bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous UPLC‐MS/MS determination of antiepileptic agents for dose adjustment
Authors: Farouk Faten , ElKady Ehab F. , Azzazy Hassan M. E. 
Published: December 2016

AbstractTherapeutic drug monitoring (TDM) of anti‐epileptic drugs (AED) is a routine application. Carbamazepine (CRB) is monitored as the parent drug while oxcarbazepine (OXC) and eslicarbazepine acetate (ESL) are monitored as their active metabolite (eslicarbazepine; MHD). We have developed a UPLC‐MS/MS method for determining CRB, OXC, ESL and MHD in plasma or serum with a simplified extraction protocol. The developed method detects sildenafil (SLD), which clinically interferes with AED and is likely to be co‐administered in epileptic patients suffering from sexual insufficiency (60%). MHD was prepared in‐house. AED were simultaneously determined in presence of SLD using gatifloxacin as an internal standard (IS). Separation was achieved using acetonitrile, methanol and 100 mm ammonium acetate in water (32:3:65, v/v/v) on an Intersil®RP‐HPLC column (250 × 4.6 mm, 5 μm). A one‐step extraction was performed by simultaneous protein and phospholipids precipitation. Detection was done by tandem mass spectrometry. No relative matrix effect was observed. The method was linear (0.5–40 μg/mL for CRB, ESL and MHD and 0.05–4 μg/mL for OXC), accurate and selective. Recoveries were 64.41 ± 5.07, 45.62 ± 1.73, 61.41 ± 4.77 and 60.33 ± 1.36 for CRB, OXC, ESL and MHD, respectively. The method was successfully applied for TDM of AED.
Modeling and simulation practices for a computational thinking‐enabled engineering workforce
Authors: Magana Alejandra J. , Silva Coutinho Genisson 
Published: December 2016

ABSTRACTComputational thinking has been recognized as a collection of understandings and skills required for new generations of students not only proficient at using tools, but also at creating them and understanding the implication of their capabilities and limitations. This study proposes the combination of modeling and simulation practices along with disciplinary learning as a way to synergistically integrate and take advantage of computational thinking in engineering education. This paper first proposes a framework that identifies different audiences of computing and related computational thinking practices at the intersection of computer science and engineering. Then, based on a survey with 37 experts from industry and academia, this paper also suggests a series of modeling and simulation practices, methods, and tools for such audiences. Finally, this paper also reports experts’ identified challenges and opportunities for integrating modeling and simulation practices at the undergraduate level. © 2016 Wiley Periodicals, Inc. Comput Appl Eng Educ 25:62–78, 2017; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21779
Contact, Political Solidarity and Collective Action: An Indian Case Study of Relations between Historically Disadvantaged Communities
Authors: Dixon John , Cakal Huseyin , Khan Waheeda , Osmany Meena , Majumdar Sramana , Hassan Mudassir 
Published: December 2016

AbstractResearch on the contact hypothesis has highlighted the role of contact in improving intergroup relations. Most of this research has addressed the problem of transforming the prejudices of historically advantaged communities, thereby eroding wider patterns of discrimination and inequality. In the present research, drawing on evidence from a cross‐sectional survey conducted in New Delhi, we explored an alternative process through which contact may promote social change, namely by fostering political solidarity and empowerment amongst the disadvantaged. The results indicated that Muslim students' experiences of contact with other disadvantaged communities were associated with their willingness to participate in joint collective action to reduce shared inequalities. This relationship was mediated by perceptions of collective efficacy and shared historical grievances and moderated by positive experiences of contact with the Hindu majority. Implications for recent debates about the relationship between contact and social change are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
Identification of Glucosinolates in Seeds of Three Brassicaceae Species Known to Hyperaccumulate Heavy Metals
Authors: Montaut Sabine , Guido Benjamin S. , Grison Claude , Rollin Patrick 
Published: December 2016

