bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged river water pollution due to variable‐density flow and solute transport in the riverbed
Authors: Jin Guangqiu , Tang Hongwu , Li Ling , Barry D. A.
Published: February 2015

A laboratory experiment and numerical modeling were used to examine effects of density gradients on hyporheic flow and solute transport under the condition of a solute pulse input to a river with regular bed forms. Relatively low‐density gradients due to an initial salt pulse concentration of 1.55 kg m−3 applied in the experiment were found to modulate significantly the pore‐water flow and solute transport in the riverbed. Such density gradients increased downward flow and solute transport in the riverbed by factors up to 1.6. This resulted in a 12.2% increase in the total salt transfer from the water column to the riverbed over the salt pulse period. As the solute pulse passed, the effect of the density gradients reversed, slowing down the release of the solute back to the river water by a factor of 3.7. Numerical modeling indicated that these density effects intensified as salt concentrations in the water column increased. Simulations further showed that the density gradients might even lead to unstable flow and result in solute fingers in the bed of large bed forms. The slow release of solute from the bed back to the river led to a long tail of solute concentration in the river water. These findings have implications for assessment of impact of pollution events on river systems, in particular, long‐term effects on both the river water and riverbed due to the hyporheic exchange.
Iterative learning control for nonlinear dynamic systems with randomly varying trial lengths
Authors: Li Xuefang , Xu Jian‐Xin , Huang Deqing
Published: February 2015

In this paper, we introduce an iterative learning control (ILC) scheme based on an iteratively moving average operator for nonlinear dynamic systems with randomly varying trial lengths. By using the iteratively moving average operator, the proposed ILC algorithm overcomes the limitation of traditional ILC that all trial lengths must be identical. It is shown that for nonlinear affine and non‐affine systems, the proposed learning algorithm works effectively to nullify the tracking error. In the end, two illustrative examples are presented to demonstrate the performance and the effectiveness of the proposed ILC scheme for nonlinear dynamic systems. Copyright © 2015 John Wiley & Sons, Ltd.
Quantitative 3D X‐ray Imaging of Densification, Delamination and Fracture in a Micro‐Composite under Compression
Authors: Bø Fløystad Jostein , Skjønsfjell Eirik Torbjørn Bakken , Guizar‐Sicairos Manuel , Høydalsvik Kristin , He Jianying , Andreasen Jens Wenzel , Zhang Zhiliang , Breiby Dag Werner
Published: February 2015

Phase‐contrast three‐dimensional tomograms showing in unprecedented detail the mechanical response of a micro‐composite subjected to a mechanical compression test are reported. The X‐ray ptychography images reveal the deformation and fracture processes of a 10 μm diameter composite, consisting of a spherical polymer bead coated with a nominally 210 nm metal shell. The beginning delamination of the shell from the core can be directly observed at an engineering strain of a few percent. Pre‐existing defects are shown to dictate the deformation behavior of both core and shell. The strain state of the increasingly compressed polymer core is assessed quantitatively through the local densification at sub‐micron resolution, supported by finite element analysis. Nanoscale mechanics is of rapidly growing importance in materials science, biotechnology and medicine, and this study demonstrates the use of coherent X‐ray microscopy as a powerful tool for in situ studies of the mechanical properties of nanostructured devices, structures, and composites.
Molecular Heterojunctions of Oligo(phenylene ethynylene)s with Linear to Cruciform Framework
Authors: Wei Zhongming , Hansen Tim , Santella Marco , Wang Xintai , Parker Christian R. , Jiang Xingbin , Li Tao , Glyvradal Magni , Jennum Karsten , Glibstrup Emil , Bovet Nicolas , Wang Xiaowei , Hu Wenping , Solomon Gemma C. , Nielsen Mogens Brøndsted , Qiu Xiaohui , Bjørnholm Thomas , Nørgaard Kasper , Laursen Bo W.
Published: February 2015

Electrical transport properties of molecular junctions are fundamentally affected by the energy alignment between molecular frontier orbitals (highest occupied molecular orbital (HOMO) or lowest unoccupied molecular orbital (LUMO)) and Fermi level (or work function) of electrode metals. Dithiafulvene (DTF) is used as substituent group to the oligo(phenylene ethynylene) (OPE) molecular wires and different molecular structures based on OPE3 backbone (with linear to cruciform framework) are achieved, with viable molecular orbitals and HOMO–LUMO energy gaps. OPE3, OPE3–DTF, and OPE3–tetrathiafulvalene (TTF) can form good self‐assembled monolayers (SAMs) on Au substrates. Molecular heterojunctions based on these SAMs are investigated using conducting probe–atomic force microscopy with different tips (Ag, Au, and Pt) and Fermi levels. The calibrated conductance values follow the sequence OPE3–TTF > OPE3–DTF > OPE3 irrespective of the tip metal. Rectification properties (or diode behavior) are observed in case of the Ag tip for which the work function is furthest from the HOMO levels of the OPE3s. Quantum chemical calculations of the transmission qualitatively agree with the experimental data and reproduce the substituent effect of DTF. Zero‐bias conductance, and symmetric or asymmetric couplings to the electrodes are investigated. The results indicate that improved fidelity of molecular transport measurements may be achieved by systematic studies of homologues series of molecular wires applying several different metal electrodes.
Synthesis and Characterization of New Polyureas with Improved Thermal Stability from a Novel Ether Keto Diamine
Authors: Esfahanizadeh Mahshid , Sabbaghian Elahe , Mehdipour‐Ataei Shahram , Jalilian Seyedmehrdad , Babanzadeh Samal
Published: February 2015

