bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated numerical and experimental framework for modeling of CTB and GD1b ganglioside binding kinetics
Authors: Lee Dongheon , Singla Akshi , Wu Hung‐Jen , Kwon Joseph Sang‐Il
Published: May 2018

A mathematical model is developed and validated for a multistep binding process between cholera toxin subunit B (CTB) and GD1b receptors that precedes cholera infection. To study the dynamics of the complex CTB‐GD1b binding mechanisms, cooperative binding effect and GD1b receptor aggregation in the host cell membrane are considered. More reliable parameters for the CTB‐GD1b binding kinetics are estimated by quantitatively calibrating the proposed multistep binding model against the experimental measurements obtained from the novel nanocube‐based biosensor. Specifically, a numerical scheme that includes the sensitivity analysis, parameter estimation and dynamic optimization is implemented for the model calibration. Through this scheme, identifiable model parameters are determined. After those selected parameters are estimated, the calibrated model and the experimental measurements were in reasonable agreement for different CTB and GD1b concentrations, which shows a promising approach for identification of the kinetics of CTB binding to the host cell membrane. © 2018 American Institute of Chemical EngineersAIChE J, 64: 3882–3893, 2018
Retardation of the phase segregation of liquid mixtures with a critical point of miscibility
Authors: Califano Filomena , Mauri Roberto
Published: May 2018

The phase transition extraction (PTE) process consists of bringing a partially miscible mixture from the single‐phase to the two‐phase region of its phase diagram. Its most important characteristic is that the resulting phase separation is very fast, and hardly affected by coalescence‐retarding impurities. In this work we study two counter‐cases, where the PTE process appears to be severely retarded. First, we consider the ouzo effect, where the mixture forms very stable metastable micro‐emulsions, showing that this process can be generalized, leading to a reverse ouzo effect, where a modifier is added in large quantities. The second retardation technique consists of using very viscous solvents. We found that, in agreement with the predictions of the phase field model, the growth rate of the nuclei during the initial stage of phase separation does not depend on viscosity, while, on the other hand, when the size of the nuclei exceed their capillary length, gravitational effects become relevant and the settling time is proportional to the viscosity of the continuous phase. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4047–4052, 2018
An optimization framework to combine operable space maximization with design of experiments
Authors: Chen Qi , Paulavičius Remigijus , Adjiman Claire S. , García‐Muñoz Salvador
Published: May 2018

The introduction of Quality by Design in the pharmaceutical industry stimulates practitioners to better understand the relationship of materials, processes and products. One way to achieve this is through the use of targeted experimentation. In this study, an optimization framework to design experiments that effectively leverage parameterized process models is presented to maximize the space covered in the output variables while also obtaining an orthogonal bracketing study in the process input factors. The framework considers both multi‐objective and bilevel optimization methods for relating the two maximization objectives. Results are presented for two case studies—a spray coating process and a continuously stirred reactor cascade—demonstrating the ability to generate and identify efficient designs with fit‐for‐purpose trade‐offs between bracketed orthogonality in the input factors and volume explored in the process output space. The proposed approach allows a more complete understanding of the process to emerge from a small set of experiments. © 2018 The Authors. AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.AIChE J, 64: 3944–3957, 2018
Chemoenzymatic Assembly of Mammalian O‐Mannose Glycans
Authors: Meng Caicai , Sasmal Aniruddha , Zhang Yan , Gao Tian , Liu Chang‐Cheng , Khan Naazneen , Varki Ajit , Wang Fengshan , Cao Hongzhi
Published: May 2018

O‐Mannose glycans account up to 30 % of total O‐glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O‐mannose glycans of α‐dystroglycan, which are a causative factor for various muscular diseases. In this study, a highly efficient chemoenzymatic strategy was developed that enabled the first collective synthesis of 63 core M1 and core M2 O‐mannose glycans. This chemoenzymatic strategy features the gram‐scale chemical synthesis of five judiciously designed core structures, and the diversity‐oriented modification of the core structures with three enzyme modules to provide 58 complex O‐mannose glycans in a linear sequence that does not exceed four steps. The binding profiles of synthetic O‐mannose glycans with a panel of lectins, antibodies, and brain proteins were also explored by using a printed O‐mannose glycan array.
Methyl methacrylate based copolymers and terpolymers: Preparation, identification, and plasticizing capability for a poly(methyl methacrylate) used in aviation
Authors: Atabaki Fariborz , Shokrolahi Arash , Pahnavar Zohreh
Published: May 2018

In this study, we first synthesized transparent poly(methyl methacrylate–maleic anhydride) [P(MMA–MAH)] and poly(methyl methacrylate–maleic anhydride–N‐2‐methyl‐4‐nitrophenyl maleimide) [P(MMA–MAH–MI)] via free‐radical polymerization at different monomer ratios. The synthesized polymers were characterized by titration, viscometric, spectroscopy, and thermal analyses. Higher contents of maleic anhydride (MAH) resulted in increases in the viscosity, glass‐transition temperature (Tg), and transparency. The synthesized polymers were then blended with a commercial‐grade poly(methyl methacrylate) (PMMA) used in aviation in the presence of CHCl3. According to the free volume theory, the incorporation of 5 wt % P(MMA–MAH)s or P(MMA–MAH–MI)s into the commercial PMMA resulted in a plasticizing impact on this thermoplastic, which was confirmed by the decrease in the Tg values of the blends with almost the same transparency as the initial PMMA. In fact, the higher the content of MAH was, the lower the Tg of the blends was. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46603.
Characterization of ketoprofen‐loaded PEG‐CH semi‐IPN system for wound dressing application
Authors: Gaitán‐Tolosa Ibeth M. , Montiel‐Campos Raúl , Flores‐Estrada Jaime , Domínguez‐García Ma. Victoria , Flores‐Merino Miriam V.
Published: May 2018

