which glucose and amino acids are the essential ones. These nutrients are generally derived from grains or heterotrophic microorganisms, which also require various nutrients derived from grains. Grain culture, in turn, requires many chemical fertilizers and agrochemicals, which can cause greenhouse gas emission and environmental contamination. Furthermore, grain production is greatly influenced by environmental changes. In contrast, microalgae efficiently synthesize various nutrients using solar energy, water, and inorganic substances, which are widely used in the energy sector. In this study, we aimed to apply nutrients extracted from microalgae in the culture media for mammalian cell cultivation. Glucose was efficiently extracted from Chlorococcum littorale or Arthrospira platensis using sulfuric acid, whereas 18 of the 20 proteinogenic amino acids were efficiently extracted from Chlorella vulgaris using hydrochloric acid. We further investigated whether nutrients present in the algal extracts could be used in mammalian cell cultivation. Although almost all C2C12 mouse myoblasts died during cultivation in a glucose‐ and amino acid‐free medium, the cell death was rescued by adding algal extract(s) into the nutrient‐deficient media. This indicates that nutrients present in algal extracts can be used for mammalian cell cultivation. This study is the first step toward the establishment of a new cell culture system that can reduce environmental loads and remain unaffected by the impact of environmental changes.
Leadership expert shares practical strategies for making shifts that lead to success
Authors: McCarthy Claudine
Published: November 2019

ORLANDO, FLA. — Yesterday's style of leadership is no longer enough to effectively lead your organization today.
The Two Classic Pb2+‐Selective DNAzymes Are Related: Rational Evolution for Understanding Metal Selectivity
Authors: Ren Wei , Huang Po‐Jung Jimmy , He Meilin , Lyu Mingsheng , Wang Shujun , Wang Changhai , Liu Juewen
Published: November 2019

In 1994, the first DNAzyme named GR5 was reported, which specifically requires Pb2+ for its RNA cleavage activity. Three years later, the 8‐17 DNAzyme was isolated. The 8‐17 DNAzyme and the related 17E DNAzyme are also most active with Pb2+, although other divalent metals can work as well. GR5 and 17E have the same substrate sequence, and their catalytic loops in the enzyme strands also have a few similar and conserved nucleotides. Considering these, we hypothesized that 17E might be a special form of GR5. To test this hypothesis, we performed systematic rational evolution experiments to gradually mutate GR5 toward 17E. By using the activity ratio in the presence of Pb2+ and Mg2+ for defining these two DNAzymes, the critical nucleotide was identified to be T12 in 17E for metal specificity. In addition, G9 in GR5 is a position not found in most 17E or 8‐17 DNAzymes, and G9 needs to be added to rescue GR5 activity if T12 becomes a cytosine. This study highlights the links between these two classic and widely used DNAzymes, and offers new insight into the sequence–activity relationship related to metal selectivity.
Transition‐Metal‐Free Reverse Reactivity of (2‐Alkynyl)‐Arylaldimines: Assembly of Functionalized Amino‐Indinones
Authors: Saini Kapil Mohan , Saunthwal Rakesh K. , Sushmita  , Verma Akhilesh K.
Published: November 2019

Transition‐metal‐free regioselective synthesis of functionalized amino‐indenones by the reaction of ortho‐alkynylaldehydes with a broad range of primary amines by intramolecular cyclization has been described. The designed reaction proceeds through KOH‐mediated Prins‐type cyclization and DMSO‐promoted oxidation of the cyclopent‐2‐en‐1‐one system. The proposed mechanism and role of solvent were well supported by control experiments. For the first time, we have disclosed the reverse reactivity of (2‐alkynyl)‐arylaldimines in a super basic system.
Barium‐Catalysed Dehydrocoupling of Hydrosilanes and Borinic Acids: A Mechanistic Insight
Authors: Le Coz Erwann , Zhang Ziyun , Roisnel Thierry , Cavallo Luigi , Falivene Laura , Carpentier Jean‐François , Sarazin Yann
Published: November 2019