A novel diamine monomer was prepared in three steps: first, a nucleophilic substitution reaction between hydroquinone and 1‐flouro‐4‐nitrobenzene afforded a nitro compound. Second, the nitro group of this compound was converted to an amino group via reduction in the presence of hydrazine hydrate. In the last step, the reaction of this compound with 4,4'‐diflouro benzophenone led to the synthesis of a novel ether keto diamine. Characterization of all materials was carried out by conventional spectroscopic methods and elemental analysis. A series of new polyureas was prepared via the polymerization reaction of the synthesized diamine with three commercially available diisocyanates including 4,4'‐diphenylmethan diisocyanate, toluene‐2,4‐diisocyanate, and isophoronediisocyanate in N‐methyl‐2‐pyrrolidone. The resulted polyureas were characterized by infrared spectroscopy and elemental analysis. The inherent viscosities of these polyureas ranged from 0.59 to 0.62 dL/g measured at a concentration of 0.5 g/dL. The resulting polyureas were soluble in dipolar aprotic solvents. The thermal properties of the polymers were investigated by differential scanning calorimetry and thermogravimetric analysis. The results indicated that their glass transition temperature values were between 171 and 198°C and at the 10% weight loss of polymers, glass transition temperature was about 325–368°C showing improved thermal stability in comparison with common polyureas. Thermal stability features of the polyurea were also confirmed by means of the pyrolysis‐gas chromatography/mass spectrometry method.
An Efficient and Green Synthesis of 1‐Indanone and 1‐Tetralone via Intramolecular Friedel–Crafts Acylation Reaction
Authors: Tran Phuong Hoang , Huynh Vy Hieu , Hansen Poul Erik , Chau Duy‐Khiem Nguyen , Le Thach Ngoc
Published: February 2015

Metal‐triflate‐catalyzed intramolecular Friedel–Crafts acylation of 3‐arylpropanoic and 4‐arylbutanoic acids in triflate‐anion ionic liquids under monomodal microwave irradiation is reported. The environmentally benign synthetic procedure allows the formation of cyclic ketones in good yields within a short reaction time. The catalytic metal triflate in triflate‐anion ionic liquids can be easily recovered and reused several times without significant loss of the catalytic performance.
Cu3(hexaiminotriphenylene)2: An Electrically Conductive 2D Metal–Organic Framework for Chemiresistive Sensing
Authors: Campbell Michael G. , Sheberla Dennis , Liu Sophie F. , Swager Timothy M. , Dincă Mircea
Published: February 2015

The utility of metal–organic frameworks (MOFs) as functional materials in electronic devices has been limited to date by a lack of MOFs that display high electrical conductivity. Here, we report the synthesis of a new electrically conductive 2D MOF, Cu3(HITP)2 (HITP=2,3,6,7,10,11‐hexaiminotriphenylene), which displays a bulk conductivity of 0.2 S cm−1 (pellet, two‐point‐probe). Devices synthesized by simple drop casting of Cu3(HITP)2 dispersions function as reversible chemiresistive sensors, capable of detecting sub‐ppm levels of ammonia vapor. Comparison with the isostructural 2D MOF Ni3(HITP)2 shows that the copper sites are critical for ammonia sensing, indicating that rational design/synthesis can be used to tune the functional properties of conductive MOFs.
Industrial melt index prediction with the ensemble anti‐outlier just‐in‐time Gaussian process regression modeling method
Authors: Liu Yi , Gao Zengliang
Published: February 2015

Several data‐driven soft sensors have been applied for online quality prediction in polymerization processes. However, industrial data samples often follow a non‐Gaussian distribution and contain some outliers. Additionally, a single model is insufficient to capture all of the characteristics in multiple grades. In this study, the support vector clustering (SVC)‐based outlier detection method was first used to better handle the nonlinearity and non‐Gaussianity in data samples. Then, SVC was integrated into the just‐in‐time Gaussian process regression (JGPR) modeling method to enhance the prediction reliability. A similar data set with fewer outliers was constructed to build a more reliable local SVC–JGPR prediction model. Moreover, an ensemble strategy was proposed to combine several local SVC–JGPR models with the prediction uncertainty. Finally, the historical data set was updated repetitively in a reasonable way. The prediction results in the industrial polymerization process show the superiority of the proposed method in terms of prediction accuracy and reliability. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41958.
Phosphor settling induced mechanical degradation of silicone/phosphor composite in light emitting diode packages
Authors: Chen Xing , Wang Simin , Chen Mingxiang , Liu Sheng
Published: February 2015

