bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of miltiradiene by metabolically engineered Saccharomyces cerevisiae
Authors: Dai Zhubo , Liu Yi , Huang Luqi , Zhang Xueli
Published: May 2012

Metabolic engineering of microorganisms is an alternative and attractive route for production of valuable terpenoids that are usually extracted from plant sources. Tanshinones are the bioactive components of Salvia miltiorrhizha Bunge, which is a well‐known traditional Chinese medicine widely used for treatment of many cardiovascular diseases. As a step toward microbial production of tanshinones, copalyl diphosphate (CPP) synthase, and normal CPP kaurene synthase‐like genes, which convert the universal diterpenoid precursor geranylgeranyl diphosphate (GGPP) to miltiradiene (an important intermediate of the tanshinones synthetic pathway), was introduced into Saccharomyces cerevisiae, resulting in production of 4.2 mg/L miltiradiene. Improving supplies of isoprenoid precursors was then investigated for increasing miltiradiene production. Although over‐expression of a truncated 3‐hydroxyl‐3‐methylglutaryl‐CoA reductase (tHMGR) and a mutated global regulatory factor (upc2.1) gene did improve supply of farnesyl diphosphate (FPP), production of miltiradiene was not increased while large amounts of squalene (78 mg/L) were accumulated. In contrast, miltiradiene production increased to 8.8 mg/L by improving supply of GGPP through over‐expression of a fusion gene of FPP synthase (ERG20) and endogenous GGPP synthase (BTS1) together with a heterologous GGPP synthase from Sulfolobus acidocaldarius (SaGGPS). Auxotrophic markers in the episomal plasmids were then replaced by antibiotic markers, so that engineered yeast strains could use rich medium to obtain better cell growth while keeping plasmid stabilities. Over‐expressing ERG20‐BTS1 and SaGGPS genes increased miltiradiene production from 5.4 to 28.2 mg/L. Combinatorial over‐expression of tHMGR‐upc2.1 and ERG20‐BTS1‐SaGGPS genes had a synergetic effects on miltiradiene production, increasing titer to 61.8 mg/L. Finally, fed‐batch fermentation was performed, and 488 mg/L miltiradiene was produced. The yeast strains engineered in this work provide a basis for creating an alternative way for production of tanshinones in place of extraction from plant sources. Biotechnol. Bioeng. 2012; 109: 2845–2853. © 2012 Wiley Periodicals, Inc.
Physiological response of Clostridium carboxidivorans during conversion of synthesis gas to solvents in a gas‐fed bioreactor
Authors: Ukpong Michael N. , Atiyeh Hasan K. , De Lorme Marthah J.M. , Liu Kan , Zhu Xiaoguang , Tanner Ralph S. , Wilkins Mark R. , Stevenson Bradley S.
Published: May 2012

Clostridium carboxidivorans P7 is one of three microbial catalysts capable of fermenting synthesis gas (mainly CO, CO2, and H2) to produce the liquid biofuels ethanol and butanol. Gasification of feedstocks to produce synthesis gas (syngas), followed by microbial conversion to solvents, greatly expands the diversity of suitable feedstocks that can be used for biofuel production beyond commonly used food and energy crops to include agricultural, industrial, and municipal waste streams. C. carboxidivorans P7 uses a variation of the classic Wood–Ljungdahl pathway, identified through genome sequence‐enabled approaches but only limited direct metabolic analyses. As a result, little is known about gene expression and enzyme activities during solvent production. In this study, we measured cell growth, gene expression, enzyme activity, and product formation in autotrophic batch cultures continuously fed a synthetic syngas mixture. These cultures exhibited an initial phase of growth, followed by acidogenesis that resulted in a reduction in pH. After cessation of growth, solventogenesis occurred, pH increased and maximum concentrations of acetate (41 mM), butyrate (1.4 mM), ethanol (61 mM), and butanol (7.1 mM) were achieved. Enzyme activities were highest during the growth phase, but expression of carbon monoxide dehydrogenase (CODH), Fe‐only hydrogenases and two tandem bi‐functional acetaldehyde/alcohol dehydrogenases were highest during specific stages of solventogenesis. Several amino acid substitutions between the tandem acetaldehyde/alcohol dehydrogenases and the differential expression of their genes suggest that they may have different roles during solvent formation. The data presented here provide a link between the expression of key enzymes, their measured activities and solvent production by C. carboxidivorans P7. This research also identifies potential targets for metabolic engineering efforts designed to produce higher amounts of ethanol or butanol from syngas. Biotechnol. Bioeng. 2012; 109: 2720–2728. © 2012 Wiley Periodicals, Inc.
Rapidly serum‐degradable hydrogel templating fabrication of spherical tissues and curved tubular structures
Authors: Sakai Shinji , Inagaki Hitomi , Liu Yang , Matsuyama Tomohiro , Kihara Takanori , Miyake Jun , Kawakami Koei , Taya Masahito
Published: May 2012

Development of the techniques for fabricating three‐dimensional tissues still poses significant challenges for tissue engineering. We used hydrogels obtained from phenol‐substituted amylopectin (AP‐Ph) as templates for preparing multicellular spherical tissues (MSTs) and endothelialized curved tubular structures in type I collagen gel. AP‐Ph hydrogel microparticles of diameter 200 µm and fibers of diameter 500 µm disappeared within hours of soaking in a serum‐containing medium. HeLa cells and human endothelial cells were enclosed in the microparticles and hydrogel fibers, respectively, and then embedded in Ca‐alginate microcapsules or the collagen gel. The enclosed cells were released in cavities formed by hydrogel degradation in the serum‐containing medium. The released HeLa cells in the spherical cavities grew and formed MSTs, eventually filling the cavities. The spherical tissues were easily harvested by liquefying the Ca‐alginate hydrogel microcapsule membrane by chelation using sodium citrate. The released endothelial cells grew on the tubular cavity surfaces and formed tubular structures. An endothelial cell network was formed by cell migration into the collagen gel. These results demonstrate the potential of serum‐degradable AP‐Ph hydrogels in constructing three‐dimensional tissues. Biotechnol. Bioeng. 2012; 109: 2911–2919. © 2012 Wiley Periodicals, Inc.
Integration of mixing, heat transfer, and biochemical reaction kinetics in anaerobic methane fermentation
Authors: Wu Binxin
Published: May 2012