Two very rare cases of barium boryloxides, the homoleptic [Ba(OB{CH(SiMe3)2}2)2⋅C7H8] and the heteroleptic [{LONO4}BaOB{CH(SiMe3)2}2] stabilised by the multidentate aminoetherphenolate {LONO4}−, are presented, and their structural properties are discussed. The electron‐deficient [Ba(OB{CH(SiMe3)2}2)2⋅C7H8] shows, in particular, resilient η6‐coordination of the toluene molecule. Together with its amido parents [Ba{N(SiMe3)2}2⋅thf2] and [Ba{N(SiMe3)2}2]2, this complex catalyses the fast and chemoselective dehydrocoupling of borinic acids R2BOH and hydrosilanes HSiR′3, yielding borasiloxanes R2BOSiR′3 in a controlled fashion. The assessment of substrate scope indicates that, for now, the reaction is limited to bulky borinic acids. Kinetic analysis shows that the rate‐limiting step of the catalytic manifold traverses a dinuclear transition state. A detailed mechanistic scenario is proposed on the basis of DFT computations, the results of which are fully consistent with experimental data. It consists of a stepwise process with rate‐determining nucleophilic attack of a metal‐bound O‐atom onto the incoming hydrosilane, involving throughout dinuclear catalytically active species.
Effect of enantiomerism on the bioequivalence of a new ibuprofen 600‐mg tablet formulation obtained by roller compaction
Authors: Matji Antonio , Vargas Emilio , Carvajal Luis , Terleira Ana Isabel , Portolés Antonio , Garcia‐Arieta Alfredo , Torrado Juan J. , Serrano Dolores R.
Published: November 2019

The bioequivalence of a new ibuprofen 600‐mg film‐coated tablet obtained by roller compaction was studied in a crossover study with 22 healthy volunteers. Bioequivalence was analyzed based on (a) the S‐enantiomer, (b) the R‐enantiomer, and (c) the sum of both enantiomers (representing the results of an achiral assay). The bioequivalence conclusion for ibuprofen products should be based not only on AUC and Cmax but also on tmax since tmax is related to the onset of action. However, it is not possible to ensure if bioequivalence has been demonstrated for tmax as regulators have not defined the acceptance range for the difference between medians of tmax in those cases, where tmax is clinically relevant. In this study, it was possible to conclude bioequivalence for tmax based on S‐ibuprofen, though this conclusion might be questioned if the decision is based on R‐ibuprofen or the achiral method.
Lithium‐air battery
Authors: Rosenberg Dominique , Jansen Walter
Published: November 2019

Batterien auf Lithium‐Ionen‐Basis sind in der heutigen Zeit die meistverwendeten Energiespeicher für Elektronikgeräte wie Tablets, Smartphones und Co. Auch in der Automobilbranche im Bereich der Elektro‐ und Hybridfahrzeuge sowie bei der Energiewende gelten sie als Hoffnungsträger zur Energiespeicherung. Dabei wird vor allem an verschiedenen Elektrolyten und Elektrodenmaterialien der Lithium‐Ionen‐Technologie geforscht. Eine leistungsstärkere Alternative könnte die Lithium‐Sauerstoff‐Batterie sein. Diese lässt sich mit verschiedenen Versuchsaufbauten für den Chemieunterricht und dem Hochschulpraktikum gut darstellen und leicht experimentell untersuchen.
Novel Pyrimidines as Multitarget Protein Tyrosine Kinase Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)
Authors: Sun Bo , Liu Xiaowen , Zheng Xu , Wang Changyuan , Meng Qiang , Sun Huijun , Shu Xiaohong , Liu Kexin , Sun Xiuli , Li Yanxia , Ma Xiaodong
Published: November 2019

A new class of pyrimidine derivatives were identified as potent protein tyrosine kinase (PTK) inhibitors for the treatment of idiopathic pulmonary fibrosis (IPF). Most of these small‐molecule inhibitors displayed strong enzymatic activity against BTK and JAK3 kinases at concentrations lower than 10 nM. The representative compound N‐(3‐((5‐chloro‐2‐(4‐((1‐morpholino)acetylamino)phenylamino)‐4‐pyrimidinyl)amino)phenyl)acrylamide (6 a) also exhibited high inhibitory potency toward both BTK and JAK kinase families, as well as ErbB4, at a concentration of 10 nM, achieving rates of inhibition higher than 57 %. Additionally, in vivo biological evaluations showed that 6 a can remarkably decrease the severity of IPF disease. All these investigations suggested that the multi‐PTK inhibitor 6 a may serve as a promising agent for the treatment of IPF.
Evolutionary shifts dramatically reorganized the human hippocampal complex
Authors: Schilder Brian M. , Petry Heywood M. , Hof Patrick R.
Published: November 2019

