bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial AAV‐IFN‐β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model
Authors: GuhaSarkar Dwijit , Neiswender James , Su Qin , Gao Guangping , Sena‐Esteves Miguel
Published: January 2017

The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard‐of‐care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon‐beta (IFN‐β) gene therapy by locally administered adeno‐associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models. First, we show that a single intracranial injection of AAV encoding human IFN‐β eliminates invasive human GBM8 tumors and promotes long‐term survival. Next, we screened five AAV‐IFN‐β vectors with different promoters to drive safe expression of mouse IFN‐β in the brain in the context of syngeneic GL261 tumors. Two AAV‐IFN‐β vectors were excluded due to safety concerns, but therapeutic studies with the other three vectors showed extensive tumor cell death, activation of microglia surrounding the tumors, and a 56% increase in median survival of the animals treated with AAV/P2‐Int‐mIFN‐β vector. We also assessed the therapeutic effect of combining AAV‐IFN‐β therapy with temozolomide (TMZ). As TMZ affects DNA replication, an event that is crucial for second‐strand DNA synthesis of single‐stranded AAV vectors before active transcription, we tested two TMZ treatment regimens. Treatment with TMZ prior to AAV‐IFN‐β abrogated any benefit from the latter, while the reverse order of treatment doubled the median survival compared to controls. These studies demonstrate the therapeutic potential of intracranial AAV‐IFN‐β therapy in a highly migratory GBM model as well as in a syngeneic mouse model and that combination with TMZ is likely to enhance its antitumor potency.
Reply to comment by Tan et al. on “Sandbox modeling of evolving thrust wedges with different preexisting topographic relief: Implications for the Longmen Shan thrust belt, eastern Tibet”
Authors: Sun Chuang , Jia Dong , Yin Hongwei , Chen Zhuxin , Li Zhigang , Li Shen , Wei Dongtao , Li Yiquan , Yan Bin , Wang Maomao , Fang Shaozhi , Cui Jian
Published: January 2017

Tan et al. comment that the preexisting topographic relief in our sandbox is opposed to its prototype in the central Longmen Shan. Therefore, the comparison between our sandbox modeling and the natural topography is questionable and does not agree with our conclusion that the Xiaoyudong fault is a tear fault. First, we are grateful to the authors for their approval of our sandbox modeling and its contribution to understanding fault behavior within thrust wedges. However, after reading the comment carefully, we found that they misunderstood the meaning of topographic relief we conveyed. In response, we would like to address the differences between the topography in their comment and the orogen‐scale topography we investigated in our modeling to defend our conclusion.
Dynamics of soil organic carbon and nitrogen following agricultural abandonment in a karst region
Authors: Li Dejun , Wen Li , Yang Liqiong , Luo Pan , Xiao Kongcao , Chen Hao , Zhang Wei , He Xunyang , Chen Hongsong , Wang Kelin
Published: January 2017

Agricultural abandonment is regarded as a major driver of soil organic carbon (C) dynamics, but the mechanisms underlying the direction and magnitude of soil C dynamics following agricultural abandonment are poorly understood. Here dynamics of soil C and N contents during postagricultural succession were investigated in areas underlain by dolomite or limestone by using a space‐for‐time substitution approach in a karst region, southwest China. One hundred twenty‐five sites from cropland, grassland, shrubland, and secondary forest were selected to represent different succession stages. Overall, soil C and N contents were greater (P < 0.05) over limestone than over dolomite mainly due to significantly greater contents of soil C and N in the cropland and grassland underlain by limestone. Both soil C and N contents were lowest in the cropland while highest in the forest. Further analysis indicated that the patterns of soil C and N dynamics differed between the two lithology types. Soil C and N contents increased significantly from cropland to forest over dolomite, while varied insignificantly among succession stages over limestone. Exchangeable calcium explained most of soil C and N variance. We proposed that higher dissolution rate of limestone could replenish the lost calcium so that the calcium levels, and in turn soil C and N contents, were stable from the cropland to the forest. Nevertheless, due to relatively low dissolution rate for dolomite, the calcium level was depleted in the cropland. Following agricultural abandonment, calcium level recovered due to decreased loss, which in turn resulted in recovery of soil C and N.
Controlled Fabrication of Hierarchically Structured Nitrogen‐Doped Carbon Nanotubes as a Highly Active Bifunctional Oxygen Electrocatalyst
Authors: Zhao Xianglong , Li Feng , Wang Ruining , Seo Jeong‐Min , Choi Hyun‐Jung , Jung Sun‐Min , Mahmood Javeed , Jeon In‐Yup , Baek Jong‐Beom
Published: January 2017

Hierarchically structured nitrogen‐doped carbon nanotube (NCNT) composites, with copper (Cu) nanoparticles embedded uniformly within the nanotube walls and cobalt oxide (CoxOy) nanoparticles decorated on the nanotube surfaces, are fabricated via a combinational process. This process involves the growth of Cu embedded CNTs by low‐ and high‐temperature chemical vapor deposition, post‐treatment with ammonia for nitrogen doping of these CNTs, precipitation‐assisted separation of NCNTs from cobalt nitrate aqueous solution, and finally thermal annealing for CoxOy decoration. Theoretical calculations show that interaction of Cu nanoparticles with CNT walls can effectively decrease the work function of CNT surfaces and improve adsorption of hydroxyl ions onto the CNT surfaces. Thus, the activities of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) are significantly enhanced. Because of this benefit, further nitrogen doping, and synergistic coupling between CoxOy and NCNTs, Cu@NCNT/CoxOy composites exhibit ORR activity comparable to that of commercial Pt/C catalysts and high OER activity (outperforming that of IrO2 catalysts). More importantly, the composites display superior long‐term stability for both ORR and OER. This simple but general synthesis protocol can be extended to design and synthesis of other metal/metal oxide systems for fabrication of high‐performance carbon‐based electrocatalysts with multifunctional catalytic activities.
Enzymatic N‐Glycosylation of Diverse Arylamine Aglycones by a Promiscuous Glycosyltransferase from Carthamus tinctorius
Authors: Xie Kebo , Chen Ridao , Chen Dawei , Li Jianhua , Wang Ruishan , Yang Lin , Dai Jungui
Published: January 2017