An extensive investigation of anaerobic methane fermentation requires identifying the relationship between the physical environment and biological process. In this study, a computational fluid dynamics (CFD) technique was used to characterize bacterial fermentation mechanisms intertwined with mixing and heat transfer in anaerobic digesters. The results demonstrate that the methane yield remains almost unchanged while the energy efficiency decreases with increasing mixing power in a complete‐mix digester, and that the energy output increases nonlinearly with the increase in heating energy in a plug‐flow digester. The CFD method can be applied to other bioreactors to gain valuable insights into their behavior as well. Integrating flow and temperature with kinetic behavior for anaerobic digestion not only solves the controversy about how mixing influences the digestive process, but also assists in optimizing the digester design and increasing the efficiency of energy conversion, and additionally, provides a reference for improving the mixing guidelines recommended by the U.S. Environmental Protection Agency. Biotechnol. Bioeng. 2012; 109: 2864–2874. © 2012 Wiley Periodicals, Inc.
An activated sludge modeling framework for xenobiotic trace chemicals (ASM‐X): Assessment of diclofenac and carbamazepine
Authors: Plósz Benedek Gy. , Langford Katherine H. , Thomas Kevin V.
Published: May 2012

Conventional models for predicting the fate of xenobiotic organic trace chemicals, identified, and calibrated using data obtained in batch experiments spiked with reference substances, can be limited in predicting xenobiotic removal in wastewater treatment plants (WWTPs). At stake is the level of model complexity required to adequately describe a general theory of xenobiotic removal in WWTPs. In this article, we assess the factors that influence the removal of diclofenac and carbamazepine in activated sludge, and evaluate the complexity required for the model to effectively predict their removal. The results are generalized to previously published cases. Batch experimental results, obtained under anoxic and aerobic conditions, were used to identify extensions to, and to estimate parameter values of the activated sludge modeling framework for Xenobiotic trace chemicals (ASM‐X). Measurement and simulation results obtained in the batch experiments, spiked with the diclofenac and carbamazepine content of preclarified municipal wastewater shows comparably high biotransformation rates in the presence of growth substrates. Forward dynamic simulations were performed using full‐scale data obtained from Bekkelaget WWTP (Oslo, Norway) to evaluate the model and to estimate the level of re‐transformable xenobiotics present in the influent. The results obtained in this study demonstrate that xenobiotic loading conditions can significantly influence the removal capacity of WWTPs. We show that the trace chemical retransformation in upstream sewer pipes can introduce considerable error in assessing the removal efficiency of a WWTP, based only on parent compound concentration measurements. The combination of our data with those from the literature shows that solids retention time (SRT) can enhance the biotransformation of diclofenac, which was not the case for carbamazepine. Model approximation of the xenobiotic concentration, detected in the solid phase, suggest that between approximately 1% and 16% of the total solid carbamazepine and diclofenac concentrations, respectively, is due to sorption—the remainder being non‐bioavailable and sequestered. We demonstrate the effectiveness of the model's predictive power over conventional tools in a statistical analysis, performed at four levels of structural complexity. To assess WWTP retrofitting needs to remove xenobiotic trace chemicals, we suggest using mechanistic models, e.g., ASM‐X, in regional risk assessments. For preliminary evaluations, we present operating charts that can be used to estimate average xenobiotic removal rates in WWTPs as a function of SRT and the xenobiotics mass loads normalised to design treatment capacity. Biotechnol. Bioeng. 2012; 109: 2757–2769. © 2012 Wiley Periodicals, Inc.
Implementing a new approach for the design of an e‐learning platform in engineering education
Authors: Violante Maria Grazia , Vezzetti Enrico
Published: May 2012

Modern corporations, institutions, universities and schools consider e‐education as a way of educating larger groups of students in less time and of reducing the use of various resources. Since setting up a web‐system for e‐education requires a significant amount of time, as well as the necessity of having a computer and other resources, the assessment of the goals and desired effects of the online system should be made in the preparation phase. It is important to highlight that only putting course contents on the web, without using appropriate pedagogical models and principles, without appropriate means of communication between participants and instructors and without the use of modern information technologies to present the learning content is not enough to fulfil educational goals. It should be noted that, after the substantial initial investment and excitement about the possibilities of e‐education, many sources of difficulty and dissatisfaction regarding online learning have emerged. Most e‐learning studies propose possible improvements in course material, with little attempt to explore the learners' dimension, context, pedagogical considerations or technology aspects. In this article, we have analysed the aspects that need to be considered when designing an e‐learning platform for engineering education and we have proposed a methodology, based on the Quality Function Deployment approach, useful for the preparation phase of distance learning systems. Finally, we have explained the impact of new information technologies (Web3D technologies) on online engineering education and highlighted how these tools have been implemented in the e‐learning platforms for mechanical engineering that we have developed.© 2012 Wiley Periodicals, Inc. Comput Appl Eng Educ 22:708–727, 2014; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21564
In Situ Monitoring of Cocrystallization Processes – Complementary Use of Sensing Technologies
Authors: Gagniere E. , Puel F. , Mangin D. , Valour J.‐P. , Rivoire A. , Galvan J.‐M. , Monnier O. , Klein J.‐P.
Published: May 2012