The hippocampal complex (HC) is central to long‐term memory storage and retrieval as well as spatial navigation across many species. Notably, humans appear to have greatly enhanced and possibly unique HC‐mediated capacities such as constructive episodic simulation. Key studies have shown that the human HC is disproportionately large amongst hominoids, but much remains unknown at the levels of substructural evolutionary reorganization and ecological selection. Here, we calculated relative sizes of 12 HC subregions in a diverse sample of 44 primate species. We then used a Bayesian phylogenetic method, selective regime analysis, to identify 27 separate evolutionary shifts in HC organization across 65 million years of primate evolution. Additionally, a series of multivariate phylogenetic regressions using HC‐related ecological variables as predictors (Diet Breadth, Population Density, Group Size, Home Range Size, and Residual Home Range) revealed that relative fascia dentata and CA1 size were both significantly predicted by species' home range size (after correcting for body size). However, perhaps the most notable finding of this study was that the shifts in HC size and subregional organization in the human lineage were the largest seen in all of primate evolution, rendering modern humans with a HC that is a clear outlier amongst all nonhuman primates investigated here. Given the extensive literature confirming the relationship between HC organization and function, these selective shifts are likely to have played a significant role in the emergence of human‐specific capacities, such as constructive episodic simulation.
Boolean Logic Networks Mimicked with Chimeric Enzymes Activated/Inhibited by Several Input Signals
Authors: Bollella Paolo , Bellare Madhura , Kadambar Vasantha Krishna , Guo Zhong , Alexandrov Kirill , Melman Artem , Katz Evgeny
Published: November 2019

Reactions catalyzed by artificial allosteric enzymes, chimeric proteins with fused biorecognition and catalytic units, were used to mimic multi‐input Boolean logic systems. The catalytic parts of the systems were represented by pyrroloquinoline quinone‐dependent glucose dehydrogenase (PQQ‐GDH). Two biorecognition units, calmodulin or artificial peptide‐clamp, were integrated into PQQ‐GDH and locked it in the OFF or ON state respectively. The ligand‐peptide binding cooperatively with Ca2+ cations to a calmodulin bioreceptor resulted in the enzyme activation, while another ligand‐peptide bound to a clamp‐receptor inhibited the enzyme. The enzyme activation and inhibition originated from peptide‐induced allosteric transitions in the receptor units that propagated to the catalytic domain. While most of enzymes used to mimic Boolean logic gates operate with two inputs (substrate and co‐substrate), the used chimeric enzymes were controlled by four inputs (glucose – substrate, dichlorophenolindophenol – electron acceptor/co‐substrate, Ca2+ cations and a peptide – activating/inhibiting signals). The biocatalytic reactions controlled by four input signals were considered as logic networks composed of several concatenated logic gates. The developed approach allows potentially programming complex logic networks operating with various biomolecular inputs representing potential utility for different biomedical applications.
Luminescent and Chiroptical Properties of 1 : 1 Eu (III) : Tetracycline Species Probed by Circularly Polarized Luminescence
Authors: Deol Kirandeep K. , Muller Gilles
Published: November 2019

This study investigates the significantly different luminescent and chiroptical properties of tetracycline (TC) when coordinated to Eu(III). The approach involves understanding the 1) speciation of TC and 2) conformation and species formed between Eu(III) and TC in a ratio of 1 : 1 in a dimethylformamide (DMF) solution and as a function of the pH value. By identifying the conformational changes of the various 1 : 1 Eu(III) : TC species, the results from this study explain information on the local microenvironment about the Eu(III) metal center. In particular, 5D0←7F0 Eu(III) laser excitation spectroscopy was employed to distinguish the different types of species found in solution in order to understand the interaction between Eu(III) and TC. On the other hand, circularly polarized luminescence (CPL) spectroscopy was used to understand the structural changes within the 1 : 1 Eu(III) : TC complex that could be related to the chirality of the Eu(III)‐containing species. The CPL spectrum serves as a “fingerprint” to indicate the conformational changes within the 1 : 1 Eu(III) : TC complex as a result of the chiroptical signal arising from the various Eu(III) : TC species.
Consider these three models of faculty leadership development
Authors: Pavlik Amelia
Published: November 2019

Experts. It's a word you'd likely use to describe your faculty members when it comes to their research focus. But would you feel comfortable using the same term to describe their leadership skills?
Learn leadership lessons from the unwavering
Authors: Hodges Dawn Z.
Published: November 2019

Over my 38‐year career in higher education I worked, directly or indirectly, for 12 college presidents. Some were good, some mediocre, and one was horrific. But only one was nearly perfect. Of course, he wouldn't think so. He was a humble man.
Leadership positions create opportunities to serve your campus, student body
Authors: Sutton Halley
Published: November 2019

