bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Synthesis of Anthraquinones from Diaryl Carboxylic Acids via Palladium(II)‐Catalyzed and Visible Light‐Mediated Transformations
Authors: Kim Kiho , Min Minsik , Hong Sungwoo
Published: December 2016

Irradiation of 9‐ester‐substituted anthracenes with visible light results in the formation of endoperoxides in the absence of a photocatalyst, which further undergo base‐assisted fragmentation to afford anthraquinones. The excited state species of anthracene generated by energy transfer, interacts with 3O2 to afford 1O2 by energy transfer and undergoes cycloaddition with 1O2. By employing palladium(II)‐catalyzed and visible light‐mediated transformations, we have developed an efficient synthetic protocol for accessing diverse anthraquinones from readily available diaryl carboxylic acids. The optimal result was obtained with palladium(II) acetate, Ac‐Ile‐OH, benzoquinone and potassium carbonate in tert‐amyl alcohol under O2 at 90 °C with irradiation from a 30 W fluorescent light bulb.

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Direct ortho‐Trifluoroethylation of Aromatic Ureas by Palladium Catalyzed C‐H activation: A Missing Piece of Aromatic Substitutions
Authors: Kovács Szabolcs , Tóth Balázs L. , Borsik Gábor , Bihari Tamás , May Nóra V. , Stirling András , Novák Zoltán
Published: December 2016

Development of direct late‐stage installation of alkyl groups into aromatic systems is an important and challenging task of current organic chemistry. In spite of the existing functionalization methods in organic chemistry for the substitution reactions on aromatic systems, the direct alkylation of aromatic ureas is unknown. Herein, as a first example we report a novel palladium catalyzed fluoroalkylation process by C−H activation for the access of ortho trifluoroethylated aromatic ureas. The application of novel, highly active trifluoroethyl(mesityl)iodonium salt enables the efficient introduction of the trifluoroethyl group at 25 °C in 3 hours in high yields (up to 95%) with good functional group tolerance. DFT calculations have revealed a rate determining oxidative alkyl‐group transfer preceded by an unexpected C−H activation route on the Pd center during the catalytic cycle, where the deprotonation is assisted by an external triflate anion.

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Increased Toughness and Excellent Electronic Properties in Regioregular Random Copolymers of 3‐Alkylthiophenes and Thiophene
Authors: Smith Zachary C. , Wright Zoe M. , Arnold Anne M. , Sauvé Geneviève , McCullough Richard D. , Sydlik Stefanie A.
Published: December 2016

Lightweight, flexible, low‐cost, and disposable electronics have transformed modern life and promise to continue to drive a diversity of applications from defense to medicine. For flexible and stretchable devices, the mechanical demands are actually quite great, requiring a material to maintain its ability to undergo elastic deformation, in both tension and compression, through many cycles of deformation. Traditional electronics are fabricated using organic semiconductors, which offer excellent electronic performance, but are often stiff and brittle. Conductive polymers offer potential for electronic materials with high toughness and an ability to deform elastically, making inexpensive, flexible electronics possible in a way no other material can. This paper reports the bulk thermal, electronic, and mechanical properties of a series of conductive polymers based on regioregular poly(3‐alkylthiophenes) (P3ATs) with randomly incorporated polythiophene (PT) in 3:1 (P3AT3‐ran‐PT1) and 1:1 (P3AT1‐ran‐PT1) ratios. These random copolymers are synthesized with no added synthetic complexity with respect to the homopolymer, and reproducibly give polymers with dramatically different mechanical and electronic properties. It is shown that random incorporation of the unsubstituted thiophene results in conductive polymers with excellent electronic properties (conductivities up to 500 S/cm, mobilities up to 0.11 cm2 V−1 s−1) and enhanced toughness (up to 760% improvement).
Investigation of Energy Levels and Crystal Structures of Cesium Lead Halides and Their Application in Full‐Color Light‐Emitting Diodes
Authors: Van Le Quyet , Park Minjoon , Sohn Woonbae , Jang Ho Won , Kim Soo Young
Published: December 2016