Two in situ process analytical technologies were used to investigate a cocrystallization process: a focused beam reflectance measurement probe and a video probe. The cocrystallizations were conducted batch‐wise in a stirred thermostatted vessel with carbamazepine and nicotinamide. The experiments were started in three domains of the phase solubility diagram. When carbamazepine crystals were also formed, a solution mediated phase transition from carbamazepine crystals towards cocrystals was initiated by the addition of the cocrystallizing agent (nicotinamide crystals). As the carbamazepine crystals and the carbamazepine/nicotinamide cocrystals exhibit prism‐like and needle‐like habits, respectively, it was possible to discriminate between them with the two sensors. The mechanisms involved in the solution mediated phase transition were investigated.
Effect of Supersaturation on Polymorphs of Clopidogrel Hydrogen Sulfate in Drowning‐out Crystallization
Authors: Jim M. , Kim K.‐J.
Published: May 2012

To crystallize selectively forms I and II of clopidogrel hydrogen sulfate (CHS), nucleation behavior and supersaturation level were studied in mixed solvents such as formic acid/isopropanol, N,N‐dimethylformamide/isopropanol, and N‐methylpyrrolidone/isopropanol. The effect of supersaturation on induction time and nucleation rate was evaluated by comparison between nucleation mechanisms of seeded and unseeded crystallizations. Experimental results indicate that the polymorph obtained by crystallization depends on the type of seed crystals, amount of seed crystals, and seeding point. Homogeneous nucleation was desirable for the formation of form I. Form II corresponds to primary nucleation, i.e., homogeneous and heterogeneous nucleations.
Deuterium Quantification through Deuterium‐Induced Remote1H and13C NMR Shifts
Authors: Knorr Rudolf , Stephenson David S.
Published: May 2012

Partial labeling by deuterium may be quantified through simple integrations of those1H (200 or 400 MHz) and13C (100.6 MHz) NMR resonances that are split into pairs by chemical shiftsnΔ=δ(deuterated)−δ(nondeuterated) as induced by deuterium acrossn>2 chemical bonds. The relative intensities of the two components of a pair are shown to be influenced to practically equal degrees by relaxation effects, so that a deuterium fraction may be determined from1H and13C integral pairs at more remote molecular positions under the routine conditions of fast accumulative spectral acquisition.
Large Eddy Simulation of Turbulent Reacting Mixing of Liquids in a Coaxial Jet Mixer
Authors: Walter Matthias , Kornev Nikolai , Hassel Egon
Published: May 2012

Large eddy simulation is used to investigate passive and reactive scalar mixing at high Reynolds Re and Schmidt Sc numbers in order to prove capability of the LES‐SGS micromixing approaches based on the eddy dissipation and DQMOM‐IEM models properly simulating liquid reacting flows. Simulations were performed for a fast neutralization reaction in a confined jet reactor. The mean profiles for passive scalar agree well with measurements. It was shown that the most contribution to the scalar variance is made by large scale motions whereas the contribution of fine scales smaller than typical inertial range scales is negligible. Thus, the existing LES models are capable of predicting the scalar variance at large Sc numbers. The results obtained for reactive transport revealed discrepancies in the determination of micromixing rate and product concentration. A special study was performed to investigate the dynamics of fine structures using locally refined box embedded into global grid. Typical statistical properties of fine structures were reproduced numerically.
A mechanistic study of agglomeration in fluidised beds at elevated pressures
Authors: Mansourpour Zahra , Mostoufi Navid , Sotudeh‐Gharebagh Rahmat
Published: May 2012

Effect of operating pressure on the hydrodynamics of agglomerating gas–solid fluidised bed was investigated using a combination of discrete element method (DEM) for describing the movement of particles and computational fluid dynamic (CFD) for describing the flow of the gas phase. The inter‐particle cohesive force was calculated based on a time dependent model developed for solid bridging by the viscous flow. Motion of agglomerates was described by the multi‐sphere method. Fluidisation behaviour of an agglomerating bed was successfully simulated in terms of increasing the size of agglomerates. The results showed that increasing the operating pressure postpones de‐fluidisation of the bed. Since the DEM approach is a particle level simulation and study about particle–particle interactions is possible, a micro‐scale investigation in terms of cohesive force and repulsive force during agglomeration at elevated pressures was done. The micro‐scale results showed that although the number of contacts between particles was decreased by increasing operating pressure, stronger solid bridge formed between colliding particles at higher pressures. © 2012 Canadian Society for Chemical Engineering
Crystal Structure and Photoluminescence of a Tetranuclear Cadmium Complex
Authors: Shi Juan , Zhang Zunting
Published: May 2012

A novel tetranuclear cadmium complex ([{Cd(C15H8O7S)(H2O)(DMSO)}3{Cd(C15H8O7S)(H2O)2}]·3DMSO·H2O) was obtained by the self‐assembly of Cd(II) with 5,7‐dihydroxyflavone‐6‐sulfonate. The complex was characterized by 1H NMR, IR, elemental analysis and X‐ray single‐crystal diffraction studies. It crystallizes in triclinic, space group $ P {\bar 1} $. In the complex, the chelate atoms of Cd(II) are all from oxygen. Four Cd(II) are connected via the carbonyl and 5‐hydroxyanion of four ligands and form an approximate square. Four ligands locate at two sides of the square, and two of them at the same side are almost parallel and exist aromatic π‐π stacking. Ligands on the opposite side of the square are nearly perpendicular. The result of the luminescent studies indicated that the solid of the complex shwed photoluminescent properties because of a combination of coordination, hydrogen bonding and π‐π stacking interaction in the molecule structure. The complex emits green fluorescence (λem=496 nm) when it is excited at the wavelength of 440 nm.
Synthesis, Characterization, and Highly Selective Ethylene Dimerization to 1‐Butene of [O−NX]Ni(II) Complexes
Authors: Xu Chongjie , Shen Qi , Sun Xiuli , Tang Yong
Published: May 2012