Silicone/phosphor composite is a functional material used in light emitting diode (LED) packages. In this article, effect of phosphor settling on mechanical properties and microstructure of phosphor/silicone composite is investigated experimentally and numerically. Test samples of silicones with various degrees of phosphor settling were prepared and uniaxial tensile tests were conducted. The results indicate that, for specific volume fraction of phosphor, phosphor sedimentation tends to reduce the strength and elongation of overall composite. And with increasing degree of sedimentation, the weakening effect becomes more significant. The fractographs of the test samples indicate that cracks initiate around the bottom area where phosphor particles settle. Numerical investigations, which were conducted by random unit cell model with graded particle distribution, demonstrate that strain localization and stress concentration are significant where phosphor particles concentrate. It can be concluded that, to reduce mechanical degradation, phosphor sedimentation should be minimized in silicone/phosphor composite for LED packages. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42006.
Synthesis, Biological Evaluation and Molecular Docking of Calix[4]arene‐Based β‐Diketo Derivatives as HIV‐1 Integrase Inhibitors
Authors: Luo Zaigang , Zhao Yu , Ma Chao , Li Zhipeng , Xu Xuemei , Hu Liming , Huang Nianyu , He Hongqiu
Published: February 2015

In this publication, we design and report the synthesis of calix[4]arene‐based β‐diketo derivatives as novel HIV‐1 integrase (IN) inhibitors. The target compounds were obtained using Claisen condensation, and their structures were characterized by NMR and ESI‐MS. Preliminary bioassays showed that calix[4]arene‐based β‐diketo derivatives inhibit strand transfer (ST) with IC50 values between 5.9 and 21.2 µM. Docking studies revealed the predominant binding modes that were distinct from the binding modes of raltegravir, which suggests a novel binding region in the IN active site. Moreover, these compounds are predicted not to interact with some of the key amino acids (GLN148 and ASN155) implicated in viral resistance. Therefore, this series of compounds can further be investigated for a possible chemotype to circumvent resistance to clinical HIV‐1 IN inhibitors.
Randomized, Double‐Blind, Dose‐Escalation Trial of Triptorelin for Ovary Protection in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Brunner Hermine I. , Silva Clovis A. , Reiff Andreas , Higgins Gloria C. , Imundo Lisa , Williams Calvin B. , Wallace Carol A. , Aikawa Nadia E. , Nelson Shannen , Klein‐Gitelman Marisa S. , Rose Susan R.
Published: February 2015

Objective

To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood‐onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin.

Methods

In this randomized, double‐blind, placebo‐controlled, dose‐escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight‐adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin‐releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle‐stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment.

Results

Treatment with triptorelin at a weight‐adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient‐months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5).

Conclusion

High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood‐onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued.
A non‐default rate regression model for credit scoring
Authors: Barriga Gladys D. C. , Cancho Vicente G. , Louzada Francisco
Published: February 2015

In this paper, we propose a new non‐default rate survival model. Our approach enables different underlying activation mechanisms which lead to the event of interest. The number of competing causes, which may be responsible for the occurrence of the event of interest, is assumed to follow a geometric distribution, while the time to event is assumed to follow an inverse Weibull distribution. An advantage of our approach is to accommodate all activation mechanisms based on order statistics. We explore the use of maximum likelihood estimation procedure. Simulation studies are performed and experimental results are illustrated based on a real Brazilian bank personal loan portfolio data. Copyright © 2015 John Wiley & Sons, Ltd.
Nitrate reductase, nitrite reductase, glutamine synthetase, and glutamate synthase expression and activity in response to different nitrogen sources in nitrogen‐starved wheat seedlings
Authors: Balotf Sadegh , Kavoosi Gholamreza , Kholdebarin Bahman
Published: February 2015

The objective of this study was to examine the expression and activity of nitrate reductase (NR, EC 1.7.1.1), nitrite reductase (NiR, EC 1.7.2.2), glutamine synthetase (GS, EC 6.3.1.2), and glutamate synthase (GOGAT, EC 1.4.7.1) in response to potassium nitrate, ammonium chloride, and ammonium nitrate in nitrogen‐starved wheat seedlings. Plants were grown in standard nutrient solution for 17 days and then subjected to nitrogen starvation for 7 days. The starved plants were supplied with potassium nitrate ammonium nitrate and ammonium chloride (50 mM) for 4 days and the leaves were harvested. The relative expression of NR, NiR, GS, and GOGAT as well as the enzyme activities were investigated. Nitrogen starvation caused a significant decrease both in transcript levels and in NR, NiR, GS, and GOGAT activities. Potassium nitrate and ammonium nitrate treatments restored NR, NiR, GS, and GOGAT expressions and activities. Ammonium chloride increased only the expressions and activities of GS and GOGAT in a dose‐dependent manner. The results of our study highlight the differential effects between the type and the amount of nitrogen salts on NR, NiR, GS, and GOGAT activities in wheat seedlings while potassium nitrate being more effective.
Age Differences in Risk: Perceptions, Intentions and Domains
Authors: Bonem Emily M. , Ellsworth Phoebe C. , Gonzalez Richard
Published: February 2015

Although it is commonly assumed that older people are more cautious and risk averse than their younger counterparts, the research on age differences in risk taking is mixed. While some research has found that older adults are less risk seeking, other research has found the opposite or no differences. One explanation is that age differences vary across risk domains. In two studies, we surveyed three adult age groups ranging in age from 18 to 83 on their risk perceptions and intentions of risky behaviors across several domains. Our studies showed that compared with young adults, older adults tend to see more risk in behaviors in health and ethical domains but less risk in behaviors from the social domain. A similar pattern occurred for participants' intentions of engaging in the risky behaviors. Older adults rated risky behaviors from health and ethical domains as less enjoyable and less likely to produce gains than young adults, whereas they rated risky behaviors from the social domain as more enjoyable, less unpleasant, and less likely to produce losses than young adults. These results suggest that age differences in risk preferences may vary across domains and may result from differing motivations. Copyright © 2015 John Wiley & Sons, Ltd.
Do Bettors Correctly Perceive Odds? Three Studies of How Bettors Interpret Betting Odds as Probabilistic Information
Authors: Andersson Patric , Nilsson Håkan
Published: February 2015