Polymer systems, in the form of crosslinking networks, have been widely used in biomedicine. However, they are a challenge mainly due to the impact of their physicochemical properties on release kinetics of drugs. Ketoprofen is an analgesic anti‐inflammatory drug with short half‐life (<2 h) and quickly eliminated by the body. Topical administration of ketoprofen can reduce pain, accelerate the wound healing process, and minimize the risk of systemic side effects. Therefore, the aim was to synthesize, characterize, and evaluate a novel ketoprofen polymer system in the form of a semi‐interpenetrated network of poly(ethylene glycol)‐chitosan. The pore size studied by small‐angle X‐ray scattering showed the presence of nanoscale pores, 13.7 nm (dry state) and 26.18 nm (swollen form). The maximum swelling was 420 ± 45% at 24 h. Finally, the encapsulated ketoprofen (6.5%) was released at a constant concentration (0.12 ± 0.03 mg/mL, 8 h) and half of the doses up to 24 h. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46644.
Chitosan hydrogel‐coated cotton fabric: Antibacterial, pH‐responsiveness, and physical properties
Authors: Trad Mariem , Miled Wafa , Benltoufa Sofien , Boughattas Amal , Benslama Rihab , Fayala Faten , Bakhrouf Amina
Published: May 2018

In this work, chitosan hydrogel has been synthesized and used to impart pH‐sensitivity and antimicrobial finish to cotton fabric. In order to enhance the incorporation rate of hydrogel, anionic, and cationic activation of the textile surface was applied and then compared. The antibacterial activity of the fabric was then studied. The results revealed an enhancement of the antibacterial activities of the modified fabrics against Escherichia coli, Listeria monocytogene, and Staphylococcus aureus bacteria's. The capacity of material to respond to pH change was studied and confirmed using contact angle method. The anionic fabric treated with hydrogel showed a better pH‐responsiveness. Scanning electron microscopic testing results has also confirmed that the deposition of hydrogel was clearly better with the anionic activation. The characteristics of breathability of the fabrics were analyzed. The results show that the moisture management behavior of the finished materials is significantly better than the control one. Although the permeability to air has reduced by 10%, the permeability to water vapor remained practically unchanged. Furthermore, the effects of the antibacterial finishing on the physical properties of the cotton fabrics were also investigated. It was established that the functionalized samples have changed structure parameters, thickness, air permeability, tensile strength, and resistance to wrinkles. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46645.
Flexible conductive poly(styrene‐butadiene‐styrene)/carbon nanotubes nanocomposites: Self‐assembly and broadband electrical behavior
Authors: Ferreira Santos João Paulo , França Melo Guilherme Henrique , Gonçalves André Marino , Eiras José Antonio , Suman Bretas Rosario Elida
Published: May 2018

Flexible conductive nanocomposites with the ability of self‐assembly into well‐ordered structures are promising multifunctional materials for energy conversion and storage devices. In this work, flexible nanocomposites based on multi‐walled carbon nanotubes (MWCNTs) and poly(styrene‐butadiene‐styrene) (SBS) were obtained by solution casting, followed by a post‐annealing treatment, during 7 days at 110 °C, to enable the self‐organization of the SBS. The impact of the MWCNTs on the self‐assembly was studied by atomic force microscopy and Small angle X‐rays scattering, and the conductivity of these nanocomposites was analyzed over the broadband frequency range, that is, 10−1–106 Hz. The results revealed that the lower MWCNTs loadings (∼0.2 v %) were the most suitable to achieve a conductive network through the SBS, maintaining self‐assembled domains. These domains include hexagonally packed cylinders and alternating lamellae. Furthermore, at loadings above 1 v %, the impact of further MWCNTs addition on the conductivity was marginal over the whole frequency range and the self‐assembly tendency was progressively reduced. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46650.
In situ grafting onto solution polymerized styrene butadiene rubbers (SSBR) filled with silica via solid state method
Authors: Wang Lili , Lu Yonglai , Xie Ximing , Zheng Fangyuan
Published: May 2018

Grafting reaction of solution polymerized styrene butadiene rubbers (SSBR) and 3‐mercaptopropionic acid in situ was investigated in a solid state and a series of SSBR with different polarity degree were prepared through grafting 3‐mercaptopropionic acid onto SSBR chains in the process of mixing. The feasibility of solid‐phase grafting in situ (SPGiS) was verified by 1H‐nuclear magnetic resonance and Fourier transform infrared spectroscopy. Compared with unmodified SSBR/silica compounds, the SSBR/silica compounds with SPGiS exhibited preferable performance in silica dispersion, rubber‐filler interaction, and reinforcing efficiency. The scanning electron microscope and transmission electron microscope showed that silica presented better dispersion and smaller aggregates in the SSBR of SPGiS. Dynamical mechanical analysis of vulcanized rubber compounds with SPGiS showed that the wet skid resistance and the rolling resistance of SSBR/silica compounds were improved separately. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46653.
Poly(vinyl alcohol)–lignin blended resin for cellulose‐based composites
Authors: Ko Hyun‐U , Zhai Lindong , Park Jung Ho , Lee Ji Yun , Kim Debora , Kim Jaehwan
Published: May 2018