Inorganic CsPbX3 perovskites with compositions including CsPbBrxCl3−x, CsPbBr3, and CsPbBrxI3−x are synthesized, and their properties are investigated. Tauc plots calculated from the UV–vis spectra of the materials show that the bandgaps of CsPbBrxCl3−x, CsPbBr3, and CsPbBrxI3−x are 2.7, 2.35, and 1.8 eV, respectively. The as‐prepared CsPbX3 nanodots have a cubic structure and their crystal sizes are around 5–10 nm. The diffraction peak intensity of the (110) plane is increased by adding Cl anion and reduced by adding I anion. By contrast, the peak intensity of the (200) plane is reduced by the introduction of Cl− ions and increased by the introduction of I− ions, suggesting that the nature of the halide anions affects the crystal orientation of CsPbX3 quantum dots. The highest occupied molecular orbital/lowest unoccupied molecular orbital levels of CsPbBrxCl3−x, CsPbBr3, and CsPbBrxI3−x calculated from ultraviolet photoemission spectra and UV–vis spectra are 6.5/3.8, 6.5/4.15, and 6.1/4.3 eV, respectively. The maximum luminance values measured for CsPbBrxCl3−x, CsPbBr3, and CsPbBrxI3−x‐based light‐emitting diodes (LEDs) are 15.2, 51.7, and 21.7 cd m−2, respectively. This research provides an overview of the energy levels and crystal structures of CsPbX3 quantum dots for the design of inorganic perovskite‐based LEDs with high luminance and power efficiencies.
Telesimulation: An Innovative Tool for Health Professions Education
Authors: McCoy Christopher Eric , Sayegh Julie , Alrabah Rola , Yarris Lalena M.
Published: December 2016

Telesimulation is a new and innovative concept and process that has been used to provide education, training, and assessment in health‐related fields such as medicine. This new area of simulation, and its terminology, has its origins within the past decade. The face validity and ability to provide the benefits of simulation education to learners at off‐site locations has allowed the wide and rapid adoption of telesimulation in the field of medical education. Telesimulation has been implemented in areas such as pediatric resuscitation, surgery, emergency medicine, ultrasound‐guided regional anesthesia in anesthesiology, nursing, and neurosurgery. However, its rapid expansion and current use has outgrown its recent description less than a decade ago. To date, there is no unifying definition of telesimulation that encompasses all the areas where it has been used while simultaneously allowing for growth and expansion in this field of study. This article has two main objectives. The first objective is to provide a comprehensive and unifying definition of telesimulation that encompasses all the areas where it has been used while allowing for growth and expansion in the field of study. The secondary objective is to describe the utility of telesimulation for emergency medicine educators in the context of the current evidence to serve as a background and framework that educators may use when considering creating educational programs that incorporate telecommunication and simulation resources. This article is complementary to the large group presentation where this new comprehensive and unifying definition was introduced to the simulation community at the International Meeting on Simulation in Healthcare in January 2016.
Ein stabiles neutrales Radikal in der Koordinationssphäre des Aluminiums
Authors: Li Bin , Kundu Subrata , Stückl A. Claudia , Zhu Hongping , Keil Helena , Herbst‐Irmer Regine , Stalke Dietmar , Schwederski Brigitte , Kaim Wolfgang , Andrada Diego M. , Frenking Gernot , Roesky Herbert W.
Published: December 2016

Das neuartige neutrale Radikal (Me2‐cAAC)2AlCl2 (2) wird durch cyclische Alkylaminocarbene (cAACs) stabilisiert. Die Synthese erfolgte in Gegenwart eines weiteren Äquivalents Me2‐cAAC durch Reduktion des Addukts Me2‐cAAC:AlCl3 (1) mit KC8. Anhand der Kristallstruktur zeigt sich, dass die beiden Carbene, die an das Aluminiumatom gebunden sind, deutlich unterschiedliche Al‐C‐Bindungen aufweisen. Dies lässt sich vermutlich auf die intermolekularen Wechselwirkungen zurückführen. Quantenmechanische Rechnungen ergaben dagegen eine Gleichgewichtsstruktur mit identischen Al‐C‐Bindungslängen. Verbindung 2 weist einen Monoradikalcharakter auf, der durch eine ESR‐Messung bestätigt werden konnte. Die Bindungsanalyse deutet darauf hin, dass das ungepaarte Elektron hauptsächlich am Carbenkohlenstoffatom lokalisiert ist. Somit ist 2 ein Beispiel für ein ungewöhnliches neutrales Al‐Radikal.
Polymersome Popping by Light‐Induced Osmotic Shock under Temporal, Spatial, and Spectral Control
Authors: Peyret Ariane , Ibarboure Emmanuel , Tron Arnaud , Beauté Louis , Rust Ruben , Sandre Olivier , McClenaghan Nathan D. , Lecommandoux Sebastien
Published: December 2016