A new glycosyltransferase (UGT71E5) from Carthamus tinctorius exhibited a robust promiscuity towards 30 structurally diverse drug‐like aromatic amine scaffolds, making it the first reported glycosyltransferase capable of catalyzing N‐glycosylation with multiple diverse nitrogen‐heterocyclic aromatic compounds. The catalytic promiscuity and reversibility of UGT71E5 was exploited to generate the rare N‐glycoside from the abundant O‐glycoside with high efficiency. These findings demonstrate the significant potential of UGT71E5 in the enzymatic synthesis of diverse bioactive N‐glycosides.

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The Transition From Emergency Medicine Resident to Critical Care Fellow: A Road Map
Authors: Johnson Nicholas J. , Maher Patrick J. , Badulak Jenelle , Luks Andrew M.
Published: January 2017

Emergency medicine (EM) residents now have a number of opportunities for fellowship training in critical care medicine (CCM). The aim of this review is to help EM residents navigate the application process, transition to fellowship, and start planning their careers beyond fellowship. Pathways to advanced training in CCM available for EM residents include internal medicine‐CCM, anesthesiology‐CCM, surgical critical care, and neurocritical care. Each has unique prerequisites, application timelines, and training requirements. EM residency graduates generally already have well‐developed crisis management and team leadership skills and excel with procedures such as airway management, vascular access, and bedside ultrasound. Potential areas for growth for EM trainees include critical care physiology, end‐of‐life care, longitudinal inpatient care, and perioperative medicine. Career opportunities for physicians trained in EM and CCM are diverse and include options in community or academic settings. Some choose EM or CCM exclusively or engage in a mix of both. Academic positions with joint opportunities in EM and CCM are desirable, but can be challenging to negotiate. Many EM‐CCM physicians serve as topic experts in their respective groups for clinical care, quality improvement, education, or research involving the interface between the ED and intensive care unit. As career paths in critical care continue to grow in popularity, EM residents, as well as CCM faculty and program directors, should be aware of the available fellowship options, as well as training and career development needs specific to EM residents.
The Structure of Glycine Dihydrate: Implications for the Crystallization of Glycine from Solution and Its Structure in Outer Space
Authors: Xu Wenqian , Zhu Qiang , Hu Chunhua (Tony)
Published: January 2017

Glycine, the simplest amino acid, is also the most polymorphous. Herein, we report the structure determination of a long unknown phase of glycine, which was first reported by Pyne and Suryanarayanan in 2001. To date, this phase has only been prepared at 208 K as nanocrystals within ice. Through computational crystal‐structure prediction and powder X‐ray diffraction methods, we identified this elusive phase as glycine dihydrate (GDH), representing the first report on the structure of a hydrated glycine structure. The structure of GDH has important implications for the state of glycine in aqueous solution and the mechanisms of glycine crystallization. GDH may also be the form of glycine that comes to Earth from extraterrestrial sources.
Palladium‐Catalyzed Hydrolytic Cleavage of Aromatic C−O Bonds
Authors: Wang Meng , Shi Hui , Camaioni Donald M. , Lercher Johannes A.
Published: January 2017

Metallic palladium surfaces are highly selective in promoting the reductive hydrolysis of aromatic ethers in aqueous phase at relatively mild temperatures and pressures of H2. At quantitative conversions, the selectivity to hydrolysis products of PhOR ethers was observed to range from 50 % (R=Ph) to greater than 90 % (R=n‐C4H9, cyclohexyl, and PhCH2CH2). By analysis of the evolution of products with and without incorporation of H218O, the pathway was concluded to be initiated by palladium metal catalyzed partial hydrogenation of the phenyl group to an enol ether. Water then rapidly adds to the enol ether to form a hemiacetal, which then undergoes elimination to cyclohexanone and phenol/alkanol products. A remarkable feature of the reaction is that the stronger Ph−O bond is cleaved rather than the weaker aliphatic O−R bond.
Discovery of Novel Cinchona‐Alkaloid‐Inspired Oxazatwistane Autophagy Inhibitors
Authors: Laraia Luca , Ohsawa Kosuke , Konstantinidis Georgios , Robke Lucas , Wu Yao‐Wen , Kumar Kamal , Waldmann Herbert
Published: January 2017