A series of nickel(II) complexes have been synthesized and characterized. Molecular structure analysis exhibits that a square planar geometry around nickel is adopted. Upon activation with MAO, these nickel(II) complexes are efficient in catalyzing the ethylene dimerization, providing 1‐butene with an activity of up to 1.4×107 g/(mol·h·atm). The heteroatoms of the sidearm in the complexes were proved to have great impact on the activity and selectivity of 1‐butene.
Synthesis, Characterization, Optical and Electrochemical Properties of Fulleropyrrolidines Containing Trifluoromethyl Group
Authors: Li Xiangzi , Yu Rui , Fang Shu , Wei Xianwen
Published: May 2012

Four novel [60]fullerene pyrrolidines containing trifluoromethyl (CF3) group have been synthesized via 1,3‐dipolar cycloaddition reaction, which have been characterized by UV‐Vis spectroscopy, fourier transform infrared spectroscopy, matrix‐assisted laser desorption ionization‐time of flight mass spectroscopy, and1H,13C,19F nuclear magnetic resonance spectrometer (1H NMR,13C NMR,19F NMR). Their optical and electrochemical properties have been studied, and the results show that those fulleropyrrolidines containing CF3group have good fluorescence and electrochemical properties. Compared with C60, they have negative shifts in varying degrees for half‐wave potentials, and may have potential applications for photovoltaic conversion materials since their lowest unoccupied molecular orbital (LUMO) levels are close to that of [6,6]‐phenyl‐C61‐butyric acid methyl ester.
Acyclic Palladium(II)‐N‐heterocyclic Carbene Metallacrown Ether Complexes: Synthesis, Structure and Catalytic Activity
Authors: Zhang Weixi , Zhang Xiaoqin , Luo Meiming
Published: May 2012

Novel acyclic Pd(II)‐N‐heterocyclic carbene (NHC) metallacrown ethers 5a, 5b have been synthesized. Reaction of the imidazolium salts bearing a long polyether chain with Ag2O afforded Ag‐NHC complexes, which then reacted as carbene transfer agent with PdCl2(MeCN)2 to give the desired acyclic Pd(II)‐NHC metallacrown ether complexes 5a and 5b. The 1H NMR and 13C NMR spectra show 5a and 5b exist as mixtures of cis and trans isomers in solution. The trans isomer of 5a was characterized by X‐ray diffraction, which clearly demonstrated two pseudo‐crown ether cavities in trans‐5a. Pd(II)‐NHC complexes 5a and 5b have been shown to be highly effective in the Suzuki‐Miyaura reactions of a variety of aryl bromides in neat water without the need of inert gas protection.
Antimicrobial Aromatic Polyketides from Gorgonian‐Associated Fungus, Penicillium commune 518
Authors: Wang Junfeng , Liu Peipei , Wang Yi , Wang Hui , Li Jing , Zhuang Yibin , Zhu Weiming
Published: May 2012

Seven new aromatic polyketides, communols A–G (1–7), were isolated and identified from the fermentation broth of Penicillium commune 518, a marine‐derived fungus associated with the Gorgonian, Muricella abnormalis. The new structures of 1–7 were determined by spectroscopic analysis and X‐ray single crystal diffraction. Among them, communol D (4) was the first example of a naturally occurring aromatic polyketide with a sulfoxide group from marine fungi. Compounds 1, 6, and 7 all showed moderate antimicrobial activities against Escherichia coli and Enterobacter aerogenes with MIC values of 4.1/16.4, 6.4/25.8, and 23.8/23.8 µmol·L−1, respectively.
Novel 1D Copper(II) Helical Chain Formed by Weak Coordination‐driven Self‐assembly: Synthesis, Structure, and Magnetic Property
Authors: Huang Wanyun , Chen Zilu , Zou Huahong , Liu Dongcheng , Liang Fupei
Published: May 2012

A novel 1D copper(II) helical chain is constructed through the connection of tetranuclear copper(II) units [Cu4(L)(Py)4] (H8L=N,N′‐(BINOL‐3,3′‐dicarboxyl)‐disalicylhydrazide, where BINOL is 1,1′‐binaphthalenyl‐2,2′‐diol, py=pyridine) by weak coordination‐driven self‐assembly, and characterized by IR, single crystal X‐ray diffraction, thermogravimetric analysis, and X‐ray power diffraction analysis. Interestingly, the helical chains are packed in an alternating left‐(M) and right‐handed (P) chirality, the orientation of the helices was determined by the axial chirality of the ligand. The complex shows antiferromagnetic interactions between the copper centers.
Stable Water‐dispersed CdTe Nanocrystals Dependent on Stoichiometric Ratio of Cd to Te Precursor
Authors: Zhang Xurui , Wang Lixin , Guo Jia , Yang Wuli
Published: May 2012