“Like most [higher education] administrators, I never thought I'd become an administrator. It's often seen as evil, like you either can't teach or can't publish,” said Amy Sueyoshi, Dean of the College of Ethnic Studies at San Francisco State University. In fact, when she was first offered the position as an administrator (moving from her former role in academia at SFSU), Sueyoshi was hospitalized for chest pains, and stayed at Kaiser overnight for monitoring, with fears that she was suffering from a heart condition. As it turned out, Sueyoshi was suffering from a panic attack. “That's how striking the position was,” she said. But when the position was reframed to her as a position of service, Sueyoshi made her decision. “I'm all about service,” Sueyoshi said.
Associations between maternal depression and mother and infant oxytocin receptor gene (OXTR_rs53576) polymorphisms
Authors: Asherin Ryan M. , Everhart Kevin D. , Stophaeros Sunny L. , Vogeli Jo M. , Fowler Joshua , Phiel Christopher J. , Kaplan Peter S.
Published: November 2019

Polymorphisms in the oxytocin receptor gene, OXTR_rs53576, have been linked to differences in maternal sensitivity and depressive symptoms. Although some studies suggest the A allele confers risk for mood disorders, individuals homozygous for the G allele may exhibit greater sensitivity to both positive and negative social experiences, including in the mother–infant dyad. Given the bi‐directional nature of mother–infant influences on maternal mood, we tested the association between both mothers’ and infants’ OXTR_rs53576 genotype and maternal depression, as assessed through a self‐report inventory. Although Beck Depression Inventory (BDI‐II) scores were significantly higher for GG in comparison to AG/AA mothers, and for mothers of GG in comparison to AG/AA infants, an ANCOVA revealed that after sociodemographic risk factors had been controlled, infants’, but not mothers’, OXTR genotype predicted maternal depression scores, with no significant interaction between the two. The effect of infant OXTR on maternal depression was not explained by maternal reports of difficult infant temperament. We propose that GG infants have an enhanced capacity for processing both positive and negative socially meaningful contextual information, first amplifying and then differentially perpetuating negative affectivity in mothers who exhibit depressive characteristics.
Reducing ESA and service animal fraud
Authors: Masinter Michael R.
Published: November 2019

Occasionally students deliberately misrepresent their pets as emotional support animals, service dogs, or both. The internet is rife with scam sites that offer ESA letters for a fee, and some students have purchased letters from those sites. Adding to the problem, students living in residence halls with already approved ESA dogs sometimes claim they have trained their dog to be a psychiatric service dog, allowing them to take it to classes and meals. These students may simply show up with their dog in classrooms or campus food services with rehearsed but fraudulent answers to the two approved Department of Justice questions.
Mechanisms of the Reactions of B‐Substituted Amine Boranes with THF·BH3
Authors: Guo Yu , Wang Xinghua , Ma Nana , Cao Yilin , Hussain Sajjad , Zhang Jie , Wei Donghui , Chen Xuenian
Published: November 2019

The reactions of NH3BH2R (R = Me, Ph and Cl) with THFBH3 have been investigated and it was found that different substituents on the B atom help to proceed the reactions in different ways. The expected doubly‐bridged B‐substituted aminodiborane products, similar to aminodiborane (ADB, BH2(µ‐H)(µ‐NH2)BH2) via the reaction of ammonia borane (AB, NH3BH3) and tetrahydrofuran borane (THFBH3), are not obtained. Two competitive reactions occurred with the change of R = Me or Ph. When R is a Me group, an “open“ version of B‐substituted µ‐aminodiborane, THFBH(Me)(µ‐NH2)BH3, is formed as a major product; when R is a Ph group, AB and THFBH2Ph are formed as main products via the intermolecular NH3–THF exchange reaction. However, if R is Cl, then NH3BH2Cl reacts with THFBH3 through reversible intermolecular Cl–H exchange mechanism. Furthermore, DFT calculations are performed to elucidate the formation mechanism of THFBH(Me)(µ‐NH2)BH3 via the reaction of NH3BH2Me and THFBH3 as well as the exchange mechanism of Cl–H in the reaction of NH3BH2Cl and THFBH3.
In the Light and in the Dark: Photocatalytic Fixation of Nitrogen into Ammonia and Nitrate at Iron Titanate Semiconductor Thin Films
Authors: Kisch Horst
Published: November 2019