This paper reports on three studies investigating how accurately bettors (=people who regularly bet on sports events) interpret the probabilistic information implied by betting odds. All studies were based on data collected by web surveys prompting a total of 186 experienced bettors to convert sets of representative odds into frequency judgments. Bayesian statistical methods were used to analyze the data. From the results, the following conclusions were made: (i) On the whole, the bettors produced well‐calibrated judgments, indicating that they have realistic perceptions of odds. (ii) Bettors were unable to consciously adjust judgments for different margins. (iii) Although their interval judgments often covered the estimates implied by the odds, the bettors tended to overestimate the variation of expected profitable bets between months. The results are consistent with prior research showing that people tend to make accurate probability judgments when faced with tasks characterized by constant and clear feedback. Copyright © 2015 John Wiley & Sons, Ltd.
Assessing protein conformational sampling and structural stability via de novo design and molecular dynamics simulations
Authors: Cunha Keila C. , Rusu Victor H. , Viana Isabelle F. T. , Marques Ernesto T. A. , Dhalia Rafael , Lins Roberto D.
Published: February 2015

Molecular dynamics and de novo techniques, associated to quality parameter sets, have excelled at determining the structure of small proteins with high accuracy. To achieve a detailed description of protein conformations, these methods must critically assess the thermodynamic features of the molecular ensembles. Here, a comparison of the conformational ensemble generated by molecular dynamics and de novo techniques were carried out for six Top7‐based proteins carrying gp41 HIV‐1 epitopes. The native Top7, a highly stable computationally designed protein, was used as benchmark. Structural stability, flexibility, and secondary structure content were assessed. The consistency of the latter was compared to experimental circular dichroism spectra for all proteins. While both methods are capable to identify the stable from unstable chimeric proteins, the sampled conformational space and flexibility differ significantly in both methods. Molecular dynamics simulations seem to better describe secondary structure content and identify regions responsible for conformational instability. The de novo method, as implemented in Rosetta—a prime tool for protein design, overestimates secondary structure content. On the other hand, its empirical energy function is capable to predict the threshold for protein stability. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 351–361, 2015.
Selective solid‐phase extraction of artificial chemicals from milk samples using multiple‐template surface molecularly imprinted polymers
Authors: Zhang Jing , Ni Yan‐li , Wang Ling‐ling , Ma Jin‐qin , Zhang Zhi‐qi
Published: February 2015

A novel multiple‐template surface molecularly imprinted polymer (MTMIP) was synthesized using ofloxacin and 17β‐estradiol as templates and modified monodispersed poly(glycidylmethacrylate‐co‐ethylene dimethacrylate) (PGMA/EDMA) beads as the support material. Static adsorption, solid‐phase extraction and high‐performance liquid chromatography were performed to investigate the adsorption properties and selective recognition characteristics of the polymer templates and their structural analogs. The maximum binding capacities of ofloxacin and 17β‐estradiol on the MTMIP were 9.0 and 6.6 mg/g, respectively. Compared with the corresponding nonimprinted polymer, the MTMIP exhibited a much higher adsorption performance and selectivity toward three quinolones and three estrogens, which are common drug residues in food. The MTMIP served as a simple and effective pretreatment method and could be successfully applied to the simultaneous analysis of multiple target components in complex samples. Furthermore, the MTMIP may find useful applications as a solid‐phase absorbent in the simultaneous determination of trace quinolones and estrogens in milk samples, as the recoveries were in the range 77.6–98.0%. Copyright © 2015 John Wiley & Sons, Ltd.
Purification and characterization of organic solvent stable serine alkaline protease from newly isolated Bacillus circulans M34
Authors: Sari Esma , Loğoğlu Elif , Öktemer Atilla
Published: February 2015

A protease from newly isolated Bacillus circulans M34 was purified by Q‐Sepharose anion exchange chromatography and Sepharose–bacitracin affinity chromatography followed by (NH4)2SO4 precipitation. The molecular mass of the purified enzyme was determined using SDS–PAGE. The optimum pH and temperature for protease activity were 11 and 50°C, respectively. The effect of various metal ions on protease activity was investigated. Alkaline protease from Bacillus circulans M34 wase activated by Zn2+, Cu2+ and Co2+ up to 31%. The purified protease was found to be stable in the organic solvents, surfactants and oxidizing agent. The substrate specificity of purified protease was investigated towards different substrates. The protease was almost completely inhibited by the serine protease inhibitor phenylmethanesulfonyl fluoride. The kinetic parameters of the purified protease, maximum rate (Vmax) and Michaelis constant (Km), were determined using a Lineweaver–Burk plot. Copyright © 2015 John Wiley & Sons, Ltd.
Simultaneous quantification of curdione, furanodiene and germacrone in rabbit plasma using liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study
Authors: Wang Baolian , Yang Shuang , Sheng Li , Li Yan
Published: February 2015