Plants from the Brassicaceae family are known to contain secondary metabolites called glucosinolates. Our goal was to establish by LC/MS the glucosinolate profile of seeds of three Brassicaceae species known to hyperaccumulate heavy metals. We investigated Alyssum fallacinum auct. non Hausskn., Iberis intermedia Guers., and Noccaea caerulescens (J. Presl & C. Presl) F. K. Mey. Our results indicate that A. fallacinum seeds contain glucoiberin and glucoibervirin, which had not been previously identified in this plant. Furthermore, we report for the first time the presence of glucoiberin, glucoibervirin, glucotropaeolin, and sinigrin in I. intermedia. We have detected for the first time glucoconringiin in N. caerulescens. In addition, glucosinalbin, 4‐hydroxyglucobrassicin, and glucomoringin were also detected.
Polar Hinges as Functionalized Conformational Constraints in (Bi)cyclic Peptides
Authors: van de Langemheen Helmus , Korotkovs Valerijs , Bijl Joachim , Wilson Claire , Kale Sangram S. , Heinis Christian , Liskamp Rob M. J. 
Published: December 2016

AbstractTwo polar hinges for cyclization of peptides have been developed, leading to bicyclic peptides and cyclized peptides with improved solubility and biological activity. Increasingly, we note that a good aqueous solubility of peptides is an absolute prerequisite, not only to allow handling and purification of our target peptides but also being crucial for biological activity characteristics. Compared to earlier hinges, the 1,1′,1“‐(1,3,5‐triazinane‐1,3,5‐triyl)tris(2‐bromoethanone) (TATB) and 2,4,6‐tris(bromomethyl)‐s‐triazine (TBMT), each containing three nitrogen atoms are structurally similar but chemically very different. Both were accessible in a one‐step fashion from bromoacetonitrile. TATB and TBMT are very suitable for the preparation of more soluble bicyclic peptides. Azide‐modified TATB and TBMT derivatives provide hinges for the preparation of cyclized peptides for incorporation on scaffolds to afford protein mimics.
Rosbin, a synthetic small molecule, induces A549 cells apoptosis through a ROS‐mediated pathway
Authors: Zhao Ting , Jin Wenling , Pan Hui , Li Haizhou , Zhao Yang , Feng Yang 
Published: December 2016

AbstractRosbin (Thieno [2, 3‐c] piperidine‐3‐carboxamide‐2‐[(3‐methoxy‐naphtha‐lene‐2‐carbonyl)‐amino]‐6‐(benzyl)‐, hydrochloride), a synthetic piperidinothieno derivative compound obtained from chemical genetics screenings, significantly suppresses the viability of non‐small cell lung cancer A549 cells with an IC50 of 2.05 ± 0.31 µM. It only decreases growth of non‐tumour MRC‐5 cells at the doses higher than 10 µM. Rosbin induces apoptosis in a dose‐dependent manner by reducing the mitochondrial membrane potential (MMP) and increasing activities of caspases‐3/7 and caspase‐9 in A549 cells, without affecting the activity of caspase‐8. Further studies showed that reactive oxygen species (ROS) induced apoptosis of A549 in the presence of rosbin as apoptosis was inhibited by N‐acetyl cysteine (NAC). These results suggest that rosbin is a novel apoptosis inducer, and ROS played a significant role in the A549 apoptosis induced by rosbin.
miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts
Authors: Xu Shun , Zhang Bing , Zhu Yanmei , Huang Haijiao , Yang Wenping , Huang Haiyong , Zheng Hui‐ling , Liu Xinguang 
Published: December 2016

AbstractMicroRNA‐194 (miR‐194), a typical p53 responsive miRNA, serves as a tumor suppressor similar as p53, and has been demonstrated to play an anti‐proliferation role in various human cancers. In spite of the pivotal role of p53 during aging process, the knowledge of miR‐194's contribution to cellular senescence is limited. We herein sought to explore the role of miR‐194 in the replicative senescence and stress‐induced senescence of mouse embryonic fibroblasts. Our results unraveled that, compared to young cells, miR‐194 is highly expressed in senescent cells, and extra expression of miR‐194 significantly triggers the replicative senescence of MEFs and H2O2‐induced senescence of NIH/3T3 cells, while inhibition of miR‐194 exhibited the opposite effect. We further unveiled that DNMT3A was a direct and authentic target of miR‐194, which has been reported to be closely associated with cellular senescence. Taken together, our data suggest that miR‐194 may significantly promote the development of cellular senescence in mouse embryonic fibroblasts, which potentially occurs through inhibiting the DNMT3A expression.
Bladder cancer cells induce immunosuppression of T cells by supporting PD‐L1 expression in tumour macrophages partially through interleukin 10
Authors: Wang Xingyuan , Ni Shaobin , Chen Qiyin , Ma Li , Jiao Zhixing , Wang Chunyang , Jia Guang 
Published: December 2016