The cinchona alkaloids are a privileged class of natural products and are endowed with diverse bioactivities. However, for compounds with the closely‐related oxazatricyclo[4.4.0.0]decane (“oxazatwistane”) scaffold, which are accessible from cinchonidine and quinidine by means of ring distortion and modification, biological activity has not been identified. We report the synthesis of an oxazatwistane compound collection through employing state‐of‐the‐art C−H functionalization, and metal‐catalyzed cross‐coupling reactions as key late diversity‐generating steps. Exploration of oxazatwistane bioactivity in phenotypic assays monitoring different cellular processes revealed a novel class of autophagy inhibitors termed oxautins, which, in contrast to the guiding natural products, selectively inhibit autophagy by inhibiting both autophagosome biogenesis and autophagosome maturation.
A Ternary Solvent Method for Large‐Sized Two‐Dimensional Perovskites
Authors: Chen Junnian , Gan Lin , Zhuge Fuwei , Li Huiqiao , Song Jizhong , Zeng Haibo , Zhai Tianyou
Published: January 2017

Recent reports demonstrate that a two‐dimensional (2D) structural characteristic can endow perovskites with both remarkable photoelectric conversion efficiency and high stability, but the synthesis of ultrathin 2D perovskites with large sizes by facile solution methods is still a challenge. Reported herein is the controlled growth of 2D (C4H9NH3)2PbBr4 perovskites by a chlorobenzene‐dimethylformide‐acetonitrile ternary solvent method. The critical factors, including solvent volume ratio, crystallization temperature, and solvent polarity on the growth dynamics were systematically studied. Under optimum reaction condition, 2D (C4H9NH3)2PbBr4 perovskites, with the largest lateral dimension of up to 40 μm and smallest thickness down to a few nanometers, were fabricated. Furthermore, various iodine doped 2D (C4H9NH3)2PbBrxI4−x perovskites were accessed to tune the optical properties rationally.
A Hollow Spherical Carbon Derived from the Spray Drying of Corncob Lignin for High‐Rate‐Performance Supercapacitors
Authors: Pan Zheng‐Ze , Dong Liubing , Lv Wei , Zheng Dequn , Li Zhengjie , Luo Chong , Zheng Cheng , Yang Quan‐Hong , Kang Feiyu
Published: January 2017

Controlling the microstructure of biomass‐derived carbon is of essential importance for directing its use. Herein, a hollow spherical carbon (HSC) was prepared from corncob lignin through spray drying and subsequent heat treatment. The HSC, which is characterized by its hierarchically porous structure, delivers high rate capability when it is directly used as electrode material for supercapacitors. This strategy that uses lignin as the precursor avoids the intrinsic difficulty in tuning the microstructure of the biomass‐derived carbons and is suitable for mass production for practical use.
Levofloxacin effect on erlotinib absorption. Evaluation of the interaction in undernutrition situations through population pharmacokinetic analysis in rats
Authors: Pérez‐Pitarch Alejandro , Guglieri‐López Beatriz , Nacher Amparo , Merino Virginia , Merino‐Sanjuan Matilde
Published: January 2017

The main objective of this study was to develop a pharmacokinetic model in order to describe the intestinal absorption of erlotinib in rat and to quantify the interaction of levofloxacin on this process in well‐ and under‐nourished rats. Absorption studies were performed in male Wistar rats. Concentration–time profiles in proximal and distal intestine were analysed through non‐linear mixed effect modelling using the NONMEM software version 7.3. Simulations were performed in order to explore the influence of covariates on the apparent absorption rate constant. A passive absorption and an active secretion process best‐described erlotinib absorption from lumen to enterocyte. The developed model indicates that levofloxacin exerts an inhibition on erlotinib efflux transporters of the gut epithelium. Undernourishment proved to significantly decrease the maximum capacity of the secretion process. Simulations evidenced that erlotinib absorption only takes place at high enough drug concentrations to overcome the effect of efflux transporters. On the other hand, when levofloxacin is present in the intestinal lumen of undernourished rats, erlotinib drug absorption takes place even at low erlotinib concentrations. In the clinical setting, this interaction may result in increased exposure to erlotinib, especially in undernourished cancer patients. Copyright © 2017 John Wiley & Sons, Ltd.
Abnormal levels of seven amino neurotransmitters in depressed rat brain and determination by HPLC‐FLD
Authors: Cui Ting , Qiu Hong‐Mei , Huang Dan , Zhou Qi‐Xin , Fu Xiao‐Yan , Li Hai‐Yan , Jiang Xin‐Hui
Published: January 2017

The determination of amino acids with actions like neurotransmitters or modulators has been increasingly important for diagnosis in many neuropsychiatric diseases. A rapid and simple high‐performance liquid chromatography with fluorescence detection method was developed for simultaneous determination of seven amino acids: aspartate (Asp), glutamate (Glu), serine (Ser), glutamine (Gln), glycine (Gly), taurine (Tau) and γ‐aminobutyric` acid (GABA). Homoserine was used as an internal standard. The analysis was performed on a BDS column with methanol and 50 mm sodium acetate solution (pH 6.5) using a simple gradient elution. Several parameters of the developed method were validated including linearity, accuracy, precision, extraction recovery and stability, which were within the acceptable range. The method was successfully applied to determination of real samples: hippocampus and cortex in depressed rats exposed to chronically unpredictable stress in order to study if there existed differences in the seven amino acids levels between depressed rats and control. The results showed that Asp, Gly, Tau and GABA significantly decreased with increasing Gln in the hippocampus of depressed rats, compared with that of the control group, among which obviously lower level of Asp and higher level of Gln in cortex were observed. The analytical method and the results could be useful for clinical diagnosis and further insight into pathophysiological mechanism of depression.
Structural Elucidation of a Nonpeptidic Inhibitor Specific for the Human Immunoproteasome
Authors: Cui Haissi , Baur Regina , Le Chapelain Camille , Dubiella Christian , Heinemeyer Wolfgang , Huber Eva M. , Groll Michael
Published: January 2017