The light‐triggered, programmable rupture of cell‐sized vesicles is described, with particular emphasis on self‐assembled polymersome capsules. The mechanism involves a hypotonic osmotic imbalance created by the accumulation of photogenerated species inside the lumen, which cannot be compensated owing to the low water permeability of the membrane. This simple and versatile mechanism can be adapted to a wealth of hydrosoluble molecules, which are either able to generate reactive oxygen species or undergo photocleavage. Ultimately, in a multi‐compartmentalized and cell‐like system, the possibility to selectively burst polymersomes with high specificity and temporal precision and to consequently deliver small encapsulated vesicles (both polymersomes and liposomes) is demonstrated.
Stereospecific Palladium‐Catalyzed Acylation of Enantioenriched Alkylcarbastannatranes: A General Alternative to Asymmetric Enolate Reactions
Authors: Wang Chao‐Yuan , Ralph Glenn , Derosa Joseph , Biscoe Mark R.
Published: December 2016

We report the development of a Pd‐catalyzed process for the cross coupling of unactivated primary, secondary, and tertiary alkylcarbastannatrane nucleophiles with acyl electrophiles. Reactions involving optically active alkylcarbastannatranes occur with exceptional stereofidelity and with net retention of absolute configuration. Because the stereochemistry of the resulting products is entirely reagent‐controlled, this process may be viewed as a general, alternative approach to the preparation of products typically accessed via asymmetric enolate methodologies. Additionally, we report a new method for the preparation of optically active alkylcarbastannatranes, which should facilitate their future use in stereospecific reactions.
Non‐Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co‐Delivery of Cas9 mRNA and sgRNA
Authors: Miller Jason B. , Zhang Shuyuan , Kos Petra , Xiong Hu , Zhou Kejin , Perelman Sofya S. , Zhu Hao , Siegwart Daniel J.
Published: December 2016

CRISPR/Cas is a revolutionary gene editing technology with wide‐ranging utility. The safe, non‐viral delivery of CRISPR/Cas components would greatly improve future therapeutic utility. We report the synthesis and development of zwitterionic amino lipids (ZALs) that are uniquely able to (co)deliver long RNAs including Cas9 mRNA and sgRNAs. ZAL nanoparticle (ZNP) delivery of low sgRNA doses (15 nm) reduces protein expression by >90 % in cells. In contrast to transient therapies (such as RNAi), we show that ZNP delivery of sgRNA enables permanent DNA editing with an indefinitely sustained 95 % decrease in protein expression. ZNP delivery of mRNA results in high protein expression at low doses in vitro (<600 pM) and in vivo (1 mg kg−1). Intravenous co‐delivery of Cas9 mRNA and sgLoxP induced expression of floxed tdTomato in the liver, kidneys, and lungs of engineered mice. ZNPs provide a chemical guide for rational design of long RNA carriers, and represent a promising step towards improving the safety and utility of gene editing.
Chemoselective Suzuki–Miyaura Cross‐Coupling via Kinetic Transmetallation
Authors: Fyfe James W. B. , Fazakerley Neal J. , Watson Allan J. B.
Published: December 2016

Chemoselective Suzuki–Miyaura cross‐coupling generally requires a designed deactivation of one nucleophile towards transmetallation. Here we show that boronic acids can be chemoselectively reacted in the presence of ostensibly equivalently reactive boronic acid pinacol (BPin) esters by kinetic discrimination during transmetallation. Simultaneous electrophile control allows sequential chemoselective cross‐couplings in a single operation in the absence of protecting groups.
Catalysis with Chalcogen Bonds
Authors: Benz Sebastian , López‐Andarias Javier , Mareda Jiri , Sakai Naomi , Matile Stefan
Published: December 2016