Wood has limitations in strength because of its biostructural defects, including vessels. To overcome this limitation, composite materials can be innovated by breaking wood down into cellulose and lignin and reassembling them for bio‐originating strong structural materials. In this study, an ecofriendly resin was developed that was suitable for cellulose‐based composites. To overcome the low dimensional stability of lignin and to increase its interactions with cellulose, it was blended with poly(vinyl alcohol) (PVA). The PVA–lignin resin was characterized with scanning electron microscopy, Fourier transform infrared spectroscopy, thermal analysis, mechanical tensile testing, and lap‐shear joint testing. The adhesion properties of the PVA–lignin resin increased with increasing PVA content. PVA played the role of synthetic polymer and that of linker between the cellulose and lignin, like hemicellulose does in wood. The PVA–lignin resin exhibited a high miscibility, mechanical toughness, and good adhesion properties for nanocellulose composites. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46655.
Epoxy resin/phosphorus‐based microcapsules: Their synergistic effect on flame retardation properties of high‐density polyethylene/graphene nanoplatelets composites
Authors: Xia Yanping , Tang Rui , Tao Shengxi , Tao Guoliang , Gong Fanghong , Liu Chunlin , Cao Zheng
Published: May 2018

Two types of microcapsule flame retardants are prepared by coating ammonium polyphosphate (APP) and aluminum diethylphosphinate (ADP) with epoxy resin (EP) as the shell via in situ polymerization, and blended with high density polyethylene (HDPE)/graphene nanoplatelets (GNPs) composites to obtain flame‐retardant HDPE materials. Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), and water contact angle results confirm the formation of core–shell structures of EP@APP and EP@ADP. The limiting oxygen index (LOI), vertical burning test (UL‐94), cone calorimetry, and Raman spectroscopy are employed to characterize the HDPE/GNPs composites filled with EP@APP and EP@ADP core–shell materials. A UL94 V‐0 level and LOI of 34% is achieved, and the two flame retardants incorporated in the HDPE/GNPs composite at 20 wt % in total play a synergistic effect in the flame retardancy of the composite at a mass ratio of EP@ADP:EP@APP = 2:1. According to the cone‐calorimetric data, the compounding composites present much lower peak heat release rate (300 kW/m2) and total heat release (99.4 MJ/m2) than those of pure HDPE. Raman spectroscopic analysis of the composites after combustion reveals that the degree of graphitization of the residual char can reach 2.31, indicating the remarkable flame retarding property of the composites. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46662.
Bumping, precedents, and de‐escalation in South China Sea: Options for the United States and China
Authors: Vuković Siniša , Alfieri Riccardo
Published: May 2018

The article departs from a much needed clarification about the 2 overlapping conflicts in South China Sea: sovereignty dispute between China and ASEAN countries, and freedom of navigation dispute between China and the United States. Although both are well documented and covered by an extensive range of academic and policy‐relevant analyses, the lines between the 2 have often been blurred, yielding a very limited set of options for proper conflict management. This paper looks at the actual reasons behind Chinese defiance toward the United States, and how can this be reversed. In order to avoid a potential clash in the South China Sea, this paper looks at how similar situations, where the United States was challenging the excessive maritime claims of other nuclear powers, were managed peacefully in light of an inevitable clash. A surprisingly underscrutinized precedent of “bumping incident” form 1988, when U.S. Navy vessels were rammed by Soviet ships and “bumped” back to the international waters is used as a template for a potential solution in the ongoing Sino‐American conflict. This paper examines the limits and opportunities of this type of solution and shows how another “bumping incident” does not need to happen before a bilateral solution is explored.
Impact of Dean Vortices on the Integrity Testing of a Continuous Viral Inactivation Reactor
Authors: Amarikwa Linus , Orozco Raquel , Brown Matthew , Coffman Jon
Published: May 2018

We propose a standard protocol for integrity testing the residence‐time distribution (RTD) in a “Jig in a Box” design (JIB)—a previously described tortuous‐path, tubular, low‐pH, continuous viral inactivation reactor, ensuring that biopharmaceutical products will be incubated for the required minimum residence time, tmin . tmin is the time by which just 0.001% of the total product containing virus has exited the incubation chamber (i.e., t0.00001). This t0.00001 is selected to ensure a >4‐log reduction in viral load. As current tracers and in‐line analytical technologies may not be able to detect tracers at the 0.001% level, an alternative approach is required. The authors describe a method for deriving tmin from t0.005 (i.e., the time at which 0.5% of the product has emerged from the reactor outlet) and an experimentally confirmed offset value, toffset = t0.005−t0.00001. The authors also evaluate tracer candidates—including 100‐nm‐diameter gold nanoparticles, dextrose, monoclonal antibody, and riboflavin—for pre‐process acceptability and the effects of viscosity, molecular diffusion coefficient, and particle size. The authors show that a JIB will yield tmin and RTDs that are nearly identical for multiple tracers due to Dean vortex induced mixing. Results indicate that almost any small‐molecule tracer that is generally recognized as safe can be used in pre‐use integrity testing of a continuous viral inactivation reactor under the Deans values (De) of 119–595.
Sprouted and Freeze‐Dried Wheat and Oat Seeds – Phytochemical Profile and in Vitro Biological Activities
Authors: Aborus Naji Elhadi , Šaponjac Vesna Tumbas , Čanadanović‐Brunet Jasna , Ćetković Gordana , Hidalgo Alyssa , Vulić Jelena , Šeregelj Vanja
Published: May 2018