This Minireview first summarizes the principle of semiconductor photocatalysis focusing on the comparability of photocatalytic activities, a central problem of the field, often leading to unjustified mechanistic conclusions. It then describes the visible light photofixation of pure and aerial nitrogen at a nanostructured Fe2Ti2O7 thin film on glass. In the presence of ethanol or humic acid, ammonia is formed via hydrazine in the photochemical, first reaction part. Since only reducing agents exhibiting a current amplification effect enable ammonia formation, it is proposed that the primary reduction of N2 is a one‐photon – two‐electron proton‐coupled electron transfer. A consecutive aerial oxidation of ammonia to nitrate constitutes the thermally catalyzed final reaction part, indicating the dual catalysis function of the film. Since the over‐all reaction proceeds also with air, and weathering of corresponding iron titanium minerals could form Fe2Ti2O7 and similar semiconducting surfaces, a solar non‐enzymatic nitrogen fixation by natural reducing agents may occur in nature. This aspect of environmental chemistry is largely unexplored.
Polarization Effect on Regioselectivity of Pd‐Catalyzed Cyclization of 2‐Alkynylbenzaldehydes
Authors: Nardangeli Nolan , Topolovčan Nikola , Simionescu Razvan , Hudlický Tomáš
Published: November 2019

We report a study on the relationship between the polarization of C≡C bond in a series of 2‐alkynylbenzaldehydes and the regioselectivity of their Pd‐catalyzed annulation reactions. The electrophilic and nucleophilic character of the triple bond carbon atoms was examined using 13C and HMBC NMR experiments. The direction of polarization is determined only by the formyl group and its position on an aromatic ring. On the other hand, the strength of the polarization expressed through chemical shift difference Δδ of acetylenic carbon atoms is a result of electron‐withdrawing or electron‐donating ability of the other substituent. Out of two possible regioisomers, the Pd‐catalyzed cyclization reactions of 2‐alkynylbenzaldehydes that were studied predominantly afforded 1H‐isochromenes suggesting that the polarization of a triple bond is one of the contributing factors in the regioselectivity of this process.
N‐Alkoxyacrylamides in Domino Reactions: Catalytic and Stereoselective Access to δ‐Lactams
Authors: Champetter Philippe , Castillo‐Aguilera Omar , Taillier Catherine , Brière Jean‐François , Dalla Vincent , Oudeyer Sylvain , Comesse Sébastien
Published: November 2019

The first domino aza‐Michael/intramolecular‐Michael reaction employing acrylamides as key ambivalent partners for the synthesis of δ‐lactams is presented. It has been shown that the desired reactivity is contingent to the presence of an N‐alkoxy group within the acrylamides. Thus, in a base‐catalyzed process that operates under mild conditions, N‐alkoxyacrylamides are readily converted into polysubstituted δ‐lactams in good yields with good to excellent stereocontrol.
A New Approach for Voltammetric Determination of Nefopam and its Metabolite
Authors: Dubenska Liliya , Dushna Olha , Pysarevska Solomiya , Blazheyevskiy Mykola
Published: November 2019

In present paper we described a new simple voltammetric method of determination of nefopam alkaloid and its metabolite – N‐oxide. N‐oxide of nefopam is reduced at the dropping mercury electrode (DME) and silver solid amalgam electrodes (AgSAE), which can effectively replace mercury and chemically modified electrodes. The reduction consists of two one‐electron stages each accompanied with one proton transfer. N‐oxide of nefopam can be obtained from nefopam substance by oxidation with potassium peroxymonosulfate. It was studied the effect of various factors on N‐oxide quantitative yield (pH, oxidation duration, reagents concentration) as well as on the reduction of N‐oxide at DME and p‐AgSAE (pH, the nature of background electrolyte, potential and time of accumulation). It was showed that the reduction current linearly increased with increasing of concentration of analgesic. Limit of quantiation is 10−6 mol L−1 at DME and 10−7 mol L−1 at p‐AgSAE. The developed method was applied for the analysis of commercial drug solution for injection “Nefopam” with recovery of 96.7 %, as well as for the spiked human urine samples. Excellent repeatability with a relative standard deviation below 5 % was achieved.
High‐quality tweet generation for online behavior security management based on semantics measurement
Authors: Qin Tao , Wang Bo , Liu Zhaoli , Chen Zhouguo , Ding Jianwei
Published: November 2019