AbstractImmunotherapy based on BCG vaccination is an effective treatment in bladder cancer, but a positive response is restricted to a subset of patients and for a limited period of time only. This suggests that T cells antitumour responses are effective but can become compromised in bladder cancer. To investigate the underlying mechanisms, we first identified peripheral blood monocytes and tumour macrophages using the pan‐monocyte/macrophage marker CD14, and found that the PD‐L1 expression on the monocytes/macrophages in bladder cancer patients was significantly higher than that in controls. The monocytes from bladder cancer patients were also more capable at inducing apoptosis and inhibiting proliferation in activated autologous T cells than monocytes from controls, which was directly associated with the level of PD‐L1 expression. We next investigated the tumour cells’ participation in upregulating PD‐L1 in monocytes/macrophages. Significant elevation of PD‐L1 was observed in monocytes after culturing with autologous tumour cells, which did not require direct contact but required soluble factors. The STAT phosphorylation pattern in monocytes after tumour cell co‐culture was consistent with effects of the interleukin (IL)‐10 signalling pathway. We then found that removal of IL‐10 in monocyte‐tumour cell co‐culture reduced the PD‐L1 upregulation in monocytes, but IL‐10 by itself was unable to directly upregulate PD‐L1. Primary bladder tumour cells secreted significant levels of IL‐10, indicating that they could serve as the source of IL‐10. Together, these results demonstrated a novel pathway that bladder cancer cells induced immunosuppression of T cells by supporting PD‐L1 expression in tumour macrophages partially through IL‐10.
Extracorporeal membrane oxygenation rescue in adolescent with bronchiolitis obliterans‐organizing pneumonia like Wegener's granulomatosis
Authors: Falk Lars , Broman Lars Mikael 
Published: December 2016

Key Clinical MessageWe report a 17‐year‐old woman with bronchiolitis obliterans‐organizing pneumonia (BOOP)‐like granulomatosis with polyangiitis developing severe airway obliterations. Pending age, phase and grade of autoimmune treatment, and offering ECMO treatment may be crucial for survival but occasionally preface futility. ECMO‐treated patient with BOOP‐like GPA has never been described before.
Structure‐Activated Copper Photosensitisers for Photocatalytic Water Reduction
Authors: Chen Nan‐Yu , Xia Liang‐Min , Lennox Alastair J. J. , Sun Yuan‐Yuan , Chen Hao , Jin Hai‐Ming , Junge Henrik , Wu Qin‐An , Jia Jian‐Hong , Beller Matthias , Luo Shu‐Ping 
Published: December 2016

AbstractA series of phenanthroline‐based ligands have been synthesised and their influence as bidentate nitrogen ligands in heteroleptic [Cu(P^P)(N^N)]+ photosensitisers in light‐driven water reduction has been studied. In this noble‐metal‐free Cu–Fe‐based photocatalytic water reduction system, the structural effects of the nitrogen ligands have been explored, including the steric and electronic effects of substituents at the 2,9‐ and 4,7‐positions of phenanthroline. Ligands were prepared that led to increased hydrogen generation, with turnover numbers (TONCu) of up to 1388 being observed. All the new complexes were electrochemically and photophysically characterised. We demonstrate for the first time that the presence of fluorine in nitrogen ligands increases the efficacy of copper complexes in photocatalytic hydrogen production.
Imaging Extracellular Lactate In Vitro and In Vivo Using CEST MRI and a Paramagnetic Shift Reagent
Authors: Zhang Lei , Martins André F. , Mai Yuyan , Zhao Piyu , Funk Alexander M. , Clavijo Jordan M. Veronica , Zhang Shanrong , Chen Wei , Wu Yunkou , Sherry A. Dean 
Published: December 2016

AbstractOverproduction of lactate is a hallmark of cancer, yet a method to quantitatively measure lactate production by cancer cells is not straight‐forward. Chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) can potentially be used to image lactate but the small difference in chemical shift of the lactate −OH proton and water proton resonances make it challenging. Like other spectroscopic methods, CEST MRI cannot discriminate intracellular lactate from extracellular lactate. Herein, we demonstrate a relatively simple way to shift the lactate −OH proton resonance far away from water by addition of the paramagnetic shift reagent, EuDO3A, while retaining the CEST properties of lactate itself. The potential of the method was demonstrated by imaging extracellular lactate excreted from lung cancer cells in tissue culture without interference from other components in the culture media and by imaging excess lactate excreted into the bladder of a mouse.
Exploring the Solvatochromism of Betaine 30 with Ab Initio Tools: From Accurate Gas‐Phase Calculations to Implicit and Explicit Solvation Models
Authors: Budzák Šimon , Jaunet‐Lahary Titouan , Laurent Adèle D. , Laurence Christian , Medved' Miroslav , Jacquemin Denis 
Published: December 2016