This research was carried out to study phytochemical profile, in vitro antioxidant capacity, reducing power, anti‐hyperglycemic, anti‐inflammatory activities and simulated gastrointestinal digestion of 7‐day old cereal sprouts: spelt wheat ‘Nirvana’ (WSSpe), wheat ‘Simonida’ (WSSim), oat ‘Golozrni’ (OSG) and oat ‘Jadar’ (OSJ). OSG expressed significantly higher (P ≤ 0.05) total phenols (TPC) and flavonoids content (TFC), antioxidant capacities (DPPH and ABTS assays) and reducing power (EC50DPPH = 2.12 mg/ml; EC50ABTS = 0.87 mg/ml; EC0.5RP = 12.24 mg/ml) as well as anti‐hyperglycemic activity (EC50AHgA = 0.96 mg/ml). WSSpe had the highest content of chlorophyll (131.23 mg/100 g) and carotenoids (22.84 mg/100 g). WSSim possessed the most potent anti‐inflammatory activity (2.71 mg/ml), though not significantly different from OSG (2.77 mg/ml). The in vitro simulation of gastro‐intestinal digestion showed higher release of phenolic compounds in intestinal than in gastric fluid.
Quercetin, Kaempferol and Isorhamnetin in Elaeagnus pungens Thunb. Leaf: Pharmacological Activities and Quantitative Determination Studies
Authors: Zhu Ji‐Xiao , Wen Le , Zhong Wei‐Jin , Xiong Li , Liang Jian , Wang Hong‐Ling
Published: May 2018

Elaeagnus pungens leaf was documented to be very effective to treat asthma and chronic bronchitis both as traditional Chinese medicine and minority traditional medicine; yet the actual effective components still remain unknown. This work is to investigate the anti‐inflammatory, antalgic and antitussive activities of E. pungens leaf, quercetin and kaempferol, and their contents in E. pungens leaf. Pharmacological experiments showed that they could considerably reduce ear‐swelling of mouse and relieve writhing reaction of mouse; they could also prevent mouse from coughing significantly. These findings suggested that quercetin and kaempferol are major effective components treating asthma and chronic bronchitis. Quantitative analysis results indicated that the levels of quercetin, kaempferol and isorhamnetin varied greatly in different species of Elaeagnus and in different plant parts: E. pungens leaf is more similar to Elaeagnus umbellate leaf chemically; quercetin level is exceptionally high in Elaeagnus oldhami leaf; E. pungens leaf is a better medical part for treating asthma and chronic bronchitis in comparison with other parts.
Sesquiterpene Synthase‐Catalysed Formation of a New Medium‐Sized Cyclic Terpenoid Ether from Farnesyl Diphosphate Analogues
Authors: Huynh Florence , Grundy Daniel J. , Jenkins Robert L. , Miller David J. , Allemann Rudolf K.
Published: May 2018

Terpene synthases catalyse the first step in the conversion of prenyl diphosphates to terpenoids. They act as templates for their substrates to generate a reactive conformation, from which a Mg2+‐dependent reaction creates a carbocation–PPi ion pair that undergoes a series of rearrangements and (de)protonations to give the final terpene product. This tight conformational control was exploited for the (R)‐germacrene A synthase– and germacradien‐4‐ol synthase–catalysed formation of a medium‐sized cyclic terpenoid ether from substrates containing nucleophilic functional groups. Farnesyl diphosphate analogues with a 10,11‐epoxide or an allylic alcohol were efficiently converted to a 11‐membered cyclic terpenoid ether that was characterised by HRMS and NMR spectroscopic analyses. Further experiments showed that other sesquiterpene synthases, including aristolochene synthase, δ‐cadinene synthase and amorphadiene synthase, yielded this novel terpenoid from the same substrate analogues. This work illustrates the potential of terpene synthases for the efficient generation of structurally and functionally novel medium‐sized terpene ethers.
Transcriptional noise in intact and TGF‐beta treated human kidney cells; the importance of time‐series designs
Authors: Rabieian Reyhaneh , Moein Shiva , Khanahmad Hossein , Mortazavi Mojgan , Gheisari Yousof
Published: May 2018

The transforming growth factor (TGF)‐β signaling pathway plays a key role in various cellular processes. However, insufficient knowledge about the complex and sometimes paradoxical functions of this pathway hinders its therapeutic targeting. In this study, the transcriptional profile of seven mediators and downstream elements of the TGF‐β pathway were assessed in TGF‐β treated and untreated human kidney derived cells for 2 weeks in a time course manner. As expected the up‐regulation of ACTA2 and COL1A2 was evident in the treated cells. However, we observed remarkable fluctuations in gene expression, even in the supposedly steady states. The magnitude of noise was diverse in the examined genes. Our findings underscore the significance of time‐course designs for gene expression analyses and clearly show that misleading data can be obtained in single point measurements. Furthermore, we propose specific considerations in the interpretation of time‐course data in the context of noisy gene expression.
Stepwise Methane‐to‐Methanol Conversion on CuO/SBA‐15
Authors: Le Ha V. , Parishan Samira , Sagaltchik Anton , Ahi Hamideh , Trunschke Annette , Schomäcker Reinhard , Thomas Arne
Published: May 2018

The direct partial oxidation of methane to methanol is a challenging scientific and economical objective to expand the application of this abundant fuel gas as a major resource for one‐step production of value‐added chemicals. Despite substantial efforts to commercialize this synthetic route, to date no heterogeneous catalyst can selectively oxidize methane to methanol by O2 with an economically acceptable conversion. Cu‐exchanged zeolites have been recently highlighted as one of the most promising bioinspired catalysts toward the direct production of methanol from methane under mild conditions. In this work, Cu‐based catalysts were prepared using mesoporous silica SBA‐15 as an alternative support and their activity for this conversion was investigated. The results demonstrate that highly dispersed CuO species on SBA‐15 are able to react with methane and subsequently produce methanol with high selectivity (>84 %) through water‐assisted extraction. Furthermore, it was confirmed that the main intermediate formed after interaction of the catalyst with methane is a methoxyl species, which can be further converted to methanol or dimethyl ether on extraction with water or methanol, respectively.
Si@C Microsphere Composite with Multiple Buffer Structures for High‐Performance Lithium‐Ion Battery Anodes
Authors: Li Yankai , Liu Wenbo , Long Zhi , Xu Pengyuan , Sun Yang , Zhang Xiaokang , Ma Shuhua , Jiang Ning
Published: May 2018