Selective inhibition of the immunoproteasome is a promising approach towards the development of immunomodulatory drugs. Recently, a class of substituted thiazole compounds that combine a nonpeptidic scaffold with the absence of an electrophile was reported in a patent. Here, we investigated the mode of action of the lead compound by using a sophisticated chimeric yeast model of the human immunoproteasome for structural studies. The inhibitor adopts a unique orientation perpendicular to the β5i substrate‐binding channel. Distinct interactions between the inhibitor and the subpockets of the human immunoproteasome account for its isotype selectivity.
Coke‐Tolerant Gadolinium‐Promoted HZSM‐5 Catalyst for Methanol Conversion into Hydrocarbons
Authors: Kim Sungtak , Kim Yong Tae , Hwang Ahron , Jun Ki‐Won , Kwak Geunjae
Published: January 2017

The role of Gd as a coke inhibitor was studied for the methanol‐to‐hydrocarbons reaction. It was revealed that thin films of gadolinium oxide covered the ZSM‐5 crystals and that the Gd atoms that were uniformly dispersed on the surface enhanced the basicity of the parent ZSM‐5. These synergetic effects improved the durability of the acidic function and diminished the growth of coke precursors, which resulted in an increased lifetime of the catalyst.
Biomimetic Activation of Molecular Oxygen with a Combined Metalloporphyrinic Framework and Co‐catalyst Platform
Authors: Zhao Min , Wu Chuan‐De
Published: January 2017

Cytochromes P450 are powerful biocatalysts that present high catalytic efficiency in the aerobic oxidation of hydrocarbons under mild conditions. Even though metal–organic frameworks (MOFs), consisting of biomimetic metalloporphyrin moieties, are highly active in a number of reactions, they are almost powerless in the aerobic oxidation of inert hydrocarbons under mild conditions. Inspired by the catalytic mechanism of enzymes, we introduce N‐hydroxyphthalimide (NHPI) as an assistant catalyst to help metalloporphyrinic MOF catalysis, for which NHPI acts as a proton‐ and electron‐transfer mediator. The coupled biomimetic system is efficient in the aerobic oxidation of arylalkanes under mild conditions. The catalytic efficiency is significantly improved if the [WZn{Co(H2O)}2(ZnW9O34)2]12− polyoxometalate is used as a co‐catalyst. The biomimetic platform exhibits enzyme‐like characters by imitating the structural features, active sites, and catalytic mechanism of enzymes.
Visible Light [2+2] Photocycloaddition Mediated by Flavin Derivative Immobilized on Mesoporous Silica
Authors: Špačková Jessica , Svobodová Eva , Hartman Tomáš , Stibor Ivan , Kopecká Jitka , Cibulková Jana , Chudoba Josef , Cibulka Radek
Published: January 2017

7,8‐Dimethoxy‐3‐methylalloxazine was immobilized on mesoporous silica (MCM‐41) to provide a heterogenized flavin photocatalyst. Thus, the prepared heterogeneous catalyst 2 was found to sensitize the visible light [2+2] cycloaddition of various types of dienes to produce corresponding cyclobutanes in high yields and diastereoselectivities. Use of 2 enables procedures which are advantageous owing to simple operation and workup, no additives required, and minimum waste generation.
Selective Oxidation of n‐Butane and Isobutane Catalyzed by Boron Nitride
Authors: Venegas Juan M. , Grant Joseph T. , McDermott William P. , Burt Samuel P. , Micka Jack , Carrero Carlos A. , Hermans Ive
Published: January 2017

Hexagonal boron nitride (hBN) is presented as an outstanding catalyst for the selective production of C4 olefins by the oxidative dehydrogenation of n‐butane and isobutane. Unlike catalysts reported previously, hBN limits the amount of undesired COx and instead forms C2 and C3 olefins as the main side products. Kinetic experiments suggest a mechanism in which the rates of n‐butane and isobutane consumption are dependent on O2 adsorption. Kinetic and spectroscopic insights are used to formulate mechanistic hypotheses for the formation mechanisms of C2–C4 olefins.
Production of Glucosamine from Chitin by Co‐solvent Promoted Hydrolysis and Deacetylation
Authors: Zhang Jiaguang , Yan Ning
Published: January 2017

Production of renewable chemicals with established market and high value is highly desirable in biomass utilization. Herein, glucosamine, an amino sugar with various applications, was generated in a single step by the acid‐catalyzed transformation of chitin. Aprotic polar solvents were mixed with water to promote the hydrolysis as well as the deacetylation reactions, significantly enhancing product yield and/or reducing the concentration and amount of acid catalyst required. By employing the optimized co‐solvent system, glucosamine was achieved with 80 % yield at 175 °C in 1 h from ball‐milled chitin, in sharp contrast with the pure water system with the same acid concentration in which less than 1 % glucosamine was obtained. Correlations between the promotional effect and various solvent property parameters were discussed and proposed, providing guidance on the choice of solvent for further optimization of the co‐solvent system for similar applications.
Synthesis of a Small Amorphous PdMo/C Nanocatalyst and Pd Nanocubes Enclosed within (100) Planes and Their Use for Ethylene Glycol Electro–oxidation
Authors: Ambriz‐Peláez Oscar , Álvarez‐Contreras Lorena , Guerra‐Balcázar Minerva , Ledesma‐García Janet , Arriaga Luis Gerardo , Arjona Noé
Published: January 2017