The improved properties of CdTe nanocrystals (NCs) synthesized by hydrothermal method were introduced. The experimental results indicated that the NCs properties could be dramatically influenced by means of changing Cd‐to‐Te molar ratio (the molar ratio of CdCl2 and NaHTe in the precursor) of the MPA‐capped CdTe NCs. With the increase of the ratio from 2:1 to 10:1, the formation time of near‐infrared‐emitting CdTe NCs was shortened. In particular, high Cd‐to‐Te molar ratio brought about MPA‐capped CdTe NCs of superior radical oxidation‐resistance and photostability. As a result, the optimum ratio was found to be 8:1 or 10:1 in the study in order to efficiently attain stable, water‐dispersed CdTe NCs.
A Facile Synthesis of Enantiomerically Pure (R)‐6‐Arylbinols
Authors: Wang Wenling , Long Yuhua , Zou Zhifu , Yang Dingqiao
Published: May 2012

This work reported a convenient method for the preparation of enantiomerically pure 6‐aryl‐2,2′‐dihydroxy‐1,1′‐binaphthyl derivatives starting from the commercially available (R)‐2,2′‐hydroxy‐1,1′‐binaphthyl [(R)‐1] via bromination, hydrolysis and Suzuki cross coupling reaction. This novel synthetic method was characterized with high regioselectivity, simple operation, mild reaction conditions, and excellent yield (up to 73%). On the other hand, we synthesized the target unknown compounds, which were confirmed by IR, 1H NMR, 13C NMR, MS and elementary analysis.
Iron‐Promoted Practical One‐Pot Synthesis of 2,5‐Disubstituted Oxazoles
Authors: Chen Songhui , Bai Donghu , Shi Feng , Li Jian , Li Chunju , Jia Xueshun
Published: May 2012

A practical one‐pot protocol for the synthesis of 2,5‐disubstituted oxazoles from 1‐aryl‐2‐nitroethanones was reported. In the presence of iron/AcOH in acetonitrile, the reaction of 1‐aryl‐2‐nitroethanones with trimethyl orthoacetate or trimethyl orthobenzoate delivered the corresponding 2,5‐disubstituted oxazoles in moderate to good yields.
Synthesis and Anti‐tumor Evaluation of Novel C‐37 Modified Derivatives of Gambogic Acid
Authors: Li Xiang , Zhang Xiaojin , Sun Haopeng , Zhang Lei , Gao Yuan , Wang Jinxin , Guo Qinglong , You Qidong
Published: May 2012

Gambogic acid (GA, 1), the most prominent representative of Garcinia natural products, has been reported to be a promising anti‐tumor agent. In order to further explore the structure‐activity relationship of GA and discover novel GA derivatives as anti‐tumor agents, 17 novel C‐37 modified derivatives of GA were synthesized and evaluated for their in vitro anti‐tumor activities against A549, HCT‐116, BGC‐823, HepG2 and MCF‐7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, compound 8 was almost 5–10 folds more active than GA against A549 and BGC‐823 cell lines with the IC50 values of 0.12 µmol·L−1 and 0.57 µmol·L−1, respectively. Chemical modification at C‐37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug‐like properties. These findings will enhance our understanding of the structure‐activity relationship (SAR) of GA and lead to the discovery of novel GA derivatives as potential anti‐tumor agents.
Synthesis, Characterization, Antibacterial and Antifungal Activity of Yttrium(III) Complexes Including 1,10‐Phenanthroline
Authors: Cai Mengjun , Chen Jianding , Taha Mohamed
Published: May 2012

Two rare metal coordination complexes of yttrium(III) including 1,10‐phenanthroline, Y(phen)2(NO3)3 and (phenH)2[Y2(pydc)3(NO3)2·6H2O] (phen=1,10‐phenanthroline, pydc=2,6‐pyridinedicarboxylate), and a proton transfer compound (phenH+)2(pydc2−) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra (IR), nuclear magnetic resonance (NMR) and thermal analysis. The proposed structures of yttrium complexes were exhibited. The in vitro biological activities of the newly synthesized complexes have also been investigated against Bacillus coli, Staphylococcus aureus and Candida albicans. The results showed that yttrium(III) complexes including 1,10‐phenanthroline exhibited better antibacterial/antifungal activity than their ligands and corresponding compounds.
A phase 1 study of efatutazone, an oral peroxisome proliferator‐activated receptor gamma agonist, administered to patients with advanced malignancies
Authors: Pishvaian Michael J. , Marshall John L. , Wagner Andrew J. , Hwang Jimmy J. , Malik Shakun , Cotarla Ion , Deeken John F. , He A. Ruth , Daniel Hirut , Halim Abdel‐Baset , Zahir Hamim , Copigneaux Catherine , Liu Kejian , Beckman Robert A. , Demetri George D.
Published: May 2012

BACKGROUND:

Efatutazone (CS‐7017), a novel peroxisome proliferator‐activated receptor gamma (PPARγ) agonist, exerts anticancer activity in preclinical models. The authors conducted a phase 1 study to determine the recommended phase 2 dose, safety, tolerability, and pharmacokinetics of efatutazone.

METHODS:

Patients with advanced solid malignancies and no curative therapeutic options were enrolled to receive a given dose of efatutazone, administered orally (PO) twice daily for 6 weeks, in a 3 + 3 intercohort dose‐escalation trial. After the third patient, patients with diabetes mellitus were excluded. Efatutazone dosing continued until disease progression or unacceptable toxicity, with measurement of efatutazone pharmacokinetics and plasma adiponectin levels.