In this work, a Si@C microsphere composite with multiple buffer structures is prepared by hydrothermal treatment to solve the fatal drawbacks of serious pulverization and low electronic conductivity of Si anodes. By virtue of ferric citrate being the carefully chosen coating carbon source, the silicon nanoparticles with a SiOx layer are encapsulated by the homogeneous mesoporous carbon layer. The SiOx layer with appropriate toughness can primarily suppress the volume expansion of silicon. The plentiful mesopores in the carbon layer and the framework formed by carbon nanotubes with good mechanical strength can effectively buffer and accommodate the volume change of silicon, and greatly improve the infiltration of the electrolyte to the anode. Meanwhile, the mesoporous carbon and carbon nanotube network also enhance the conductivity of the composite. Therefore, the Si@C electrodes exhibit a high initial charge/discharge capacity of 2956/4197 mAh g−1 at a current density of 0.42 A g−1, excellent rate capability, and outstanding cycle performance up to 800 cycles by virtue of the multiple buffer structures.
A Dipyrrin Programmed for Covalent Loading with Fullerenes
Authors: Li Chengjie , Wurst Klaus , Kräutler Bernhard
Published: May 2018

We describe here a di‐(β,β′‐sulfoleno)pyrrin programmed for efficient and specific β,β′‐functionalization via [4+2] cycloaddition reactions. At 120 °C and in the presence of an excess of C60‐fullerene the di‐(β,β′‐sulfoleno)pyrrin decomposed cleanly, furnishing a di‐(β,β′‐fullereno)pyrrin and the corresponding monofullereno‐dipyrrin in an overall yield of 96 %. Hence, relatively mild thermolysis of the di‐(β,β′‐sulfoleno)pyrrin induced stepwise extrusion of two equivalents of SO2, producing highly reactive dipyrrin‐β,β′‐diene intermediates readily, providing a very effective path to [4+2]‐cycloadducts. As presented here by the example of the covalent attachment of C60‐fullerene units, a convenient general methodology for the efficient synthesis of covalent dipyrrin β,β′‐cycloadducts is made available.
Using the Relative Energy Gradient Method with Interacting Quantum Atoms to Determine the Reaction Mechanism and Catalytic Effects in the Peptide Hydrolysis in HIV‐1 Protease
Authors: Thacker Joseph C. R. , Vincent Mark A. , Popelier Paul L. A.
Published: May 2018

The reaction mechanism in an active site is of the utmost importance when trying to understand the role that an enzyme plays in biological processes. In a recently published paper [Theor. Chem. Acc. 2017, 136, 86], we formalised the Relative Energy Gradient (REG) method for automating an Interacting Quantum Atoms (IQA) analysis. Here, the REG method is utilised to determine the mechanism of peptide hydrolysis in the aspartic active site of the enzyme HIV‐1 Protease. Using the REG method along with the IQA approach we determine the mechanism of peptide hydrolysis without employing any arbitrary parameters and with remarkable ease (albeit at large computational cost: the system contains 133 atoms, which means that there are 17 689 individual IQA terms to be calculated). When REG and IQA work together it is possible to determine a reaction mechanism at atomistic resolution from data directly derived from quantum calculations, without arbitrary parameters. Moreover, the mechanism determined by this novel method gives concrete insight into how the active site residues catalyse peptide hydrolysis.
Synthesis of 1‐Aminoindenes through Aza‐Prins‐Type Cyclization
Authors: Bai Jian‐Fei , Yasumoto Kento , Kano Taichi , Maruoka Keiji
Published: May 2018

An acid‐catalyzed aza‐Prins‐type endo cyclization of 2‐alkenylbenzaldehydes with BocNH2 or aniline derivatives through in situ generation of iminium intermediates has been developed, and various 1‐aminoindene derivatives were readily obtained. The first catalytic asymmetric variant of the present reaction has also been demonstrated.
A Highly Stable Framework of Crystalline Zinc Phosphite with Selective Removal, Recovery, and Turn‐On Sensing Abilities for Mercury Cations in Aqueous Solutions
Authors: Wang Chih‐Min , Lin Yong‐Jie , Pan Ming‐Feng , Su Cheng‐Kuan , Lin Tai‐Yuan
Published: May 2018

A highly stable framework of organic‐inorganic hybrid zinc phosphite (NTOU‐4) and its cobalt analogue (NTOU‐4a) were synthesized under the hydro(solvo)thermal conditions and structurally characterized by single‐crystal X‐ray diffraction. Their frameworks consisted of inorganic metallophosphite chains, in which the metal atoms were interlinked through 1H‐1,2,4‐triazole‐3,5‐diamine and 1,4‐benzenedicarboxylate linkers to form new crystalline materials. It is extremely difficult to achieve the consolidation of three distinct coordinations of metal‐carboxylate, metal‐triazolate, and metal‐phosphite bonds into one crystal, resulting in the synthesis of the first mixed‐ligand terephthalate‐metallophosphite solids in the absence of organic molecules as templates or space‐filling counters in their structures. Interestingly, the zinc compound not only exhibits high thermal stability (up to 400 °C in air) and chemical resistance to seawater, aqueous solutions (pH 3–11), and organic solvents at boiling conditions, but also shows selective removal, recovery, and “turn‐on” sensing abilities of toxic mercury ions in aqueous solutions. Furthermore, the synthesis, characterization, and the difference of the framework stabilities between isostructural zinc and cobalt compounds are also reported.
Phosphine‐Relayed Aldehyde‐Olefination and Aza‐Wittig Reaction with 2,2,2‐Trifluorodiazoethane
Authors: Zhang Fa‐Guang , Lv Ning , Zheng Yan , Ma Jun‐An
Published: May 2018