Behavior security management refers to monitoring and guiding the user's opinions in online social networks to reduce their harmful influence to social public security. Pushing designed tweets with specific contains to them is one of the promising ways to solve this problem. In this paper, we developed a new method for high‐quality supervision tweet generation, which not only considers the semantics of the tweets but also includes the supervision requirement of different aspects. Firstly, we collect millions of tweets of six typical events. Following, we construct a sentiment lexicon suitable for online behavior analysis, and we also construct a lexicon for tweet preprocessing and emotional score calculation. Secondly, to include the semantics during sentence similarity calculation, we employ the tweets collected to train the word2vec model and employ the sum of the word vectors in specific sentences to form the sentence vector. Finally, we employ the TextRank to generate the supervision tweet. Experimental results based on data collected showed that the proposed methods outperform other related traditional methods, which can be used for effective social security management.
Comparative study of two corrective gradient models in the simulation of multiphase flows using moving particle semi‐implicit method
Authors: Liu Xiaoxing , Morita Koji , Zhang Shuai
Published: November 2019

In this study, two corrective gradient models (CGMs) are compared in the simulation of multiphase flows. Linear consistency of the gradient model of moving particle semi‐implicit (MPS) method has been recovered by introducing corrective matrix. However, it is found that particles tend to disperse along the streamline while using the CGM proposed in a previous study. Particle shifting (PS) schemes are necessary to reduce the irregularity of particle distribution to stabilize the calculation. To enhance the accuracy and stability, another CGM with dummy particle (CGMD) was proposed in our previous study. This enhanced CGM is featured by linear consistency and purely repulsive pressure gradient force. In this study, this enhanced CGM is modified and applied to multiphase flow simulation. Comparative study suggests that the modified CGM with PS scheme is capable of calculating various multiphase flows and predicting the interface evolution both clearly and accurately.
Arbitrage opportunities, liquidity provision, and trader types in an index option market
Authors: Chen Chin‐Ho , Chiu Junmao , Chung Huimin
Published: November 2019

This study examines the impact of arbitrage in put–call futures parity (PCFP) violations on option market liquidity and explores the liquidity provision process by trader type during periods of arbitrage exploitation. Using a unique data set comprising the complete history of transactions, we find that PCFP violations contain toxic arbitrage opportunities. Hence, more frequent toxic arbitrage opportunities can cause liquidity to deteriorate because arbitrageurs create adverse selection costs and order imbalances in the option market. In addition, when the law of one price breaks down, market makers dominate by providing liquidity compared with individual, domestic, and foreign institutional traders.
Zircon U–Pb dating, geochemical, and Sr–Nd isotopic characteristics of Duobagou trachyandesite from Dunhuang, NW China: Implications for crust–mantle interaction
Authors: Wang Zhendong , Guo Zhaojie , Yu Xiangjiang , Zhang Yuanyuan
Published: November 2019

Comprehensive petrological, zircon U–Pb dating, whole‐rock geochemical, and Sr–Nd isotopic data are reported for the Duobagou volcanic rocks, intercalated with terrigenous clastic sequence, composing former Jurassic strata located at southeastern Dunhuang region, NW China. Duobagou volcanic interlayer is mainly composed of trachyandesite. LA–ICP–MS zircon dating yields a weighted mean 206Pb/238U age of 201.4 ± 3.4 Ma, affirming the formation of Late Triassic. The trachyandesites are characterized by enrichment of LREE relative to HREE with negative Eu, Sr, and Ti anomalies. The εNd(t) values (−0.24–1.91) and (87Sr/86Sr)i (0.7037–0.7049) shows an affinity of OIB. The Duobagou trachyandesite and Lucaogou basalt were proposed to be produced via 1–5% and 10–20% partial melting of the spinel–garnet‐bearing metasomatic enriched mantle and crystal fractionation coupled with slight extents of crustal contamination. Due to the delamination of thickened continental crust and asthenosphere upwelling, lower crustal material metasomatized and enriched the mantle source, leading to the eruption of trachyandesite. The Duobagou trachyandesite, Lucaogou sub‐alkaline basalt and thick sedimentary strata revealed that the Dunhuang region remained in an extension setting accompanied by rifting from Late Triassic to Middle Jurassic.
Differential effects of glucose deprivation on the survival of fetal versus adult neural stem cells‐derived oligodendrocyte precursor cells
Authors: Baldassarro Vito Antonio , Marchesini Alessandra , Giardino Luciana , Calzà Laura
Published: November 2019