AbstractBetaine 30 is known for the extraordinary solvatochromism of its visible absorption band that goes from λ=882 nm in tetrachloromethane to λ=453 nm in water (Δλ=−429 nm). This large blueshift partly originates from a dramatic decrease of the dipole moment upon excitation. Despite several decades of research, experimental works still disagree on the exact value of the excess dipole moment, the orientation of the dipole moment of the excited‐state, the role and amplitude of the change of the polarisability upon excitation as well as on the gas‐phase excitation energy. In this work, we present an in‐depth theoretical investigation. First, we carefully tested several levels of theory on the model system and next calculated the electric properties of betaine 30 at the CC2 level. Our best estimates are Δμ=−7 D for the excess dipole moment, that is, a significant decrease but no change of direction, a Δα value of −120 a.u. and a gas‐phase vertical excitation energy of 1.127 eV. The implicit solvation models are able to reproduce the experimental trends, with large correlation coefficients for non‐hydrogen‐bond‐donating solvents, the smallest root‐mean‐square deviation error being reached with the vertical excitation model (VEM). The explicit effective fragment potential method combined with time‐dependent density functional theory (TD‐DFT) in a QM/MM framework provides accurate estimates for hydrogen‐bond‐donating solvents, whereas the addition of a dispersion correction is needed to restore the correct solvatochromic direction in tetrachloromethane.
Ab Initio Crystal Field for Lanthanides
Authors: Ungur Liviu , Chibotaru Liviu F. 
Published: December 2016

AbstractAn ab initio methodology for the first‐principle derivation of crystal‐field (CF) parameters for lanthanides is described. The methodology is applied to the analysis of CF parameters in [Tb(Pc)2]−(Pc=phthalocyanine) and Dy4K2 ([Dy4K2O(OtBu)12]) complexes, and compared with often used approximate and model descriptions. It is found that the application of geometry symmetrization, and the use of electrostatic point‐charge and phenomenological CF models, lead to unacceptably large deviations from predictions based on ab initio calculations for experimental geometry. It is shown how the predictions of standard CASSCF (Complete Active Space Self‐Consistent Field) calculations (with 4f orbitals in the active space) can be systematically improved by including effects of dynamical electronic correlation (CASPT2 step) and by admixing electronic configurations of the 5d shell. This is exemplified for the well‐studied Er‐trensal complex (H3trensal=2,2′,2“‐tris(salicylideneimido)trimethylamine). The electrostatic contributions to CF parameters in this complex, calculated with true charge distributions in the ligands, yield less than half of the total CF splitting, thus pointing to the dominant role of covalent effects. This analysis allows the conclusion that ab initio crystal field is an essential tool for the decent description of lanthanides.
Highly Enantioselective Ferrocenyl Palladacycle‐Acetate Catalysed Arylation of Aldimines and Ketimines with Arylboroxines
Authors: Schrapel Carmen , Frey Wolfgang , Garnier Delphine , Peters René 
Published: December 2016

AbstractBenzylic N‐substituted stereocenters constitute a frequent structural motif in drugs. Their highly enantioselective generation is hence of technical importance. An attractive strategy is the arylation of imines with organoboron reagents. Chiral Rh complexes have reached a high level of productivity for this reaction type. In this article we describe that an electron rich PdII catalyst also performs well in the arylation of aldimines, comparable to the best Rh catalysts. The ferrocenyl palladacycle‐acetate catalyst allows for a broad substrate scope and very high enantioselectivities. Commonly observed side reactions like aryl–aryl homocouplings and imine hydrolysis could be blocked. Mechanistic studies implicate that a) the acetate ligand is crucial for transmetallation, b) the active catalyst is most likely a palladacycle‐OAc monomer, c) the rate limiting step is probably the product release. By added KOAc the arylation could also be applied to ketimines.
Li18P6N16—A Lithium Nitridophosphate with Unprecedented Tricyclic [P6N16]18− Ions
Authors: Bertschler Eva‐Maria , Dietrich Christian , Janek Jürgen , Schnick Wolfgang 
Published: December 2016