In this work, PdMo/C and Pd/C nanocubes were synthesized and used for the electro‐oxidation of ethylene glycol. The XRD patterns revealed that the Pd/C nanocubes had an average crystallite size of 10.9 nm, whereas the PdMo/C nanoparticles were amorphous. HRTEM images indicated the presence of only cubic‐shaped nanoparticles for Pd/C nanocubes and semispherical nanoparticles for PdMo/C with sizes of 9 and 2 nm, respectively. XPS and line‐scan EDX spectroscopy confirmed the presence of Pd and Mo in the PdMo/C nanocatalyst, and Mo was determined to be incorporated with Pd in the form MoO3. The Pd/C nanocubes exhibited a current density that was 9.3 times higher than commercial Pd/C, demonstrating the superior activity of the (100) facet. The combined effects of the amorphous structure and the presence of molybdenum oxides enhanced the activity of PdMo/C, which demonstrated a 1.5‐fold increase current density with respect to the Pd/C nanocubes and a 12‐fold increase compared to commercial Pd/C.
Photoantimicrobial Biohybrids by Supramolecular Immobilization of Cationic Phthalocyanines onto Cellulose Nanocrystals
Authors: Anaya‐Plaza Eduardo , van de Winckel Eveline , Mikkilä Joona , Malho Jani‐Markus , Ikkala Olli , Gulías Oscar , Bresolí‐Obach Roger , Agut Montserrat , Nonell Santi , Torres Tomás , Kostiainen Mauri A. , de la Escosura Andrés
Published: January 2017

The development of photoactive and biocompatible nanostructures is a highly desirable goal to address the current threat of antibiotic resistance. Here, we describe a novel supramolecular biohybrid nanostructure based on the non‐covalent immobilization of cationic zinc phthalocyanine (ZnPc) derivatives onto unmodified cellulose nanocrystals (CNC), following an easy and straightforward protocol, in which binding is driven by electrostatic interactions. These non‐covalent biohybrids show strong photodynamic activity against S. aureus and E. coli, representative examples of Gram‐positive and Gram‐negative bacteria, respectively, and C. albicans, a representative opportunistic fungal pathogen, outperforming the free ZnPc counterparts and related nanosystems in which the photosensitizer is covalently linked to the CNC surface.
Optimization of supercritical fluid extraction of isoflavone from soybean meal
Authors: Lummaetee Kanjana , Ku Hong‐Ming , Wongrat Wongphaka , Elkamel Ali
Published: January 2017

This study aims at developing a mathematical model to predict the yield of isoflavone from soybean meal in a supercritical extraction process using carbon dioxide and aqueous methanol as a co‐solvent and to optimize the process using a genetic algorithm. In the model, a partial differential equation based conservation of mass was solved to predict the yield of isoflavone extraction. The model parameters such as densities of carbon dioxide and co‐solvent methanol, the mixture viscosity, the binary diffusion coefficient of isoflavone in the supercritical solvents, the film mass transfer coefficient, effective diffusivity, and axial dispersion coefficient were estimated using available correlations, and the solubility was estimated using the Mohsen‐Nia‐Moddaress‐Mansoori equation of state. The model was successfully validated with experimental data. In the optimization, the operating conditions of the isoflavone extraction process were identified as decision variables and a profit function was maximized. The optimum was found under the condition in which the carbon dioxide flow rate was 5.88 kg/h and the particle diameter was 0.68 mm, when the temperature was 323.15 K, the pressure was 59.45 MPa, and the extraction time was 283 min. The maximum profit found under these optimum conditions was 46.18 $ per batch.
Old Drug Scaffold, New Activity: Thalidomide‐Correlated Compounds Exert Different Effects on Breast Cancer Cell Growth and Progression
Authors: Iacopetta Domenico , Carocci Alessia , Sinicropi Maria Stefania , Catalano Alessia , Lentini Giovanni , Ceramella Jessica , Curcio Rosita , Caroleo Maria Cristina
Published: January 2017

Thalidomide was first used for relief of morning sickness in pregnant women and then withdrawn from the market because of its dramatic effects on normal fetal development. Over the last decades, it has been used successfully for the treatment of several pathologies, including cancer. Many analogues with improved activity have been synthesized and tested. Herein we report some effects on the growth and progression of MCF‐7 and MDA‐MB‐231 breast cancer cells by a small series of thalidomide‐correlated compounds, which are very effective at inducing cancer cell death by triggering TNFα‐mediated apoptosis. The most active compounds are able to drastically reduce the migration of breast cancer cells by regulation of the two major proteins involved in epithelial–mesenchymal transition (EMT): vimentin and E‐cadherin. Moreover, these compounds diminish the intracellular biosynthesis of vascular endothelial growth factor (VEGF), which is primarily involved in the promotion of angiogenesis, sustaining tumor progression. The multiple features of these compounds that act on various key points of the tumorigenesis process make them good candidates for preclinical studies.
Method for the unique identification of hyperelastic material properties using full‐field measures. Application to the passive myocardium material response
Authors: Perotti Luigi E. , Ponnaluri Aditya V. S. , Krishnamoorthi Shankarjee , Balzani Daniel , Ennis Daniel B. , Klug William S.
Published: January 2017