Impaired myelination is a key feature in neonatal hypoxia/ischemia (HI), the most common perinatal/neonatal cause of death and permanent disabilities, which is triggered by the establishment of an inflammatory and hypoxic environment during the most critical period of myelin development. This process is dependent on oligodendrocyte precursor cells (OPCs) and their capability to differentiate into mature oligodendrocytes. In this study, we investigated the vulnerability of fetal and adult OPCs derived from neural stem cells (NSCs) to inflammatory and HI insults. The resulting OPCs/astrocytes cultures were exposed to cytokines to mimic inflammation, or to oxygen–glucose deprivation (OGD) to mimic an HI condition. The differentiation of both fetal and adult OPCs is completely abolished following exposure to inflammatory cytokines, while only fetal‐derived OPCs degenerate when exposed to OGD. We then investigated possible mechanisms involved in OGD‐mediated toxicity: (a) T3‐mediated maturation induction; (b) glutamate excitotoxicity; (c) glucose metabolism. We found that while no substantial differences were observed in T3 intracellular content regulation and glutamate‐mediated toxicity, glucose deprivation lead to selective OPC cell death and impaired differentiation in fetal cultures only. These results indicate that the biological response of OPCs to inflammation and demyelination is different in fetal and adult cells, and that the glucose metabolism perturbation in fetal central nervous system (CNS) may significantly contribute to neonatal pathologies. An understanding of the underlying molecular mechanism will contribute greatly to differentiating myelination enhancing and neuroprotective therapies for neonatal and adult CNS white matter lesions.
The effect of jaw exercises on anxiety and depression in patients with head and neck cancer receiving radiotherapy: Prospective 2‐year follow‐up study
Authors: Aghajanzadeh Susan , Karlsson Therese , Tuomi Lisa , Finizia Caterina
Published: November 2019

Background

This nonrandomized matched study investigates jaw exercise effect on anxiety/depressive symptoms in head and neck cancer patients with trismus during 2 years postradiotherapy.

Methods

Fifty patients with trismus postradiotherapy were included in a 10‐week jaw‐training intervention. A matched control group was included (N = 50). Maximum interincisal opening (MIO) ≤ 35 mm was used as the trismus criterion. Patients were assessed using MIO and Hospital Anxiety Depression Scale preintervention, postintervention, and at 2‐year follow‐up.

Results

A significant difference was found in depressive symptoms between the intervention group and control group (4% vs 33%) at 2‐year follow‐up, with more control group patients reporting possible depression. In the intervention group, significantly fewer patients had possible/probable depressive symptoms at follow‐up (4%) compared to preintervention (34%). No change was seen within the control group.

Conclusion

Structured jaw exercise in patients with postradiation trismus had positive effects on MIO and depressive symptoms but does not seem to have any significant effects on anxiety symptoms.
Managing knowledge for health care quality: An investigation of rational antibiotic use among Thai dentists
Authors: Pisarnturakit Pagaporn Pantuwadee , Sooampon Sireerat , Sooampon Sutti
Published: November 2019

Objectives

Because of the irrational use of antibiotics, antimicrobial resistance is now a global concern that requires developing effective strategies against. The aim of this study was to assess the knowledge gap that causes the irrational use of antibiotics among Thai dentists.

Methods

Thai dentists were asked to complete an online questionnaire regarding their knowledge, perception, and attitude towards rationale antibiotic use. The survey was conducted during November to December 2018.

Results

Online questionnaires were completed by 588 dentists. Most respondents had a positive perception and were aware of the rational use of antibiotics. However, the use of antibiotics without proper indication and the lack of pharmacological knowledge were found. A mobile application was considered the most preferable approach to manage knowledge for rational drug use.

Conclusion

Irrational drug use among Thai dentists can be caused by lack of knowledge, attitude, and the perception of each dentist. Policy makers should promote self‐learning through knowledge management strategies that can complement the pharmacology courses taught in dental school.
Analysis of weekend effect in severe acute liver injury: A nationwide database study
Authors: Do Albert , Ilagan‐Ying Ysabel C. , Taddei Tamar H.
Published: November 2019

Background and Aims

Severe acute liver injury (ALI) can lead to poor outcomes without timely management. Comparatively worse outcomes in various severe, emergent conditions have been attributed to reduced hospital resources experienced by patient weekend admissions, a phenomenon termed “weekend effect.” To date, a weekend effect has not been studied in severe ALI, an emergency also necessitating timely management. We aimed to evaluate such an effect in this condition by analyzing a large national inpatient database in the United States.

Methods

We analyzed the Nationwide/National Inpatient Sample (NIS) 2000 to 2014, the largest inpatient, all‐payer database in the United States (US), containing sociodemographic, clinical, patient‐, and hospital‐level data. We identified severe ALI using International Classification of Disease, 9th Revision diagnosis codes for acute/subacute hepatic necrosis (570) with encephalopathy (572.2). Our primary outcome was in‐hospital mortality. Using a full‐model approach for covariate selection, we performed multiple logistic regression modeling to assess for weekend effect and identify predictors of in‐hospital mortality.