RESULTS:

Thirty‐one patients received efatutazone at doses ranging from 0.10 to 1.15 mg PO twice daily. Dose escalation stopped when maximal impact on PPARγ‐related biomarkers had been reached before any protocol‐defined maximum‐tolerated dose level. On the basis of a population pharmacokinetic/pharmacodynamic analysis, the recommended phase 2 dose was 0.5 mg PO twice daily. A majority of patients experienced peripheral edema (53.3%), often requiring diuretics. Three episodes of dose‐limiting toxicities, related to fluid retention, were noted in the 0.10‐, 0.25‐, and 1.15‐mg cohorts. Of 31 treated patients, 27 were evaluable for response. A sustained partial response (PR; 690 days on therapy) was observed in a patient with myxoid liposarcoma. Ten additional patients had stable disease (SD) for ≥60 days. Exposures were approximately dose proportional, and adiponectin levels increased after 4 weeks of treatment at all dose levels. Immunohistochemistry of archived specimens demonstrated that PPARγ and retinoid X receptor expression levels were significantly greater in patients with SD for ≥60 days or PR (P = .0079), suggesting a predictive biomarker.

CONCLUSIONS:

Efatutazone demonstrates acceptable tolerability with evidence of disease control in patients with advanced malignancies. Cancer 2012. © 2012 American Cancer Society.
Conditional probability of long‐term survival in glioblastoma
Authors: Johnson Derek R. , Ma Daniel J. , Buckner Jan C. , Hammack Julie E.
Published: May 2012

BACKGROUND:

Advances in glioblastoma care have resulted in a larger proportion of patients surviving beyond 2 years after diagnosis. It is not clear how long‐term survivors should be counseled with respect to future prognosis, or what factors influence that prognosis. The conditional probability of survival was evaluated from multiple time points in patients with glioblastoma, using Surveillance, Epidemiology, and End Results (SEER) data.

METHODS:

Patients diagnosed with glioblastoma from 1998 to 2008 who were treated with radiation‐containing regimens were identified within SEER data. Conditional survival probabilities from multiple survival points were calculated. Cox proportional hazards models were constructed to identify predictors of survival from diagnosis and from 1 and 2 years after diagnosis.

RESULTS:

A total of 10,022 patients with glioblastoma met study inclusion criteria; median survival was 12.61 months. Conditional probability of surviving an additional 2 years ranged from 19.8% at diagnosis to 65.9% at 5 years after diagnosis. The proportion of patients surviving 12 months from time of diagnosis as well as from 6, 12, and 18 months after diagnosis was significantly higher in patients diagnosed in 2005 through 2008 than those diagnosed in 1998 through 2004. Of demographic and treatment‐related factors evaluated, only age was associated with hazard of death at diagnosis and 1 and 3 years after diagnosis (P < .0001 at each time point).

CONCLUSIONS:

Patients surviving past 2 years from diagnosis have a relatively favorable conditional probability of survival into the future compared to newly diagnosed patients. This effect becomes more pronounced with increasing time since diagnosis. These data will assist in the counseling of glioblastoma survivors. Cancer 2012. © 2012 American Cancer Society.
The Effect of Boron Doping Level on The Morphology and Structure of Ultra/Nanocrystalline Diamond Films
Authors: Souza Fernando A. , Azevedo Adriana F. , Giles Carlos , Saito Eduardo , Baldan Maurício R. , Ferreira Neidenêi G.
Published: May 2012

In this work, boron‐doped nanocrystalline diamond (BDND) films are grown on silicon substrates by hot‐filament (HF)CVD in Ar/H2/CH4 gas mixtures. In this study, the transition from ultra‐nanocrystalline to nanocrystalline diamond films is clearly shown by the addition of boron dopant to the growth of the gas mixture. The doping process consists of an additional H2 line passing through a bubbler containing B2O3 dissolved in methanol with various B/C ratios. Five sample sets are obtained with doping in the methanol bubbler solution of 2 000, 5 000, 10 000, 20 000, and 30 000 ppm for a 16 h growth time. The morphology, roughness, and structure of these films have markedly different properties. The cross‐section of the films is characterized by scanning electron microscopy (SEM) showing the transition from ultra‐nanocrystalline growth (renucleation process) to a columnar structure of nanocrystalline films. The acceptor density values, evaluated by Raman spectra and by Mott‐Schottky plot analysis, vary from 1020 to 1021 B cm−3 as the doping level increases. The grain size and the relative intensity of the (111)/(220) peaks are obtained from X‐ray diffraction (XRD) patterns of the films. The diamond average grain size increases from 10 to 35 nm for films with 2 000 and 30 000 ppm B/C, respectively, in the methanol bubbler solution. The preferential orientation also changes, from (220) to (111), as the boron doping level increases.
Structure and Dielectric Study of Poly(α,α difluoro‐p‐xylylene) Thin Films: Highlight of the Substrate Temperature Effect
Authors: Kahouli Abdelkader , André Emmanuel , Sylvestre Alain , Pairis Sébastien , Jomni Fathi , Yangui Béchir , Garden Jean‐Luc
Published: May 2012

Research on poly(α,α difluoro‐p‐xylylene) thin films is described and summarized. The important physicochemical and dielectric properties are investigated. For this, characterization tools that can provide information on the nature of structural and physicochemical according substrate temperature are used. A summary of the main properties of poly(α,α difluoro‐p‐xylylene) is presented.
β‐Diketiminato–Alkaline Earth Cationic Complexes: Synthesis, Structures, Lactide Polymerization and Unusual Oxidative Reactivity of the Ancillary Ligand
Authors: Liu Bo , Dorcet Vincent , Maron Laurent , Carpentier Jean‐François , Sarazin Yann
Published: May 2012