Quantitative measurement of the material properties (eg, stiffness) of biological tissues is poised to become a powerful diagnostic tool. There are currently several methods in the literature to estimating material stiffness, and we extend this work by formulating a framework that leads to uniquely identified material properties. We design an approach to work with full‐field displacement data—ie, we assume the displacement field due to the applied forces is known both on the boundaries and also within the interior of the body of interest—and seek stiffness parameters that lead to balanced internal and external forces in a model. For in vivo applications, the displacement data can be acquired clinically using magnetic resonance imaging while the forces may be computed from pressure measurements, eg, through catheterization. We outline a set of conditions under which the least‐square force error objective function is convex, yielding uniquely identified material properties. An important component of our framework is a new numerical strategy to formulate polyconvex material energy laws that are linear in the material properties and provide one optimal description of the available experimental data. An outcome of our approach is the analysis of the reliability of the identified material properties, even for material laws that do not admit unique property identification. Lastly, we evaluate our approach using passive myocardium experimental data at the material point and show its application to identifying myocardial stiffness with an in silico experiment modeling the passive filling of the left ventricle.
Facile Morphology‐Controlled Synthesis of Organolead Iodide Perovskite Nanocrystals Using Binary Capping Agents
Authors: Debroye Elke , Yuan Haifeng , Bladt Eva , Baekelant Wouter , Van der Auweraer Mark , Hofkens Johan , Bals Sara , Roeffaers Maarten B. J.
Published: January 2017

Controlling the morphology of organolead halide perovskite crystals is crucial to a fundamental understanding of the materials and to tune their properties for device applications. Here, we report a facile solution‐based method for morphology‐controlled synthesis of rod‐like and plate‐like organolead halide perovskite nanocrystals using binary capping agents. The morphology control is likely due to an interplay between surface binding kinetics of the two capping agents at different crystal facets. By high‐resolution scanning transmission electron microscopy, we show that the obtained nanocrystals are monocrystalline. Moreover, long photoluminescence decay times of the nanocrystals indicate long charge diffusion lengths and low trap/defect densities. Our results pave the way for large‐scale solution synthesis of organolead halide perovskite nanocrystals with controlled morphology for future device applications.
European Banks' Reputation for Corporate Social Responsibility
Authors: Forcadell Francisco Javier , Aracil Elisa
Published: January 2017

Dow Jones Sustainability Index (DJSI) members are considered top sustainable companies within each sector. Thus, DJSI inclusion signals a reputation for strong Corporate Social Responsibility (CSR) engagement, which should contribute to enhanced firm performance. This paper examines the performance of the European banks listed in the DJSI for the period 2003–2013 and analyzes the effect of having a reputation for CSR on performance during a period of economic crisis. A vast amount of literature links CSR, reputation and performance, but few studies have examined the banking sector and the impact of the last recession. Our results suggest that banks' efforts to build a reputation for CSR benefits performance. Nevertheless, in periods of crisis, these efforts do not contribute to improved returns. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Authorship verification using deep belief network systems
Authors: Brocardo Marcelo Luiz , Traore Issa , Woungang Isaac , Obaidat Mohammad S.
Published: January 2017

This paper explores the use of deep belief networks for authorship verification model applicable for continuous authentication (CA). The proposed approach uses Gaussian units in the visible layer to model real‐valued data on the basis of a Gaussian‐Bernoulli deep belief network. The lexical, syntactic, and application‐specific features are explored, leading to the proposal of a method to merge a pair of features into a single one. The CA is simulated by decomposing an online document into a sequence of short texts over which the CA decisions happen. The experimental evaluation of the proposed method uses block sizes of 140, 280, 500 characters, on the basis of the Twitter and Enron e‐mail corpuses. Promising results are obtained, which consist of an equal error rate varying from 8.21% to 16.73%. Using relatively smaller forgery samples, an equal error rate varying from 5.48% to 12.3% is also obtained for different block sizes.
Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives
Authors: Qiu Hongyu , Novikov Aleksandra , Vallon Volker
Published: January 2017

Inhibitors of the sodium‐glucose cotransporter SGLT2 are a new class of antihyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk. However, a potential side effect that has been reported with SGLT2 inhibitors in patients with T2DM and particularly during off‐label use in patients with type 1 diabetes is diabetic ketoacidosis. The US Food and Drug Administration recently warned that SGLT2 inhibitors may result in euglycemic ketoacidosis. Here, we review the basic metabolism of ketone bodies, the triggers of diabetic ketoacidosis, and potential mechanisms by which SGLT2 inhibitors may facilitate the development of ketosis or ketoacidosis. This provides the rationale for measures to lower the risk. We discuss the role of the kidney and potential links to renal gluconeogenesis and uric acid handling. Moreover, we outline potential beneficial effects of modestly elevated ketone body levels on organ function that may have therapeutic relevance for the observed beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system.
Targeted integration of genes in Xenopus tropicalis
Authors: Shi Zhaoying , Tian Dandan , Xin Huhu , Lian Jingru , Guo Xiaogang , Chen Yonglong
Published: January 2017

With the successful establishment of both targeted gene disruption and integration methods in the true diploid frog Xenopus tropicalis, this excellent vertebrate genetic model now is making a unique contribution to modelling human diseases. Here, we summarize our efforts on establishing homologous recombination‐mediated targeted integration in Xenopus tropicalis, the usefulness, and limitation of targeted integration via the homology‐independent strategy, and future directions on how to further improve targeted gene integration in Xenopus tropicalis.
Evaluating the responses of forest ecosystems to climate change and CO2 using dynamic global vegetation models
Authors: Song Xiang , Zeng Xiaodong
Published: January 2017