Herein, we introduce catalysts that operate with chalcogen bonds. Compared to conventional hydrogen bonds, chalcogen bonds are similar in strength but more directional and hydrophobic, thus ideal for precision catalysis in apolar solvents. For the transfer hydrogenation of quinolines and imines, rate enhancements well beyond a factor of 1000 are obtained with chalcogen bonds. Better activities with deeper σ holes and wider bite angles, chloride inhibition and correlation with computed anion binding energies are consistent with operational chalcogen bonds. Comparable to classics, such as 2,2′‐bipyrroles or 2,2′‐bipyridines, dithieno[3,2‐b;2′,3′‐d]thiophenes (DTTs), particularly their diimides, but also wide‐angle cyclopentadithiazole‐4‐ones are identified as privileged motifs to stabilize transition states in the focal point of the σ holes on their two co‐facial endocyclic sulfur atoms.
Expression of Epithelial and Mesenchymal Differentiation Markers in the Early Human Gonadal Development
Authors: Martinovic Vlatka , Vukusic Pusic Tanja , Restovic Ivana , Bocina Ivana , Filipovic Natalija , Saraga‐Babic Mirna , Vukojevic Katarina
Published: December 2016

Expressions of cytokeratin 8 (CK8), vimentin, nestin, and alpha‐smooth‐muscle‐actin (alpha‐SMA) were analyzed in the developing gonads of 12, 5–9 week old (W) human conceptuses by immunohistochemistry and immunofluorescence. During the investigated period, the number of CK8 positive cells increased from 56% to 92% in the gonadal surface epithelium, from 50% to 60% in the stroma, and from 23% to 42% in the medulla. In the early fetal period, the cell expression of CK8 increased in all gonadal parts, whereas primordial germ cells (PGC) remained negative. The expression of vimentin increased in the gonad stroma (gs) from 73% to 88%, and in the surface epithelium from 18% to 97% until ninth W. The medulla had the highest expression of vimentin in the seventh to eighth W (93%). Vimentin and CK8 colocalized in the somatic cells, while some PGCs showed vimentin expression only. Initially, nestin was positive in the gonad surface epithelium (8%) and stroma (52%), however during further development it decreased to 1% and 33%, respectively. In the early fetal period, the nestin positive cells decreased from 44% to 31% in the gonad medulla. Alpha‐SMA was positive only in the blood vessels and mesonephros. The described pattern of expression of intermediate filaments (IF) in developing human gonads suggests their role in the control of PGC apoptosis, early differentiation of gs cells and cell migration. Both epithelial and mesenchymal origins of follicular cells and possible epithelial‐to‐mesenchymal transition of somatic cells is proposed. Lastly, IF intensity expression varies depending on the cell type and developmental period analyzed. Anat Rec, 300:1315–1326, 2017. © 2017 Wiley Periodicals, Inc.
Competition and regulation in a new integrated transit system across jurisdictional borders
Authors: Du Haoming , Gao Ziyou , Ren Hualing
Published: December 2016

It is often argued lately that some regional transit systems should be integrated to improve the transit services across jurisdictional borders. One of the important issues concerning this integrated transit system is how to make proper use of the competition and regulation to improve its performance and to increase relevant benefits to the authorities, the operators and the passengers. This paper deals with this problem in a new integrated transit system across jurisdictional borders. An optimization model is used to investigate the competition of transit operators in oligopolistic competition transit market (OCTM). An optimization model with nonlinear complementarity constraints is proposed to guide the competition of transit operators using transit subsidy as the regulation means in system optimum transit system (SOTM). By analyzing and comparing the performances of the integrated transit system in two markets, numerical studies show that the competition mechanism should be made full use of and transit subsidy is an important regulation means that should be valued by the transit authorities in the integrated transit system. Copyright © 2016 John Wiley & Sons, Ltd.
Life cycle analysis of corn‐stover‐derived polymer‐grade l‐lactic acid and ethyl lactate: greenhouse gas emissions and fossil energy consumption
Authors: Adom Felix K. , Dunn Jennifer B.
Published: December 2016

