bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug‐Loaded Magnetic Solid Lipid Nanoparticles
Authors: Grillone Agostina , Riva Eugenio Redolfi , Mondini Alessio , Forte Claudia , Calucci Lucia , Innocenti Claudia , de Julian Fernandez Cesar , Cappello Valentina , Gemmi Mauro , Moscato Stefania , Ronca Francesca , Sacco Rodolfo , Mattoli Virgilio , Ciofani Gianni
Published: June 2015

Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib‐loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues. Sorafenib and superparamagnetic iron oxide nanoparticles are encapsulated in solid lipid nanoparticles by a hot homogenization technique using cetyl palmitate as lipid matrix. The obtained nanoparticles (Sor‐Mag‐SLNs) have a sorafenib loading efficiency of about 90% and are found to be very stable in an aqueous environment. Plain Mag‐SLNs exhibit good cytocompatibility, whereas an antiproliferative effect against tumor cells (human hepatocarcinoma HepG2) is observed for drug‐loaded Sor‐Mag‐SLNs. The obtained results show that it is possible to prepare stable Sor‐Mag‐SLNs able to inhibit cancer cell proliferation through the sorafenib cytotoxic action, and to enhance/localize this effect in a desired area thanks to a magnetically driven accumulation of the drug. Moreover, the relaxivity properties observed in water suspensions hold promise for Sor‐Mag‐SLN tracking through clinical magnetic resonance imaging.
Back to Basics: Moscow Rules!
Authors: Creo Robert A.
Published: June 2015

Editor's note: Longtime Alternatives columnist Bob Creo, a veteran Pittsburgh neutral, is revisiting his classic CPR Institute website columns of a decade ago in a Back to Basics Series that he has subtitled “Human Problems, Human Solutions.” In his more‐recent Master Mediator columns, Creo has focused on neuroscience, psychological factors and cognitive biases that affect dispute resolution. These updated Back to Basics columns, in print for the first time, began in November, revisiting mediation‐room techniques and practice issues. This month, the focus is on.
A Single‐Step Synthesis of Electroactive Mesoporous ProDOT‐Silica Structures
Authors: Kim Jeonghun , Kim Byeonggwan , Anand Chokkalingam , Mano Ajayan , Zaidi Javaid S. M. , Ariga Katsuhiko , You Jungmok , Vinu Ajayan , Kim Eunkyoung
Published: June 2015

The single‐step preparation of highly ordered mesoporous silica hybrid nanocomposites with conjugated polymers was explored using a novel cationic 3,4‐propylenedioxythiophene (ProDOT) surfactant (PrS). The method does not require high‐temperature calcination or a washing procedure. The combination of self‐assembly of the silica surfactant and in situ polymerization of the ProDOT tail is responsible for creation of the mesoporosity with ultralarge pores, large pore volume, and electroactivity. As this novel material exhibits excellent textural parameters together with electrical conductivity, we believe that this could find potential applications in various fields. This novel concept of creating mesoporosity without a calcination process is a significant breakthrough in the field of mesoporous materials and the method can be further generalized as a rational preparation of various mesoporous hybrid materials having different structures and pore diameters.
Total Synthesis of Limonin
Authors: Yamashita Shuji , Naruko Akito , Nakazawa Yuki , Zhao Le , Hayashi Yujiro , Hirama Masahiro
Published: June 2015

Limonoids are highly oxygenated C13α‐triterpenes and common secondary metabolites. Several hundred congeners have been isolated to date. The first total synthesis of (±)‐limonin, the flagship congener of the limonoids, is now reported and features 1) a tandem radical cyclization generating the BCD ring system with the C13α configuration that is essential to the limonoids and a Robinson annulation to construct the limonoid androstane framework, 2) a singlet‐oxygen cycloaddition and a Baeyer–Villiger oxidation to synthesize the highly oxidized D ring, and 3) a Suárez reaction to construct the unique AA′ ring system.
Enhanced Raman Scattering from Vibro‐Polariton Hybrid States
Authors: Shalabney Atef , George Jino , Hiura Hidefumi , Hutchison James A. , Genet Cyriaque , Hellwig Petra , Ebbesen Thomas W.
Published: June 2015

Ground‐state molecular vibrations can be hybridized through strong coupling with the vacuum field of a cavity optical mode in the infrared region, leading to the formation of two new coherent vibro‐polariton states. The spontaneous Raman scattering from such hybridized light–matter states was studied, showing that the collective Rabi splitting occurs at the level of a single selected bond. Moreover, the coherent nature of the vibro‐polariton states boosts the Raman scattering cross‐section by two to three orders of magnitude, revealing a new enhancement mechanism as a result of vibrational strong coupling. This observation has fundamental consequences for the understanding of light‐molecule strong coupling and for molecular science.
Preparation and properties of a novel flame retardant polyurethane quasi‐prepolymer for toughening phenolic foam
Authors: Ding Haiyang , Wang Jifu , Liu Juan , Xu Yuzhi , Chen Riqing , Wang Chunpeng , Chu Fuxiang
Published: June 2015