Phosphine‐relayed olefination and aza‐Wittig reactions of readily available aldehydes with 2,2,2‐trifluorodiazoethane (CF3CHN2) have been realized. This protocol enables the facile construction of a series of trifluoromethylated alkenes and hydrazones in good to high yield under mild conditions.
Bioactive Alkaloids from Indole‐3‐carbinol Exposed Culture of Daldiniaeschscholzii
Authors: Lin Li Ping , Tan Ren Xiang
Published: May 2018

Two new and rare bioactive indoles named dalesindoloids A (1) and B (3), along with 3‐(1H‐indole‐3ylmethyl)‐2‐oxindole (2), were characterized from the indole‐3‐carbinol (I3C)‐exposed culture of Daldinia eschscholzii. The absolute configuration of 2 was determined by quantum chemical calculations of the electronic circular dichroism (ECD) spectrum. Dalesindoloids A and B were cytotoxic against the leukemia HL‐60 cell line with the IC50 values of 1.0 and 7.4 μmol/L, respectively, with the former being inhibitory on Staphylococcus aureus (MIC: 9.1 μmol/L). The simultaneous characterization of the alkaloids from the I3C‐exposed fungal culture highlighted that the 2,3‐epoxyindoline motif can be transformed into both lactam and indolin‐3‐one moieties. This is the first‐time description of the 2,3‐epoxyindoline chemical versatility and Wagner‐Meerwein rearrangement (WMR) reaction in the microbial culture.
Advances in DNA Origami Nanopores: Fabrication, Characterization and Applications
Authors: Ren Yong‐An , Gao Han , Ouyang Xiangyuan
Published: May 2018

In recent years, bio‐nanopore and solid‐state nanopore have been greatly improved for molecule bio‐sensing. Whereas, the development of this scientific field seems to have encountered a bottleneck due to their respective limitations. The small pore size of the former impedes the detection of large single molecule, and the latter is difficult to achieve similar accuracy and functional control. DNA origami plays a novel role to bring more opportunities for the development of nanopore technology since it is relatively easy to synthesize and modify. This review mainly focuses on introducing the DNA origami nanopore fabrication methods, characterization and application. Meanwhile, the challenges in the present DNA origami nanopore research are also discussed.
Prevalence and outcome of patients referred for chest pain with high‐sensitivity troponin elevation and no diagnosis at discharge
Authors: Lordet Vincent , Lesbordes Matthieu , Garcia Rodrigue , Varroud‐Vial Nicolas , Ingrand Pierre , Christiaens Luc , Levesque Sébastien
Published: May 2018

Introduction

Specialized chest pain units appear to increase the proportion of patients with acute chest pain who are properly evaluated, but some of them remain doubtful.

Hypothesis

The aim of this study was to evaluate the survival and occurrence of cardiovascular events in patients without diagnosis at the end of management of chest pain with high‐sensitivity troponin (Tn) elevation.

Method

All consecutive patients who came to the cardiac emergency room of Poitiers University Hospital between January 1, 2014, and August 7, 2015, for chest pain and Tn elevation were included. The primary endpoint was the number of undiagnosed patients; secondary endpoints included survival and major adverse cardiac events.

Results

A total of 1001 patients (695 male; mean age, 68 ±16 years) who had chest pain and Tn elevation were included. Median follow‐up was 24.5 (IQR, 14.7–29.5) months. Forty‐seven (4.7%) patients remained without diagnosis. Compared with patients with diagnosis, these patients were younger (53.6 ±19.7 years; P < 0.0001) and had less hypertension (29.8%; P < 0.0001), diabetes (4.3%; P = 0.0016), and history of coronary artery disease (6.4%; P < 0.0001). No patients died or experienced MACE in 6‐month follow‐up. Survival curves showed the probability of survival was excellent, not only at 6 months, but also at 36 months (P = 0.0025).

Conclusions

Less than 5% of patients referred for chest pain and with high‐sensitivity Tn elevation remained without diagnosis after adapted care in the chest pain unit. Their 6‐month prognosis was excellent.
Optimal timing for cardioversion in patients with atrial fibrillation
Authors: Hellman Tapio , Kiviniemi Tuomas , Nuotio Ilpo , Biancari Fausto , Vasankari Tuija , Hartikainen Juha , Lehto Mika , Airaksinen K.E. ,   for the FinCV Investigators
Published: May 2018

Background

Electrical cardioversion (CV) is essential in rhythm management of atrial fibrillation (AF). However, optimal timing of CV remains unknown.

Hypothesis

Timing of CV in AF is associated with risk of adverse events.

Methods

We analyzed the effect of AF episode duration on safety and efficacy of electrical CV in a multicenter, multicohort study exploring 4356 CVs in 2530 patients on oral anticoagulation. The composite adverse outcome included unsuccessful CV, acute arrhythmic complications, thromboembolic events, mortality, and AF recurrence within 30‐day follow‐up.

Results

Study groups were stratified according to duration of index AF episode (<24 h, 24–48 h, 48 h–30d, and > 30d), consisting of 1767, 516, 632, and 1441 CVs, respectively. CVs were unsuccessful in 8.5% (<24 h), 5.4% (24–48 h), 11.1% (48 h–30d), and 13.9% (>30d), respectively (P < 0.01). Occurrence of thromboembolic events (0.1%), mortality (0.1%), and asystole >5 seconds (0.7%) within 30‐day follow‐up was infrequent and comparable in the study groups. AF recurrence within 30 days after initially successful CVs was 29.8% (<24 h), 26.5% (24–48 h), 37.3% (48 h–30d), and 30.3% (>30d), respectively (P < 0.01). Composite adverse outcome occurred in 1669 (38.4%) CVs, and index AF episode >48 hours was an independent predictor for the composite endpoint (OR: 1.49, 95% CI: 1.28–1.74, P < 0.01) in multivariate analysis.