Co‐production of high‐value chemicals with biofuels could improve the economic viability of biorefineries while reducing biofuel life‐cycle greenhouse gas (GHG) emissions and fossil energy consumption (FEC). Polymer‐grade lactic acid (PGLA) is a high‐potential bioproduct currently produced from first‐generation feedstocks. Opportunity exists to enhance its environmental performance using cellulosic feedstocks. Moreover, ethyl lactate can be used as a functional replacement for high‐volume, energy‐intensive, and emissions‐intensive petroleum‐derived chemicals such as N‐methyl‐2‐pyrrolidone and ethyl acetate. Based on material and energy flows from Aspen Plus process models that we incorporated into the Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET) model's bioproducts module, we developed life‐cycle GHG emissions and FEC estimates for ethyl lactate and PGLA produced from corn stover. We compared these results to those for fossil‐fuel‐derived counterparts, identified key LCA drivers, and explored the impact of end‐of‐life assumptions on LCA results. Irrespective of the end‐of‐life assumption, all the bioproducts demonstrated lower life‐cycle FEC (10–72%) and GHG emissions (23–90%) than fossil‐derived compounds for which they could serve as a functional replacement. Additionally, we reviewed the role of LCA in three major bioproduct sustainability certification schemes (the BioPreferred Program, the Roundtable on Sustainable Biomaterials, and International Sustainability and Carbon Certification Plus). None mandate an LCA of the bioproduct to assess whether, across the supply chain, these products offer environmental benefits as compared to conventional chemicals they could displace either directly or functionally. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Evaluation of drug efficacy of DPP‐4 inhibitors based on theoretical analysis with pharmacokinetics and pharmacodynamics
Authors: Takayanagi Risa , Uchida Takumi , Kimura Koji , Yamada Yasuhiko
Published: December 2016

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are used clinically as therapeutic agents for the treatment of diabetes. To determine the rate of DPP‐4 inhibition induced by these inhibitors, pharmacokinetic and pharmacodynamic parameters were used to theoretically examine the relationship between the rate of DPP‐4 inhibition and clinical efficacy following the administration of four different DPP‐4 inhibitors (sitagliptin, vildagliptin, alogliptin, linagliptin) by focusing on the increase in the level of glucagon‐like peptide‐1 (GLP‐1) induced by their administration. On the basis of the relationship shown, changes in clinical efficacy in association with dose change were examined in order to discuss clinical dosage from the standpoint of proper usage. The results indicate that a high rate of DPP‐4 inhibition is necessary for the onset of the effect of an administered the DPP‐4 inhibitor and that the average value for the DPP‐4 inhibition rate can be utilized as a common parameter of clinical efficacy. Furthermore, the efficacy profiles of the present DPP‐4 inhibitors could be demonstrated on the basis of an increase in the GLP‐1 level. It is considered that the present findings provide useful information for promoting the proper clinical use of DPP‐4 inhibitors. Copyright © 2016 John Wiley & Sons, Ltd.
LC–high‐resolution–MS/MS analysis of chemical compounds in rat plasma after oral administration of Nao‐Mai‐Tong and its individual herbs
Authors: Rong Yueying , Feng Suxiang , Wu Chunwei , Wang Shumei , Liang Shengwang , Liu Dongyun
Published: December 2016

Nao‐Mai‐Tong (NMT), a Chinese herbal formula, is used for treating ischemia cerebral apoplexy. To discover the components of NMT with potential in vivo bioactivity and investigate the differences between NMT and its single herb components, this study rigorously compared plasma samples collected from rats dosed with NMT and single‐herb extracts at different times through LC‐high resolution–MS/MS and data processing (Metworks). The plasma of the NMT group contained a total of 66 identified compounds (25 prototypes and 41 metabolites), including anthraquinones, triterpenoid saponins, isoflavones and phthalides. Additionally, glucuronidation, sulfation and cysteine conjugation were the major reactions through which the compounds in NMT were metabolized. The comparison of the groups revealed two metabolites that were only detected in the plasma from the NMT‐dosed group, whereas seven prototype ingredients (chrysophanol‐8‐O‐glucoside, ginsenoside Rf, Rg2, Rh1, F1, F2 and chikusetsusaponin IVa) and 12 metabolites (two novel triterpenoid saponins) were only discovered in the plasma samples from the single‐herb‐dosed groups. Moreover, the trends in the chemical compounds detected presented marked differences between NMT‐dosed rat plasma and plasma samples from the single‐herb‐dosed groups. The above data indicate that prescription compatibility affects the assimilation and elimination of ingredients and provides useful information for further pharmacokinetic studies.
Simultaneous UPLC‐MS/MS determination of antiepileptic agents for dose adjustment
Authors: Farouk Faten , ElKady Ehab F. , Azzazy Hassan M. E.
Published: December 2016

Therapeutic 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.
Characterization of TAP Ambr 250 disposable bioreactors, as a reliable scale‐down model for biologics process development
Authors: Xu Ping , Clark Colleen , Ryder Todd , Sparks Colleen , Zhou Jiping , Wang Michelle , Russell Reb , Scott Charo
Published: December 2016