Well‐defined (β‐diketiminate)calcium and ‐strontium cationic complexes paired with weakly coordinating anions have been prepared in high yields by straightforward protocols. These highly electrophilic species are efficient catalysts for the immortal ring‐opening polymerization of lactide and display unusual reactivity by providing a unique example of oxidation of a {BDIiPr} core to give a diiminoalkoxide.
Highly Selective Primary Alkoxycarboxylation and Esterification of Unprotected Pyranose Derivatives Mediated by Scandium(III) Triflate Catalysis
Authors: McClure Michael S. , Berry Malcolm B. , Caine Darren , Crawford Claire , Crump Brian C. , Glover Bobby N. , Kedia Sandeep B. , Millar Alan , Mitchell Mark B. , Nichols Christopher J. , Patterson Daniel E. , Powers Jeremiah
Published: May 2012

A highly selective method for the alkoxycarboxylation and acylation of primary alcohols of pyranose derivatives is described. The reaction is high yielding and proceeds under mild conditions with 0.15–1 mol‐% Sc(OTf)3 used in combination with anhydrides or pyrocarbonates at 40–50 °C. Selectivities observed for alkoxycarboxylation of unprotected pyranose derivatives are > 95 %, and this constitutes a significant advantage over existing methods. Mechanistic implications, including the role of steric demand and metal–heteroatom coordination are also discussed.
Two‐Photon Fluorescent Probes for Bioimaging
Authors: Yao Sheng , Belfield Kevin D.
Published: May 2012

With the extensive use of two‐photon fluorescence microscopy (2PFM) in the biomedical field, the need for development of fluorescent probes with improved two‐photon fluorescence (2PF) properties has triggered extensive studies in the synthesis of new probes that undergo efficient two‐photon absorption (2PA). In order to provide a more comprehensive comparison of fluorophores for 2PF bioimaging, a figure of merit (FM) was developed by normalizing the 2PA action cross‐section, a commonly used parameter for characterizing bioimaging 2PF probes, by the photodecomposition quantum yield. Another important aspect of developing 2PA fluorophores is hydrophilicity. Although hydrophilic fluorophores are generally preferred in 2PFM bioimaging, hydrophobic fluorophores are typically easier to synthesize and purify, and have been used successfully in 2PFM bioimaging. The methodologies of dispersing hydrophobic fluorophores into aqueous media, such as in a DMSO/water mixture, micelles, silica nanoparticles, or forming polymer nanoparticles, are reviewed. The design and synthesis of hydrophilic 2PA fluorophores, achieved by introducing polyethylene glycol (PEG), anionic acid groups, cationic ammonium salt, and PAMAM dendrimers, is presented. Introduction of specificity to target certain biomarkers via labeling of antibodies, DNA, smallbioactive molecules, and peptides, and for the sensing of sepcific cations and pH, is also reviewed.
Silylcyanation of Aldehydes, Ketones, and Imines Catalyzed by a 6,6′‐Bis‐sulfonamide Derivative of 7,7′‐Dihydroxy‐8,8′‐biquinolyl (azaBINOL)
Authors: Sephton Selena Milicevic , Wang Chao , Zakharov Lev N. , Blakemore Paul R.
Published: May 2012

6,6′‐Bis(methylaminosulfonyl)‐7,7′‐dihydroxy‐8,8′‐biquinolyl (3) catalyzes (5–10 mol‐%) the addition of trimethylsilyl cyanide to aldehydes (aryl, alkyl, and α,β‐unsaturated; 42–92 % yields), ketones (aryl alkyl, dialkyl; 22–82 % yields), andN‐benzylaldimines (14–78 % yields) in toluene (0 °C or room temp.) to give the expected cyanohydrin and Strecker adducts following desilylation. Among a series of closely related compounds lacking any one of their defining structural features, bis‐sulfonamide3and itsN,N′‐dimethyl derivative are exceptional in catalyzing the silylcyanation of benzaldehyde in the absence of all other additives. Hammett analysis of the competitive silylcyanation ofpara‐substituted benzaldehydes catalyzed by3showed a linear free‐energy relationship (R2= 0.928) with a modest positive reaction constant (ρ= +1.52). X‐ray diffraction analysis of (±)‐3indicated acisoidbiaryl conformation and the existence of an intramolecular hydrogen bond between C7′–OH and C7–O. Resolution of (±)‐3was achieved by HPLC separation of its tetravalerate derivative on a chiral stationary phase. The absolute configurations of the optical isomers of3were assigned by correlation of the ECD spectra with those of related biquinolyls of known configuration. The silylcyanation of aldehydes catalyzed by (–)‐(aR)‐3leads to cyanohydrins with a preference for the (S)‐configured product with aneeof <10 %. The organocatalytic action of3is ascribed to hydrogen bonding and Brønsted acid catalysis effects that are dependent on its acidifying sulfonamide groups, general base capability, and interannular proximity effects made possible by the biaryl structure.
Correct treatment of rotation of sliding surfaces in a kinematic model of the triple friction pendulum bearing
Authors: Becker Tracy C. , Mahin Stephen A.
Published: May 2012

This paper addresses the treatment of the rotation of the internal components of the triple friction pendulum (TFP) isolation bearing in a numerical model previously presented by the authors. The numerical model is based on the kinematic behavior of the individual sliding surfaces and the constitutive relationships between them. The modification suggested in this paper improves the performance of the model so that the results exactly match that of the one‐dimensional piecewise linear behavior previously derived for the TFP bearing for restricted properties. The improved numerical model simulates bidirectional shear response and places no a priori restrictions on the bearing properties. The modification is put in the form of a technical communication so that the notation used and the basis of the correction could be presented with adequate clarity and so that an example of the benefit of the correction could be presented. Copyright © 2012 John Wiley & Sons, Ltd.
Exploiting genetic variation to improve wheat composition for the prevention of chronic diseases
Authors: Shewry Peter R. , Ward Jane L.
Published: May 2012