AbstractLi18P6N16 was synthesized by reaction of LiPN2 and Li7PN4 at 5.5 GPa and 1273 K employing the multi‐anvil technique. It is the first lithium nitridophosphate obtained by high‐pressure synthesis. Moreover, it is the first example received by reaction of two ternary lithium nitrides. The combination of high‐pressure conditions with a Li3N flux enabled a complete structure determination using single‐crystal X‐ray diffraction. The hitherto unknown tricyclic [P6N16]18− anion is composed of six vertex‐sharing PN4 tetrahedra forming one vierer‐ and two additional dreier‐rings. To confirm the structure, Rietveld refinement, 7Li and 31P solid‐state NMR spectroscopy, FTIR spectroscopy and EDX measurements were carried out. To validate the ionic properties, the migration pathways of the Li+ ions were evaluated, and the conductivity and its temperature dependence were determined by impedance spectroscopy measurements. In order to obtain a clearer picture of the formation mechanism of this compound class, different synthetic approaches were compared, enabling targeted syntheses of unprecedented P/N‐anion topologies with intriguing properties.
Expanding Water/Base Tolerant Frustrated Lewis Pair Chemistry to Alkylamines Enables Broad Scope Reductive Aminations
Authors: Fasano Valerio , Ingleson Michael J. 
Published: December 2016

AbstractLower Lewis acidity boranes demonstrate greater tolerance to combinations of water/strong Brønsted bases than B(C6F5)3, this enables Si−H bond activation by a frustrated Lewis pair (FLP) mechanism to proceed in the presence of H2O/alkylamines. Specifically, BPh3 has improved water tolerance in the presence of alkylamines as the Brønsted acidic adduct H2O–BPh3 does not undergo irreversible deprotonation with aliphatic amines in contrast to H2O–B(C6F5)3. Therefore BPh3 is a catalyst for the reductive amination of aldehydes and ketones with alkylamines using silanes as reductants. A range of amines inaccessible using B(C6F5)3 as catalyst, were accessible by reductive amination catalysed by BPh3 via an operationally simple methodology requiring no purification of BPh3 or reagents/solvent. BPh3 has a complementary reductive amination scope to B(C6F5)3 with the former not an effective catalyst for the reductive amination of arylamines, while the latter is not an effective catalyst for the reductive amination of alkylamines. This disparity is due to the different pKa values of the water–borane adducts and the greater susceptibility of BPh3 species towards protodeboronation. An understanding of the deactivation processes occurring using B(C6F5)3 and BPh3 as reductive amination catalysts led to the identification of a third triarylborane, B(3,5‐Cl2C6H3)3, that has a broader substrate scope being able to catalyse the reductive amination of both aryl and alkyl amines with carbonyls.
Proof of Principle: Immobilisation of Robust CuII3TbIII‐Macrocycles on Small, Suitably Pre‐functionalised Gold Nanoparticles
Authors: Feltham Humphrey L. C. , Dumas Christophe , Mannini Matteo , Otero Edwige , Sainctavit Philippe , Sessoli Roberta , Meledandri Carla J. , Brooker Sally 
Published: December 2016

AbstractInvited for the front cover of this issue is the multi‐national collaborative team of Carla Meledandri, Roberta Sessoli, Sally Brooker and co‐workers at the Universities of Otago and Florence along with IMPMC and SOLEIL. The image depicts the binding of huge amounts of macrocyclic complexes onto small monodisperse gold nanoparticles prefunctionalised by carboxylate tethers. Read the full text of the article at 10.1002/chem.201604821.
A Ring‐Opening Metathesis Polymerization Catalyst That Exhibits Redox‐Switchable Monomer Selectivities
Authors: Lastovickova Dominika N. , Shao Huiling , Lu Gang , Liu Peng , Bielawski Christopher W. 
Published: December 2016

AbstractA ring‐opening metathesis polymerization catalyst supported by a redox‐active N‐heterocyclic carbene was synthesized and found to undergo reversible reduction. In its neutral form, the catalyst polymerized 1,5‐cis,cis‐cyclooctadiene at a higher rate than that of a norbornene derivative; however, upon reduction, the selectivity was found to reverse. Utilizing this oxidation state dependent selectivity, a series of copolymers with controlled compositions, microstructures, and physical properties were prepared by redox‐switching the catalyst over the course of a series of polymerization reactions.