Demands for development of biological therapies is rapidly increasing, as is the drive to reduce time to patient. In order to speed up development, the disposable Automated Microscale Bioreactor (Ambr 250) system is increasingly gaining interest due to its advantages, including highly automated control, high throughput capacity, and short turnaround time. Traditional early stage upstream process development conducted in 2 ‐ 5 L bench‐top bioreactors requires high foot‐print, and running cost. The establishment of the Ambr 250 as a scale‐down model leads to many benefits in process development. In this study, a comprehensive characterization of mass transfer coefficient (kLa) in the Ambr 250 was conducted to define optimal operational conditions. Scale‐down approaches, including dimensionless volumetric flow rate (vvm), power per unit volume (P/V) and kLa have been evaluated using different cell lines. This study demonstrates that the Ambr 250 generated comparable profiles of cell growth and protein production, as seen at 5‐L and 1000‐L bioreactor scales, when using kLa as a scale‐down parameter. In addition to mimicking processes at large scales, the suitability of the Ambr 250 as a tool for clone selection, which is traditionally conducted in bench‐top bioreactors, was investigated. Data show that cell growth, productivity, metabolite profiles, and product qualities of material generated using the Ambr 250 were comparable to those from 5‐L bioreactors. Therefore, Ambr 250 can be used for clone selection and process development as a replacement for traditional bench‐top bioreactors minimizing resource utilization during the early stages of development in the biopharmaceutical industry. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:478–489, 2017
Modeling and simulation practices for a computational thinking‐enabled engineering workforce
Authors: Magana Alejandra J. , Silva Coutinho Genisson
Published: December 2016

Computational 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
Review best practices for navigating legally treacherous situations
Authors: Boone Kathleen C.
Published: December 2016

If the current legal and compliance climate has you feeling under siege, you're certainly not alone. Nearly 300 postsecondary institutions are presently subject to review by the Office for Civil Rights. During the past several years, “Dear Colleague Letters” and other high‐level policy guidance and regulations have proliferated, along with regular news reports of yet another finding of violations on the part of yet another college or university.
Reduce risk by addressing aging equipment, facilities
Authors: O'Brien Timothy
Published: December 2016

Athletics departments' continued use of aging facilities and equipment raises critical fiscal and legal issues for colleges and universities.
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

Research 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.
Identification of Predominant Phytochemical Compounds and Cytotoxic Activity of Wild Olive Leaves (Olea europaea L. ssp. sylvestris) Harvested in South Portugal
Authors: Makowska‐Wąs Justyna , Galanty Agnieszka , Gdula‐Argasińska Joanna , Tyszka‐Czochara Małgorzata , Szewczyk Agnieszka , Nunes Ricardo , Carvalho Isabel S. , Michalik Marta , Paśko Paweł
Published: December 2016

This study has been aimed at providing a qualitative and quantitative evaluation of selected phytochemicals such as phenolic acids, flavonoids, oleuropein, fatty acids profile, and volatile oil compounds, present in wild olive leaves harvested in Portugal, as well as at determining their antioxidant and cytotoxic potential against human melanoma HTB‐140 and WM793, prostate cancer DU‐145 and PC‐3, hepatocellular carcinoma Hep G2 cell lines, as well as normal human skin fibroblasts BJ and prostate epithelial cells PNT2. Gallic, protocatechuic, p‐hydroxybenzoic, vanillic acids, apigenin 7‐O‐glucoside, luteolin 7‐O‐glucoside, and rutin were identified in olive leaves. The amount of oleuropein was equal to 22.64 g/kg dry weight. (E)‐Anethole (32.35%), fenchone (11.89%), and (Z)‐3‐nonen‐1‐ol (8%) were found to be the main constituents of the oil volatile fraction, whereas palmitic, oleic, and alpha‐linolenic acid were determined to be dominating fatty acids. Olive leaves methanol extract was observed to exerted a significant, selective cytotoxic effect on DU‐145 and PC‐3 cell lines. Except the essential oil composition, evaluated wild olive leaves, with regard to their quantitative and qualitative composition, do not substantially differ from the leaves of other cultivars grown for industrial purposes and they reveal considerable antioxidant and cytotoxic properties. Thus, the wild species may prove to be suitable for use in traditional medicine as cancer chemoprevention.
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

Two 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

Rosbin (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

MicroRNA‐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

Immunotherapy 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 Message

We 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

A 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

Overproduction 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

Betaine 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

An 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

Benzylic 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

Li18P6N16 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

Lower 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.