The increasing global population places a clear priority on increasing food production. However, the continued undernourishment of a significant proportion of the global population is accompanied by increases in developed and rapidly developing countries of over‐consumption, particularly of highly refined processed foods which are rich in starch, sugars, and fats, including products made from white wheat flour. This diet combined with an increasingly sedentary lifestyle is associated with a cluster of symptoms which have been termed the metabolic syndrome and are associated with increased risk of type 2 diabetes, atherosclerosis, cardiovascular disease, and forms of cancer. There is clear evidence that the consumption of either wholegrain cereals or components present in these (notably dietary fiber) has beneficial effects in reducing the risk of the metabolic syndrome and associated diseases. This article therefore reviews the major groups of bioactive components present in the wheat grain and discusses strategies for manipulating their amounts and compositions to increase the health benefits of both wholegrain and white flour products.
Association Testing for Next‐Generation Sequencing Data Using Score Statistics
Authors: Skotte Line , Korneliussen Thorfinn Sand , Albrechtsen Anders
Published: May 2012

The advances in sequencing technology have made large‐scale sequencing studies for large cohorts feasible. Often, the primary goal for large‐scale studies is to identify genetic variants associated with a disease or other phenotypes. Even when deep sequencing is performed, there will be many sites where there is not enough data to call genotypes accurately. Ignoring the genotype classification uncertainty by basing subsequent analyses on called genotypes leads to a loss in power. Additionally, using called genotypes can lead to spurious association signals. Some methods taking the uncertainty of genotype calls into account have been proposed; most require numerical optimization which for large‐scale data is not always computationally feasible. We show that using a score statistic for the joint likelihood of observed phenotypes and observed sequencing data provides an attractive approach to association testing for next‐generation sequencing data. The joint model accounts for the genotype classification uncertainty via the posterior probabilities of the genotypes given the observed sequencing data, which gives the approach higher power than methods based on called genotypes. This strategy remains computationally feasible due to the use of score statistics. As part of the joint likelihood, we model the distribution of the phenotypes using a generalized linear model framework, which works for both quantitative and discrete phenotypes. Thus, the method presented here is applicable to case‐control studies as well as mapping of quantitative traits. The model allows additional covariates that enable correction for confounding factors such as population stratification or cohort effects. Genet. Epidemiol. 36:430‐437, 2012. © 2012 Wiley Periodicals, Inc.
The Relationships among Internal Marketing, Job Satisfaction, Relationship Marketing, Customer Orientation, and Organizational Performance: An Empirical Study of TFT‐LCD Companies in Taiwan
Authors: Wu Wann‐Yih , Tsai Chia‐Chun , Fu Chen‐Su
Published: May 2012

The thin film technology liquid‐crystal displays (TFT‐LCD) industry has become one of the main industries in Taiwan. In this research, we take Taiwanese TFT‐LCD industrial companies as the research objects and try to identify the interrelationships among internal marketing, job satisfaction, relationship marketing, customer orientation, and organizational performance. Although these companies are classified as part of the manufacturing industry, it is suggested that their service components could be the focus of greater attention to enhance the success of their business operations. Analytical results indicate that internal marketing, job satisfaction, and customer orientation have significant influences on relationship marketing as well as the organizational performance of TFT‐LCD manufacturing companies. Therefore, Taiwan TFT‐LCD manufacturing companies need to implement relationship marketing continuously, increase employee job satisfaction, and inspire employees to become more customer oriented in order to increase productivity. © 2012 Wiley Periodicals, Inc.
Effectiveness of the Smart Healthcare Glove System for Elderly Persons with Hypertension
Authors: Kim Ryang‐Hee , Cho Gilsoo
Published: May 2012

With the global population growth of elderly persons, there has been a tendency toward higher quality of life, along with continually increasing expectations and needs for enhanced health care for elderly persons. The purposes of this research were to develop the E‐textile–based Smart Healthcare Glove System (SHGS) with Transcutaneous Electrical Nerve Stimulator (TENS) as a health care device for the elderly hypertensive, and to evaluate the effectiveness of SHGS for hypertensive treatment. The SHGS consists of an inner glove with sensor‐embedded conductive textiles; an outer glove; a TENS for electrical stimulation; and an arm band for a ubiquitous health care wearable device. The SHGS with TENS is used for hypertension treatment and care by electrically stimulating meridian points on the palm. The health care performance test was carried out with a dozen elderly female patients (six Senior‐old‐ageing and six Old‐ageing groups) suffering from hypertension, and was conducted to measure blood pressure and pulse rate before and after wearing the SHGS with TENS for 15 min. Significantly, this study found that the mean blood pressure of all 12 patients after wearing SHGS decreased from 142.58 ± 9.90/82.46 ± 4.45 mmHg to 119.83 ± 9.23/75.79 ± 4.90 mmHg in systolic blood pressure (p < .001) as well as diastolic blood pressure (p < .01) by paired t test. Also, the mean blood pressure of chronic hypertensive patients decreased significantly from 149.25 ± 9.45/82.75 ± 2.70 mmHg to 125.33 ± 9.78/76.67 ± 3.31 mmHg in systolic blood pressure (p < .001). In addition, there was a significant difference in blood pressure before and after wearing the SHGS by Wilcoxon signed rank test (p value: 0.0313, 0.0005). These results suggest that SHGS decreases blood pressure, improves irregular blood circulation, and can be an effective high‐tech health care device for elderly hypertensive patients. Although this study used only elderly participants, the results of the study may be generalized to hypertensive patients at any age. © 2012 Wiley Periodicals, Inc.