A simple, rapid and sensitive method was developed for the simultaneous quantification of curdione, furanodiene and germacrone in rabbit plasma using a LC‐MS/MS analysis. The plasma sample preparation was a simple deproteinization by the addition of 3 vols of acetonitrile followed by centrifugation. The analytes and internal standard (IS) costunolide were separated on a Zorbax SB‐C18 column (3.5 µm, 2.1 × 100 mm) with mobile phase of methanol–water (90:10, v/v) containing 0.1% formic acid at a flow rate of 0.3 mL/min with an operating temperature of 25°C. Detection was carried out by atmospheric pressure chemical ionization in positive ion selected reaction monitoring mode. Linear detection responses were obtained for the three test compounds ranging from 5 to 5000 ng/mL and the lower limits of quantitation were 5‐10ng/mL. The intra‐ and inter‐day precisions (relative standard deviations) were within 9.4% for all analytes, while the deviation of assay accuracies was within ±10.0%. The average recoveries of analytes were >80.0%. All analytes were proved to be stable during all sample storage, preparation and analytical procedures. The method was successfully applied to the pharmacokinetic study of the three compounds after vaginal drug delivery of Baofukang suppository to rabbit. Copyright © 2015 John Wiley & Sons, Ltd.
Simultaneous quantitative determination of 20 active components in the traditional Chinese medicine formula Zhi‐Zi‐Da‐Huang decoction by liquid chromatography coupled with mass spectrometry: application to study the chemical composition variations in different combinations
Authors: Tang Zheng , Yin Ran , Bi Kaishun , Zhu Heyun , Han Fei , Chen Kelin , Wang Fenrong
Published: February 2015

Zhi‐Zi‐Da‐Huang decoction (ZZDHD), a classical traditional Chinese medicine (TCM) prescription composed of four herbal medicines, has been widely used in treating various hepatobiliary disorders for a long time. The objective of this study was to develop a sensitive and efficient liquid chromatography coupled with mass spectrometry (LC‐MS) method for quantitative determination of 20 active constituents, including three iridoid glycosides, 11 flavonoids, three anthraquinones and three tannins in ZZDHD. Separation was achieved on a phenomenex kinetex C18column (150 × 4.6 mm, 2.6 µm) using gradient elution with a mobile phase consisting of acetonitrile and 0.1% formic acid in water. Detection was performed with electrospray ionization source in the negative ionization and selected ion monitoring mode. The established method was validated by determining the linearity (r2≥ 0.9983), limit of quantification (0.16–300 ng/mL), precision (RSD ≤ 4.6%), average recovery (96.0–105.6%), repeatability (RSD ≤ 3.2%) and stability (RSD ≤ 4.5%). Then, the method was successfully applied to investigate the chemical composition variations owing to the interaction between the four component herbs of ZZDHD during the extraction process. It was found that different combinations of the herbs affect the extraction efficiency of chemical constituents in different ways. The validated LC‐MS method provides a meaningful basis for quality control and further research on ZZDHD. Copyright © 2015 John Wiley & Sons, Ltd.
Comparsion of an immunochromatographic strip with ELISA for simultaneous detection of thiamphenicol, florfenicol and chloramphenicol in food samples
Authors: Guo Lingling , Song Shanshan , Liu Liqiang , Peng Juan , Kuang Hua , Xu Chuanlai
Published: February 2015

Rapid and sensitive indirect competitive enzyme‐linked immunosorbent assays (ic‐ELISA) and gold nanoparticle immunochromatographic strip tests were developed to detect thiamphenicol (TAP), florfenicol (FF) and chloramphenicol (CAP) in milk and honey samples. The generic monoclonal antibody for TAP, FF and CAP was prepared based on a hapten [D‐threo‐1‐(4‐aminophenyl)‐2‐ dichloroacetylamino‐1,3‐propanediol], and the haptenwas linked to a carrier protein using the diazotization method. After the optimization of several parameters (coating, pH, sodium chloride content and methanol content), the ic‐ELISA was established. The quantitative working range for TAP was 0.11–1.36 ng/mL, with an IC50 of 0.39 ng/mL. The optimized ELISA showed cross‐reactivity to CAP (300%) and FF (15.6%), with IC50 values of 0.13 and 2.5 ng/mL, respectively. The analytical recovery of TAP, FF and CAP in milk and honey samples in the ic‐ELISA ranged from 81.2 to 112.9%. Based on this monoclonal antibody, a rapid and sensitive immunochromatographic test strip was also developed. This strip had a detection limit of 1 ng/mL for TAP, FF and CAP in milk and honey samples. Moreover, the test was completed within 10 min. Our results showed that the proposed ic‐ELISA and immunochromatographic test strip method are highly useful screening tools for TAP, FF and CAP detection in milk and honey samples. Copyright © 2015 John Wiley & Sons, Ltd.
Dinitriles Bearing AIE‐Active Moieties: Synthesis, E/Z Isomerization, and Fluorescence Properties
Authors: Tasso Thiago Teixeira , Furuyama Taniyuki , Kobayashi Nagao
Published: February 2015