The climate has important influences on the distribution and structure of forest ecosystems, which may lead to vital feedback to climate change. However, much of the existing work focuses on the changes in carbon fluxes or water cycles due to climate change and/or atmospheric CO2, and few studies have considered how and to what extent climate change and CO2 influence the ecosystem structure (e.g., fractional coverage change) and the changes in the responses of ecosystems with different characteristics. In this work, two dynamic global vegetation models (DGVMs): IAP‐DGVM coupled with CLM3 and CLM4‐CNDV, were used to investigate the response of the forest ecosystem structure to changes in climate (temperature and precipitation) and CO2 concentration. In the temperature sensitivity tests, warming reduced the global area‐averaged ecosystem gross primary production in the two models, which decreased global forest area. Furthermore, the changes in tree fractional coverage (ΔFtree; %) from the two models were sensitive to the regional temperature and ecosystem structure, i.e., the mean annual temperature (MAT; °C) largely determined whether ΔFtree was positive or negative, while the tree fractional coverage (Ftree; %) played a decisive role in the amplitude of ΔFtree around the globe, and the dependence was more remarkable in IAP‐DGVM. In cases with precipitation change, Ftree had a uniformly positive relationship with precipitation, especially in the transition zones of forests (30% < Ftree < 60%) for IAP‐DGVM and in semiarid and arid regions for CLM4‐CNDV. Moreover, ΔFtree had a stronger dependence on Ftree than on the mean annual precipitation (MAP; mm/year). It was also demonstrated that both models captured the fertilization effects of the CO2 concentration.
The effect of tree genetic diversity on insect herbivory varies with insect abundance
Authors: Fernandez‐Conradi Pilar , Jactel Hervé , Hampe Arndt , Leiva Maria José , Castagneyrol Bastien
Published: January 2017

Variance in edibility among plant genotypes is expected to be a key driver of plant genetic diversity (PGD) effects on abundance of insect herbivores and resulting herbivory. Yet, herbivore foraging behavior and leaf consumption may be also context‐dependent and, in particular, influenced by herbivore density, which remains unexplored. We used a combination of field and laboratory experiments with saplings from four half‐sib families (henceforth, families) of pedunculate oak (Quercus robur) to test how PGD and herbivore density interactively affect herbivory. Insect herbivory was assessed in a common garden experiment with plots containing all possible combinations of individuals from one to four oak families. Herbivore density was manipulated by spraying insecticide in a factorial design. Complementary feeding trials with gypsy moth larvae (Lymantria dispar) were used to further explore the mechanisms underlying observed patterns in the field. Herbivory decreased with increasing PGD under normal herbivore density, but not under reduced herbivore abundance. The most damaged oak family in the field was also the most consumed in non‐choice tests and was consistently preferred over other families in choice tests. Trials showed that the presence of less edible families in the diet reduced overall consumption by gypsy moth larvae. Under field conditions, the most edible family consistently benefited most from being associated with less edible, neighboring genotypes. Our results demonstrate that small‐scale PGD can provide associational resistance to insect herbivory, probably through change in herbivore foraging activity. Importantly, they also reveal that the magnitude of genetic diversity effect depends on herbivore density.
Ring‐Opening Reaction of Imidazo[1,2‐a]pyridines Using (Diacetoxyiodo)benzene and NaN3: The Synthesis of α‐Iminonitriles
Authors: Kalbandhe Amit H. , Kavale Ashish C. , Karade Nandkishor N.
Published: January 2017

The reaction of imidazo[1,2‐a]pyridine with NaN3 in the presence of (diacetoxyiodo)benzene as an oxidant resulted in the unusual formation of α‐iminonitriles in good yields under mild conditions. This method provides access to α‐iminonitriles under cyanide‐free and metal‐free reaction conditions.
Voltammetric Separation and Determination of Glutathione and L‐tyrosine with Chlorogenic Acid as an Electrocatalytic Mediator
Authors: Huang Ying , Chen Mei , Li Xiaofeng , Zhang Cuiyun
Published: January 2017

A novel and sensitive voltammetric method was proposed for separation and determination of glutathione (GSH) and L‐tyrosine (Tyr) at acetylene black and chitosan modified glassy carbon electrode (AB‐CS/GCE). By introducing chlorogenic acid (CGA) as a new electrocatalytic mediator, GSH could be detected at much lower potential with symmetric peak shape. Acetylene black and chitosan composite served as current signal amplifier for sensitive detection. The electrochemical behavior of GSH and Tyr in the presence of CGA was studied at AB‐CS/GCE and complete separation of anodic peaks was achieved. Under the optimum conditions, the electrocatalytic oxidation peak current of GSH showed a linear dependence on its concentration in the ranges of 2.0×10−7‐4.0×10−5 M with the detection limit of 5.8×10−8 M (S/N=3), while the oxidation peak current of Tyr was linear to its concentration from 2.5×10−6 to 4.3×10−4 M with the detection limit of 9.2×10−7 M (S/N=3) by differential pulse voltammetry (DPV). The established method has been applied to the simultaneous determination of GSH and Tyr in human urine with satisfactory results.
Comparative Study on Electroanalysis of Fenthion Using Silver Amalgam Film Electrode and Glassy Carbon Electrode Modified with Reduced Graphene Oxide
Authors: Smarzewska Sylwia , Metelka Radovan , Festinger Natalia , Guziejewski Dariusz , Ciesielski Witold
Published: January 2017