Conclusions

Optimal timing of CV for AF showed a J‐shaped curve, with fewest adverse outcomes in patients with CV performed 24 to 48 hours after onset of AF. In patients with rhythm‐control strategy, delaying CV >48 hours is associated with increased risk for adverse outcomes.
Electrocardiographic diagnosis of atrial infarction in patients with acute inferior ST‐segment elevation myocardial infarction
Authors: Yıldız Suleyman Sezai , Keskin Kudret , Avsar Murat , Cetinkal Gokhan , Sigirci Serhat , Aksan Gokhan , Cetin Sukru , Okuyan Ertugrul , Kilickesmez Kadriye Orta
Published: May 2018

Background

Patients with atrial myocardial infarction (ATMI) have frequent cardiac and noncardiac complications. However, ATMI is uncommonly diagnosed because of its nonspecific ECG changes. Our objective was to analyze the ECG characteristics of ATMI in patients with inferior STEMI.

Hypothesis

Electrocardiographic P wave parameters can help in diagnosis of ATMI.

Methods

We evaluated 932 patients who underwent coronary angiography and recruited 39 patients with ATMI and 33 patients without ATMI with inferior STEMI for a retrospective study. Twelve‐lead ECGs were obtained to measure P‐wave parameters in diagnosis of ATMI. P‐wave parameters and PR‐segment displacement were compared in patients with and without ATMI.

Results

In inferior leads, PWD and PWDisp were significantly longer in the ATMI group than in the non‐ATMI group (limb lead II, 109.79 ±15.51 ms and 86.65 ±5.02 ms, respectively; P < 0.001; limb lead III, 108.31 ±12.51 ms and 85.27 ±7.47 ms, P < 0.001; aVF, 106.49 ±13.68 ms and 83.01 ±7.89 ms, P < 0.001; PWDisp, 41.67 ±10.72 ms and 25.18 ±5.17 ms, P < 0.001). By contrast, PWA was significantly lower in the ATMI group than in the non‐ATMI group (limb lead II, 0.96 ±0.18 mV and 1.39 ±0.22 mV, respectively; P < 0.001; limb lead III, 0.90 ±0.11 and 1.21 ±0.23, P < 0.001; aVF, 0.88 ±0.17 and 1.26 ±0.28, P < 0.001). PR‐segment displacement was found in 8 (20.5%) patients with ATMI. A PWD ≥95.5 ms in lead DII diagnosed ATMI with a higher sensitivity and specificity (90%, 94%) than did PWA or PWDisp.

Conclusions

This study suggests P‐wave parameters might be considered ECG findings in diagnosis of ATMI in patients with inferior STEMI.
A New Class of 1‐Aryl‐5,6‐dihydropyrrolo[2,1‐a]isoquinoline Derivatives as Reversers of P‐Glycoprotein‐Mediated Multidrug Resistance in Tumor Cells
Authors: Nevskaya Alisa A. , Matveeva Maria D. , Borisova Tatiana N. , Niso Mauro , Colabufo Nicola A. , Boccarelli Angelina , Purgatorio Rosa , de Candia Modesto , Cellamare Saverio , Voskressensky Leonid G. , Altomare Cosimo D.
Published: May 2018

A number of aza‐heterocyclic compounds, which share the 5,6‐dihydropyrrolo[2,1‐a]isoquinoline (DHPIQ) scaffold with members of the lamellarin alkaloid family, were synthesized and evaluated for their ability to reverse in vitro multidrug resistance in cancer cells through inhibition of P‐glycoprotein (P‐gp) and/or multidrug‐resistance‐associated protein 1. Most of the investigated DHPIQ compounds proved to be selective P‐gp modulators, and the most potent modulator, 8,9‐diethoxy‐1‐(3,4‐diethoxyphenyl)‐3‐(furan‐2‐yl)‐5,6‐dihydropyrrolo[2,1‐a]isoquinoline‐2‐carbaldehyde, attained sub‐micromolar inhibitory potency (IC50: 0.19 μm). Schiff bases prepared by the condensation of some 1‐aryl‐DHPIQ aldehydes with p‐aminophenol also proved to be of some interest, and one of them, 4‐((1‐(4‐fluorophenyl)‐5,6‐dihydro‐8,9‐dimethoxypyrrolo[2,1‐a]isoquinolin‐2‐yl)methyleneamino)phenol, had an IC50 value of 1.01 μm. In drug combination assays in multidrug‐resistant cells, some DHPIQ compounds, at nontoxic concentrations, significantly increased the cytotoxicity of doxorubicin in a concentration‐dependent manner. Studies of structure–activity relationships and investigation of the chemical stability of Schiff bases provided physicochemical information useful for molecular optimization of lamellarin‐like cytotoxic drugs active toward chemoresistant tumors as well as nontoxic reversers of P‐gp‐mediated multidrug resistance in tumor cells.
Design of Active Sites on Nickel in the Anode of Intermediate‐Temperature Solid Oxide Fuel Cells using Trace Amount of Platinum Oxides
Authors: Rednyk Andrii , Mori Toshiyuki , Yamamoto Shunya , Suzuki Akira , Yamamoto Yuta , Tanji Takayoshi , Isaka Noriko , Kúš Peter , Ito Shigeharu , Ye Fei
Published: May 2018