Dinitriles bearing aggregation‐induced emission (AIE)‐active moieties [tetraphenylethylene (TPE) or diphenylphenanthrene (DPP)] were prepared. Compounds 4 (TPE‐linked) and 8 (DPP‐linked) showed considerably redshifted emission resulting from their large Stokes shifts and also strong fluorescence in the aggregated and solid states. Pure E and Z stereoisomers of both dinitriles were easily separated, and their isomerization equilibria and fluorescence properties were investigated. In addition to their pronounced AIEE behavior, 4 and 8 also showed various reversible chromic responses to external stimuli, namely, solvato‐, piezo‐, vapo‐, and thermochromism, which make them potential candidates for smart materials.
Copper‐Catalyzed Asymmetric Three‐Component Borylstannation: Enantioselective Formation of CSn Bond
Authors: Jia Tao , Cao Peng , Wang Ding , Lou Yazhou , Liao Jian
Published: February 2015

In summary, a first copper‐catalyzed synthesis of α‐aryl‐β‐borylstannane compounds was accomplished through three‐component borylstannation of aryl‐substituted alkenes. In the exploration of an asymmetric variant, chiral sulfinylphosphine ligands proved advantageous in controlling stereochemistry of BCu addition and in promoting transmetalation of enantioenriched alkylCu species. The stereochemical outcome supported a sequential syn‐borylcupration and configuration‐retentive transmetalation mechanism. Moreover, α‐chiral β‐borylstannanes were easily transformed into a diverse array of secondary alkylstannanes and triarylethane with high enantiomeric purity. The applications of chiral sulfinylphosphine ligands to other tandem CuB addition reactions are currently under investigation in our group.
Bedside clinical signs associated with impending death in patients with advanced cancer: Preliminary findings of a prospective, longitudinal cohort study
Authors: Hui David , dos Santos Renata , Chisholm Gary , Bansal Swati , Souza Crovador Camila , Bruera Eduardo
Published: February 2015

BACKGROUND

Five highly specific physical signs associated with death within 3 days among cancer patients were recently reported that may aid in the diagnosis of impending death. In this study, the frequency and onset of another 52 bedside physical signs and their diagnostic performance for impending death were examined.

METHODS

Three hundred fifty‐seven consecutive patients with advanced cancer who had been admitted to acute palliative care units at 2 tertiary care cancer centers were enrolled. Fifty‐two physical signs were systematically documented every 12 hours from admission to death or discharge. The frequency and median time of onset of each sign from death backwards were examined, and the likelihood ratios (LRs) associated with death within 3 days were calculated.

RESULTS

Two hundred three of the 357 patients (57%) died at the end of the admission. Eight physical signs that were highly diagnostic of impending death were identified. These signs occurred in 5% to 78% of the patients within the last 3 days of life, had a late onset, and had a high specificity (>95%) and a high positive LR for death within 3 days. They included nonreactive pupils (positive LR, 16.7; 95% confidence interval [CI], 14.9‐18.6), a decreased response to verbal stimuli (positive LR, 8.3; 95% CI, 7.7‐9), a decreased response to visual stimuli (positive LR, 6.7; 95% CI, 6.3‐7.1), an inability to close eyelids (positive LR, 13.6; 95% CI, 11.7‐15.5), drooping of the nasolabial fold (positive LR, 8.3; 95% CI, 7.7‐8.9), hyperextension of the neck (positive LR, 7.3; 95% CI, 6.7‐8), grunting of vocal cords (positive LR, 11.8; 95% CI, 10.3‐13.4), and upper gastrointestinal bleeding (positive LR, 10.3; 95% CI, 9.5‐11.1).

CONCLUSIONS

Eight highly specific physical signs associated with death within 3 days among cancer patients were identified. These signs may inform the diagnosis of impending death. Cancer 2015;121:960–967. © 2014 American Cancer Society.
Colocalization of allatotropin and tachykinin‐related peptides with classical transmitters in physiologically distinct subtypes of olfactory local interneurons in the cockroach (Periplaneta americana)
Authors: Fusca Debora , Schachtner Joachim , Kloppenburg Peter
Published: February 2015

In the insect antennal lobe different types of local interneurons mediate complex excitatory and inhibitory interactions between the glomerular pathways to structure the spatiotemporal representation of odors. Mass spectrometric and immunohistochemical studies have shown that in local interneurons classical neurotransmitters are likely to colocalize with a variety of substances that can potentially act as cotransmitters or neuromodulators. In the antennal lobe of the cockroach Periplaneta americana, gamma‐aminobutyric acid (GABA) has been identified as the potential inhibitory transmitter of spiking type I local interneurons, whereas acetylcholine is most likely the excitatory transmitter of nonspiking type IIa1 local interneurons. This study used whole‐cell patch clamp recordings combined with single‐cell labeling and immunohistochemistry to test if the GABAergic type I local interneurons and the cholinergic type IIa1 local interneurons express allatotropin and tachykinin‐related neuropeptides (TKRPs). These are two of the most abundant types of peptides in the insect antennal lobe. GABA‐like and choline acetyltransferase (ChAT)‐like immunoreactivity were used as markers for GABAergic and cholinergic neurons, respectively. About 50% of the GABA‐like immunoreactive (‐lir) spiking type I local interneurons were allatotropin‐lir, and ∼40% of these neurons were TKRP‐lir. About 20% of nonspiking ChAT‐lir type IIa1 local interneurons were TKRP‐lir. Our results suggest that in subpopulations of GABAergic and cholinergic local interneurons, allatotropin and TKRPs might act as cotransmitters or neuromodulators. To unequivocally assign neurotransmitters, cotransmitters, and neuromodulators to identified classes of antennal lobe neurons is an important step to deepen our understanding of information processing in the insect olfactory system. J. Comp. Neurol. 523:1569–1586, 2015. © 2015 Wiley Periodicals, Inc.
Rational use of medicines in older adults: Can we do better during clinical development?
Authors: Saeed MA , Vlasakakis G , Della Pasqua O
Published: February 2015