Oxidation and reduction processes of the insecticide fenthion was comparatively investigated at a reduced graphene oxide modified glassy carbon electrode (RGO‐GCE) and a cyclic renewable silver amalgam film electrode (Hg(Ag)FE) using square wave stripping voltammetry (SWSV). The influence of pH and SW parameters was investigated. The linear concentration ranges were found to be 1 × 10−6 – 2 × 10−5 and 1 × 10−7 – 2 × 10−5 mol L−1 for Hg(Ag)FE and RGO‐GCE, respectively. The detection and quantification limits were calculated as 1.3 × 10−7 and 4.5 × 10−7 mol L−1 for Hg(Ag)FE and 7.6 × 10−9 and 2.5 × 10−8 mol L−1 for RGO‐GCE. Both of the developed electroanalytical methods offer rapid and simple detection of fenthion and were used on spiked tap and river water and apple juice samples. Scanning electron microscopy was used for RGO‐GCE surface characterization.
Comparative study on structural properties and combustion kinetics of Chinese Shenhua long flame raw coal and its pyrolytic char
Authors: Wang Yunfei , Song Yinmin , Zhou Huacong , Zhi Keduan , Teng Yingyue , He Runxia , Tian Rongkai , Liu Quansheng
Published: January 2017

Research on the structural and combustion properties of coal is of great importance for its conversion and applications in view of fundamental studies. In this work, we conducted the first detailed study on the structural properties and combustion kinetics of Chinese Shenhua raw coal (RC) and its pyrolytic char (PC). The combustion kinetics was simulated by using the random pore model (RPM). The results showed that RC and PC were composed of both a plant‐cell‐like structure and a discrete particulate structure. In addition, PC had a larger specific surface area, finer particles, higher aromaticity, and higher degree of aromatic ring condensation than those of RC. Combustion of PC showed higher ignition temperature, lower burnout temperature, and a higher combustion index compared to RC. A high correlation coefficient R2 (0.999) and a low average error θ (0.008) were obtained using the RPM. The combustion apparent activation energy E and the structural parameter ψ of RC were 40.30 kJ mol−1 and 0.53, respectively. For PC, the values of E and ψ were estimated to be 60.01 kJ mol−1 and 0, respectively. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 766–774, 2017
Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review
Authors: Ajmera Veeral H. , Terrault Norah A. , Harrison Stephen A.
Published: January 2017

Moderate alcohol consumption in patients with nonalcoholic fatty liver disease (NAFLD) is common, yet the effects on cardiovascular and liver health are unclear. Moderate alcohol use is associated with improved insulin sensitivity and decreased cardiovascular mortality in the general population, but whether similar benefits would be observed in persons with NAFLD remains largely unstudied. There is significant overlap in the pathogenesis of alcoholic liver disease (ALD) and NAFLD, although studies of ALD have focused on pathological alcohol intake and few mechanistic studies of moderate alcohol use in NAFLD exist. We undertook a critical review of the effect of moderate alcohol use on cardiovascular and liver disease in patients with NAFLD. A total of seven observational studies met the criteria for inclusion (one for cardiovascular endpoints and six for liver endpoints). Insufficient studies have assessed the association of moderate alcohol use with cardiovascular outcomes. There was a positive association between moderate alcohol use and decreased NASH and fibrosis; however, heavy episodic drinking may accelerate fibrosis progression and moderate alcohol use may increase the risk of hepatocellular carcinoma in patients with advanced fibrosis. Significant methodological limitations were present, including incomplete adjustment for confounding factors and failure to measure lifetime use or the pattern of alcohol intake. Thus, a strong recommendation of benefit of moderate alcohol use in NAFLD cannot be made. There remains a need for additional high‐quality longitudinal studies that evaluate both cardiovascular and liver outcomes among NAFLD patients with moderate or lesser degrees of alcohol use. (Hepatology 2017;65:2090‐2099).
Retrospective cohort study of prophylactic intraoperative uterine artery embolization for abnormally invasive placenta
Authors: Pan Yi , Zhou Xin , Yang Zhengqiang , Cui Shudong , De Wei , Sun Lizhou
Published: January 2017

Objective

To evaluate the safety and efficacy of prophylactic intraoperative uterine artery embolization (UAE) during cesarean delivery as conservative treatment for patients with abnormally invasive placenta.

Methods

A retrospective cohort study enrolled patients surgically diagnosed with abnormally invasive placenta who underwent cesarean delivery at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, between February 1, 2012, and February 28, 2015. Postpartum estimated blood loss, blood transfusions, hysterectomy, and adverse events were compared between patients who underwent cesarean delivery only (control group) and those who underwent concurrent prophylactic intraoperative UAE (UAE group).

Results

There were 45 patients included in the study; 26 and 19 in the UAE and control groups, respectively. Among patients who did not undergo hysterectomy owing to placenta accreta, the mean estimated blood loss was lower among patients in the UAE group (P=0.005); however, among patients who did undergo hysterectomy for placenta increta or percreta, no difference in mean estimated blood loss was observed (P=0.973). There were no differences in the hysterectomy rate (P=0.639) or incidence of requiring massive blood transfusion (P=0.050) between the groups. Only one patient in the UAE group experienced uterine necrosis.

Conclusion

Prophylactic intraoperative UAE was relatively safe and effective for reducing postpartum hemorrhage among patients with placenta accreta. The potential benefits could be lower among patients with placenta increta or percreta.