In recent years, the lowering of the operation temperature of solid oxide fuel cells (SOFCs) has attracted much attention owing to the trade‐off between the best performance and the life span of SOFCs. For this challenge, new active sites on the Ni surfaces in a Nickel–Yttria‐Stabilized Zirconia (Ni‐YSZ) cermet anode of SOFCs have been created by deposition of trace amounts of platinum oxide (PtOx) followed by an activation step of the anode at 1073 K in a hydrogen flow. The internal resistance (IR) free value (185 mA cm−2 at 0.8 V) observed for the single cell with an anode sputtered with a trace amount of PtOx (Pt content in anode: from 9 to 91 ppm) at 973 K is conspicuously higher than that of a similar single cell with a nonsputtered cermet anode (85 mA cm−2) at 0.8 V and 1073 K. Transmission electron microscopy microanalysis shows that the defect structure is formed on a partially oxidized Ni surface by active Pt species. Also, surface atomistic simulation on NiO (111) predicts the formation of Frenkel defect clusters with Pt cations, which partially cover the Ni surface. The formation of Frenkel defect clusters on the partially oxidized Ni surface (i.e., creation of new active sites for formation of water molecules) promotes the anode reaction, resulting in improvements in the anode performance of SOFC single cells at 973 K. Design of the aforementioned new active sites on Ni through sputtering of trace amounts of PtOx provides a great opportunity for “radical innovation” in the design of intermediate‐temperature SOFCs.
Occupancy modeling species–environment relationships with non‐ignorable survey designs
Authors: Irvine Kathryn M. , Rodhouse Thomas J. , Wright Wilson J. , Olsen Anthony R.
Published: May 2018

Statistical models supporting inferences about species occurrence patterns in relation to environmental gradients are fundamental to ecology and conservation biology. A common implicit assumption is that the sampling design is ignorable and does not need to be formally accounted for in analyses. The analyst assumes data are representative of the desired population and statistical modeling proceeds. However, if data sets from probability and non‐probability surveys are combined or unequal selection probabilities are used, the design may be non‐ignorable. We outline the use of pseudo‐maximum likelihood estimation for site‐occupancy models to account for such non‐ignorable survey designs. This estimation method accounts for the survey design by properly weighting the pseudo‐likelihood equation. In our empirical example, legacy and newer randomly selected locations were surveyed for bats to bridge a historic statewide effort with an ongoing nationwide program. We provide a worked example using bat acoustic detection/non‐detection data and show how analysts can diagnose whether their design is ignorable. Using simulations we assessed whether our approach is viable for modeling data sets composed of sites contributed outside of a probability design. Pseudo‐maximum likelihood estimates differed from the usual maximum likelihood occupancy estimates for some bat species. Using simulations we show the maximum likelihood estimator of species–environment relationships with non‐ignorable sampling designs was biased, whereas the pseudo‐likelihood estimator was design unbiased. However, in our simulation study the designs composed of a large proportion of legacy or non‐probability sites resulted in estimation issues for standard errors. These issues were likely a result of highly variable weights confounded by small sample sizes (5% or 10% sampling intensity and four revisits). Aggregating data sets from multiple sources logically supports larger sample sizes and potentially increases spatial extents for statistical inferences. Our results suggest that ignoring the mechanism for how locations were selected for data collection (e.g., the sampling design) could result in erroneous model‐based conclusions. Therefore, in order to ensure robust and defensible recommendations for evidence‐based conservation decision‐making, the survey design information in addition to the data themselves must be available for analysts. Details for constructing the weights used in estimation and code for implementation are provided.
The prevalence and impact of transient species in ecological communities
Authors: Snell Taylor Sara J. , Evans Brian S. , White Ethan P. , Hurlbert Allen H.
Published: May 2018

Transient species occur infrequently in a community over time and do not maintain viable local populations. Because transient species interact differently than non‐transients with their biotic and abiotic environment, it is important to characterize the prevalence of these species and how they impact our understanding of ecological systems. We quantified the prevalence and impact of transient species in communities using data on over 19,000 community time series spanning an array of ecosystems, taxonomic groups, and spatial scales. We found that transient species are a general feature of communities regardless of taxa or ecosystem. The proportion of these species decreases with increasing spatial scale leading to a need to control for scale in comparative work. Removing transient species from analyses influences the form of a suite of commonly studied ecological patterns including species–abundance distributions, species–energy relationships, species–area relationships, and temporal turnover. Careful consideration should be given to whether transient species are included in analyses depending on the theoretical and practical relevance of these species for the question being studied.
Cooperative Interactions in the Second Coordination Sphere of Pyridazine/Pyridine Containing Polyazaheterocyclic Iron(II) Complexes Favor Protonation
Authors: Hammoud Ahmad , Nshimyumuremyi Jean‐Boris , Bourotte Jérémie , Lucaccioni Fabio , Robeyns Koen , Dîrtu Marinela M. , Garcia Yann , Singleton Michael L.
Published: May 2018

The new pyridazine containing iron complexes, [N,N,N′,N′‐tetrakis(3‐pyridazylmethyl)propylenediamine]iron(II)(PF6)2 (1) and [N,N′‐bis(2‐pyridazylmethyl)‐N,N′‐bis(2‐pyridylmethyl)propylenediamine]iron(II) (PF6)2 (2) were synthesized and their reactivity towards protonation was compared to that of the analogous tetrapyridine complex [N,N,N′,N′‐tetrakis(2‐pyridylmethyl)propylenediamine]iron(II)(PF6)2 (3). The solution and solid‐state structures were confirmed by NMR and X‐ray crystallographic studies. For 1–3, the ligands bind in a hexadentate fashion giving similar octahedral structures with an N6 coordination environment. Across the series, the increasing number of pyridazines has only modest effects on the spectroscopic and electrochemical properties of the metal. Nevertheless, their reactivity towards protonation is drastically different. While 2 and 3 decompose in the presence of strong acids, 1 is able to be stably protonated as a result of cooperative second sphere interactions.