There is an evidence gap to ensuring safe/effective use of medicines in older adults. Generating clinical data in these patients poses ethical and operational challenges, yielding results that may not be generalizable to the overall population. Modeling and simulation (M&S) is proposed as a basis for assessing the impact of age‐related changes and their clinical implications. M&S can be used in conjunction with bridging and extrapolation to ensure the selection of appropriate dose(s)/regimen(s) in this population.
Innovative Clinical Trials: The LUNG‐MAP Study
Authors: Steuer CE , Papadimitrakopoulou V , Herbst RS , Redman MW , Hirsch FR , Mack PC , Ramalingam SS , Gandara DR
Published: February 2015

Although the proportion of patients with squamous cell carcinoma of the lung has declined over the last two decades, the disease is still fatal for tens of thousands of patients each year. The treatment of non–small cell lung cancer has advanced rapidly over the past decade, providing novel, targeted therapeutic options to patients, but has mostly been limited to the adenocarcinoma histology. Efforts are currently underway to bring squamous cell carcinoma of the lung into this new era of targeted therapy. This article reviews the rationale and trial design for the “LUNG‐MAP: S1400 Phase II/III Biomarker‐Driven Master Protocol for Second Line Therapy of Squamous Cell Lung Cancer” study. This multi‐institutional, multi‐cooperative group trial aims to individualize treatment for patients with metastatic squamous cell carcinoma to one of five arms based on the genomic profile of the tumor. The goal of this clinical trial is to rapidly identify new active drugs and bring them as soon as possible through a registration process for patients with squamous cell lung cancer by utilizing a novel trial design and involving all key stakeholders in drug development in a national effort. This could serve as a paradigm for drug development for malignancies with wide molecular heterogeneity.
Fractional‐order mutual inductance: analysis and design
Authors: Soltan Ahmed , Radwan Ahmed G. , Soliman Ahmed M.
Published: February 2015

This paper introduces for the first time the generalized concept of the mutual inductance in the fractional‐order domain where the symmetrical and unsymmetrical behaviors of the fractional‐order mutual inductance are studied. To use the fractional mutual inductance in circuit design and simulation, an equivalent circuit is presented with its different conditions of operation. Also, simulations for the impedance matrix parameters of the fractional mutual inductance equivalent circuit using Advanced Design System and MATLAB are illustrated. The Advanced Design System and MATLAB simulations of the double‐tuned filter based on the fractional mutual inductance are discussed. A great matching between the numerical analysis and the circuit simulation appears, which confirms the reliability of the concept of the fractional mutual inductance. Also, the analysis of the impedance matching using the fractional‐order mutual inductance is introduced. Copyright © 2015 John Wiley & Sons, Ltd.
Segmentation and tracking of stem cells in time lapse microscopy to quantify dynamic behavioral changes during spheroid formation
Authors: Jiang Ching‐Fen , Hsu Shan‐hui , Tsai Ka‐Pei , Tsai Ming‐Hong
Published: February 2015

Dynamic behavior of stem cells during in vitro development is diverse. Previous cell tracking studies have focused more on cell proliferation than on cell aggregation. However, the enhancement of cell proliferation in association with cell aggregation has been reported. In a previous study, we also demonstrated that the aggregation of adult human mesenchymal stem cells to form three‐dimensional (3D) cellular spheroids helped maintain the expression of stemness marker genes in the cells. However, the dynamic behavioral changes triggered by spheroid formation remain to be investigated. A scheme of image processing techniques is proposed to meet this need. A hybrid‐thresholding technique was first developed for efficient segmentation of cell clusters, after which a cell tracking method based on pair‐matching with topological constraints was designed. Two morphological indices were derived to track the timing of 3D spheroid formation during the cellular aggregation process. Five cell motility indices measured from single cells and 3D spheroids were then compared. After confirmation of more than 90% correspondence between the results obtained by manual tracking and the proposed methods, an analysis of cellular behavior reveals a significant increase in motility in association with spheroid formation, consistent with a previous report that used a gene expression approach. This study proposed a systematic image analysis method to quantify the dynamic behavior of stem cells for stemness evaluation during cell culturing in vitro. Results demonstrated the validity of the developed platform in investigation of the dynamic behavior of cell aggregation in stem cell cultures in vitro. © 2015 International Society for Advancement of Cytometry
Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study‐Heart Failure (ARTS‐HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease
Authors: Pitt Bertram , Anker Stefan D. , Böhm Michael , Gheorghiade Mihai , Køber Lars , Krum Henry , Maggioni Aldo P. , Ponikowski Piotr , Voors Adriaan A. , Zannad Faiez , Nowack Christina , Kim So‐Young , Pieper Alexander , Kimmeskamp‐Kirschbaum Nina , Filippatos Gerasimos
Published: February 2015

Aims

To investigate the safety and potential efficacy of the novel non‐steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction.