Results

We identified 15 762 eligible hospitalizations, with 12 182 (77.3%) having complete covariate data. This sample comprised 53.3% males, 69.3% White race, and had an average (± SD) age of 55.0 ± 14.1 years. We utilized a full‐model approach for covariate inclusion but did not include patient transfer data due to limited availability. We observed no significant mortality differences in weekend admissions (OR = 1.06, 95% CI: 0.97‐1.15, P = 0.02). However, significantly higher mortality was associated with male sex, older age, Black or Hispanic race, Northeast US hospitalization, urban teaching status, and larger hospital size. Sensitivity analyses using multiple imputation datasets and transfer covariates did not change our results.

Conclusion

We did not observe a weekend effect of in‐hospital mortality for weekend admissions for severe ALI, but our overall diagnosis ascertainment yield was low—indicating that lack of accurate documentation for the etiology of severe ALI may be masking an effect. Additionally, our findings suggest that racial differences and hospital‐level characteristics in the context of severe ALI may be associated with varying outcomes, regardless of admission day, which warrants further research.
Cumulative exposure to premenopausal obesity and risk of postmenopausal cancer: A population‐based study in Icelandic women
Authors: Noh Hwayoung , Charvat Hadrien , Freisling Heinz , Ólafsdóttir Guðríður H. , Ólafsdóttir Elínborg J. , Tryggvadóttir Laufey , Arnold Melina , Soerjomataram Isabelle
Published: November 2019

Obesity, often assessed at one point in time, is an established risk factor of several types of cancer, however, associations with cumulative exposure to obesity across the life course are not well understood. We investigated the relationship between combined measures of duration and intensity of premenopausal overweight and obesity and the incidence of postmenopausal breast, endometrial, and colorectal cancers in Icelandic women. Body mass index (BMI) trajectories between ages 20 and 50 of 88,809 women from the Cancer Detection Clinic Cohort were predicted using growth curve models. Indicators of overweight and obesity duration and intensity were computed and their association with risk of postmenopausal breast, endometrial, and colorectal cancers was examined using multivariate Cox models for subjects followed‐up beyond the age of 50 (n = 67,488). During a mean follow‐up of 17 years, incident events of 3,016 postmenopausal breast, 410 endometrial and 987 colorectal cancers were ascertained. Each 0.1 kg/m2 per year increase in BMI between ages 20 and 50 was positively associated with risks of postmenopausal breast, endometrium and colorectal cancers with hazard ratios equal to 1.09 (95% Confidence Interval (CI):1.04–1.13), 1.31 (95% CI: 1.18–1.44) and 1.10 (95% CI: 1.00–1.21), respectively. Compared to women who were never obese, cumulative BMI × years of obesity were linearly positively associated with risk of endometrial cancer, whereas the association with breast cancer was initially positive, but leveled off with increasing cumulative BMI × years. Cumulative exposure to obesity may provide additional insights into the etiology of cancer and should be considered in future studies that assess obesity–cancer relationships.
Fabrication of porous carbonate apatite granules using microfiber and its histological evaluations in rabbit calvarial bone defects
Authors: Akita Kazuya , Fukuda Naoyuki , Kamada Kumiko , Kudoh Keiko , Kurio Naito , Tsuru Kanji , Ishikawa Kunio , Miyamoto Youji
Published: November 2019

Carbonate apatite (CO3Ap) granules are known to show good osteoconductivity and replaced to new bone. On the other hand, it is well known that a porous structure allows bone tissue to penetrate its pores, and the optimal pore size for bone ingrowth is dependent on the composition and structure of the scaffold material. Therefore, the aim of this study was to fabricate various porous CO3Ap granules through a two‐step dissolution–precipitation reaction using CaSO4 as a precursor and 30‐, 50‐, 120‐, and 205‐μm diameter microfibers as porogen and to find the optimal pore size of CO3Ap. Porous CO3Ap granules were successfully fabricated with pore size 8.2–18.7% smaller than the size of the original fiber porogen. Two weeks after the reconstruction of rabbit calvarial bone defects using porous CO3Ap granules, the largest amount of mature bone was seen to be formed inside the pores of CO3Ap (120) [porous CO3Ap granules made using 120‐μm microfiber] followed by CO3Ap (50) and CO3Ap (30). At 4 and 8 weeks, no statistically significant difference was observed based on the pore size, even though largest amount of mature bone was formed in case of CO3Ap (120). It is concluded, therefore, that the optimal pore size of the CO3Ap is that of CO3Ap (120), which is 85 μm.