Methods and results

The MinerAlocorticoid Receptor antagonist Tolerability Study‐Heart Failure (ARTS‐HF; NCT01807221) is a multicentre, randomized, double‐blind, active‐comparator‐controlled, six‐parallel‐group, phase 2b dose‐finding study. In total, 1060 patients with HFrEF and concomitant type 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5–20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days). The primary objective is to investigate the safety and potential efficacy (measured as the percentage of individuals with a decrease in plasma N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP] of more than 30% relative to baseline at day 90 ± 2) of different oral doses of finerenone compared with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health‐related quality of life from baseline.

Conclusions

ARTS‐HF is the first phase 2b clinical trial to investigate the effects of finerenone on plasma NT‐proBNP in a high‐risk population of patients who have worsening chronic HF with type 2 diabetes mellitus and/or CKD presenting at the emergency department.
Alkynyl‐Functionalized Imidazolium for “Click” Dendrimer Functionalisation and Palladium Nanoparticle Stabilization
Authors: Deraedt Christophe , d'Halluin Martin , Lesturgez Stephanie , Salmon Lionel , Goglio Graziella , Ruiz Jaime , Astruc Didier
Published: February 2015

Functionalization of imidazolium salts (IMSs) that allow easy derivation of molecular or solid supports are called for in various applications. Here, the synthesis of an alkyne‐containing IMS can be achieved in three steps from 2,4,6‐trimethylaniline, and this IMS can be further successfully functionalized by using either Sonogashira or a “click” CuAAC reaction that was applied to dendritic IMS synthesis giving high yields. Applications are illustrated for Pd nanoparticle stabilization by the IMS dendrimer for Suzuki–Miyaura catalysis.
Al3+‐Ion‐Triggered Conformational Isomerization of a Rhodamine B Derivative Evidenced by a Fluorescence Signal – A Crystallographic Proof
Authors: Sen Buddhadeb , Pal Siddhartha , Banerjee Samya , Lohar Somenath , Chattopadhyay Pabitra
Published: February 2015

A newly designed rhodamine B anisaldehyde hydrazone exhibits Al3+‐ion‐induced cis (L) to trans (L′) conformational isomerization with respect to the xanthene moiety through a rotation about a N–N bond; the isomerization is indicated by a detectable naked‐eye color change and a turn‐on red fluorescence in 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (HEPES) buffer (EtOH/Water 1:9 v/v; pH 7.4) at 25 °C. In support of this observation, detailed spectroscopic and physicochemical studies along with density function theory (DFT) calculations have been performed. This cis‐to‐trans conformational isomerization is due to Al3+ ion coordination, which induces this visual color change and the turn‐on fluorescence response. To strengthen our knowledge of the conformational isomerization, detailed structural characterizations of the cis and trans isomers in the solid state were performed by single‐crystal X‐ray diffraction. To the best of our knowledge, this is the first structural report of both cis and trans conformational isomers for this family of compounds. Moreover, this noncytotoxic probe could be used to image the accumulation of Al3+ ions in HeLa and MCF‐7 cell lines.
Antimicrobial and Antitumor Activity of Enantiopure Pybox–Osmium Complexes
Authors: Menéndez‐Pedregal Estefanía , Manteca Ángel , Sánchez Jesús , Díez J. , Gamasa M. Pilar , Lastra Elena
Published: February 2015

The antiproliferative activities of enantiopure (S,S)‐iPr‐pybox osmium(II) complexes {(S,S)‐iPr‐pybox = 2,6‐bis[4′(S)‐isopropyloxazolin‐2′‐yl]pyridine} against microbes and tumor cell lines (HeLa and HT29) as well as their interactions with plasmidic DNA have been studied. All of the analyzed compounds interacted in vitro with plasmidic DNA. They also interacted in vivo with microbes and tumor cell lines, as demonstrated by their interference with microbial growth and induction of apoptosis in HeLa cells. In particular, an IC50 value of 2.7 ± 0.3 μM has been found for trans‐[OsCl2{(S,S)‐iPr‐pybox}(1‐PhCH2‐PTA)][Br] (PTA = 1,3,5‐triaza‐7‐phosphatricyclo[3.3.1.13,7]decane). All of the water‐soluble complexes used in these studies have been synthesized in high yields and were fully characterized.
A Tuned Bicyclic Proazaphosphatrane for Catalytically Enhanced N‐Arylation Reactions with Aryl Chlorides
Authors: Kim So Han , Kim Min , Verkade John G. , Kim Youngjo
Published: February 2015

The N‐arylation of various amines with aryl chlorides proceeded in good‐to‐excellent yields in the presence of P[N{(p‐NMe2)C6H4CH2}CH2CH2]3N (1e, a new electron‐rich proazaphosphatrane ligand) and small amounts of Pd2(dba)3 (dba = dibenzylideneacetone). This catalytic system was also very effective for the synthesis of carbazoles.
Synthesis of Simplified Halogenated Chondramide Derivatives with Strong Cytostatic Properties
Authors: Becker Dominic , Kazmaier Uli
Published: February 2015

Removing the methyl groups and the stereogenic centers from the ω‐hydroxy acid of the chondramides results in a significant drop in the cytotoxicity of these interesting depsipeptides. This effect can be almost compensated for by introduction of a second chlorine atom on the β‐tyrosine moiety of the natural products. These simplified chondramides are much easier accessible than natural chondramides.