A novel phosphorus‐ and nitrogen‐containing polyurethane quasi‐prepolymer (PNPUQP) was synthesized and incorporated into phenolic foam (PF) in different ratios in order to improve the toughness. The structure of PNPUQP was confirmed by Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR). The effects of PNPUQP on the flame retardant properties, thermal stability and mechanical properties of modified PF were investigated. The results suggested that the addition of 3 wt % PNPUQP increased the toughness of PF and improved the flame retardancy. The investigation on the morphology of PF and modified PF by scanning electron microscope (SEM) certified the good toughness of the PNPUQP on PF. Additionally, the thermal properties of the foams were investigated by thermogravimetric analysis (TGA) under N2 atmosphere. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42424.
Compatibility and nonlinear viscoelasticity of polychloroprene/polyvinyl chloride blends with nitrile butadiene rubber as a compatibilizer
Authors: Jiang Guiyang , Feng Chi , Zhang Hongmei , Zhang Yong , Yamagishi Uichiro , Toya Hideki , Fujii Nobuhiko
Published: June 2015

Miscible polychloroprene/polyvinyl chloride (CR/PVC) blends with nitrile butadiene rubber (NBR) as a compatibilizer were prepared. The effect of NBR on the compatibility between CR and PVC was mainly analyzed by studying the thermal behavior and the phase structure of CR/PVC blends. An obvious decrement in the Tg of PVC phase successfully provided an explanation for the compatibilization of NBR. Due to the improved compatibility between CR and PVC, the size of PVC particles in CR/PVC blends decreased a lot according to the scanning electronic microscopic images. The significant improvement of mechanical properties of CR/PVC blends was in good agreement with the better compatibility between CR and PVC phases. The softening effect of NBR on the nonlinear viscoelasticity of CR/PVC blends was also studied by RPA 2000. Temperature sweep test by RPA 2000, a less reported characterization method of Tg, was successfully applied to measure Tg of CR/PVC blends and study the compatibilization of NBR. The reason for better thermal stability and the thermal decomposition mechanism of CR/PVC blends were analyzed according to the results of TGA. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42448.
Synthesis and application of a natural plasticizer based on cardanol for poly(vinyl chloride)
Authors: Chen Jie , Liu Zengshe , Li Ke , Huang Jinrui , Nie Xiaoan , Zhou Yonghong
Published: June 2015

A natural plasticizer with multifunctional groups, similar in structure to phthalates, cardanol derivatives glycidyl ether (CGE) was synthesized from cardanol by a two‐step modification process and characterized by FT‐IR, 1HNMR, and 13CNMR. The resulting product was incorporated to PVC (CGE/PVC), and plasticizing effect was compared with PVC incorporated with two kinds of commercial phthalate ester plasticizers bis (2‐ethylhexyl) benzene‐1,4‐dicarboxylate (DOTP) and diisononyl phthalate (DINP). Dynamic mechanical analysis and mechanical properties testing of the plasticized PVC samples were performed in order to evaluate their flexibility, compatibility, and plasticizing efficiency. SEM was employed to produce fractured surface morphology. Thermogravimetric analysis and discoloration tests were used to characterize the thermal stabilities. Dynamic stability analysis was used to test the processability of formulations. Compared with DOTP and DINP plasticized samples, CGE/PVC has a maximum decrease of 9.27% in glass transition temperature (Tg), a maximum increase of 17.6% in the elongation at break, and a maximum increase of 31.59°C and 25.31 min in 50% weight loss (T50) and dynamic stability time, respectively. The obtained CGE also has slightly lower volatility resistance and higher exudation resistance than that of DOTP and DINP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42465.
N‐halamine‐modified polyglycolide (PGA) multifilament as a potential bactericidal surgical suture: In vitro study
Authors: Umair Malik Muhammad , Jiang Zhiming , Safdar Waseem , Xie Zhiwei , Ren Xuehong
Published: June 2015

In this study, new cationic homopolymer and anionic copolymer were synthesized, and deposited onto polyglycolide sutures using a layer‐by‐layer assembly technique. The coated sutures were rendered antibacterial by chlorinating with dilute solution of household bleach solution at pH 7. The chlorination treatment transformed the NH groups of anionic copolymer into N‐halamine structures. The N‐halamine‐modified sutures were challenged with Staphylococcus aureus and Escherichia coli O157:H7 bacteria at different contact times. The suture with chlorine loading of 0.22% completely inactivated both bacterial strains in 30 min contact time. Fourier transform infrared spectroscopy, scanning electron microscopy, and analytical titration confirmed the successful deposition of the N‐halamine multilayers. The effect of layer‐by‐layer coatings of polyelectrolytes on the chlorine loading and antibacterial efficacy of sutures was evaluated. The straight‐pull and knot‐pull strength tests performed on the sutures reported slight decline in tensile properties after chlorination treatment. The in vitro hemolysis and cytocompatibility tests revealed that the N‐halamines‐based antibacterial sutures were biocompatible. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42483.
Effect of amphiphilic compatibilizers on the filler dispersion and properties of polyethylene—thermally reduced graphene nanocomposites
Authors: Mittal Vikas , Chaudhry Ali U.
Published: June 2015

Compatibilizers of different chemical structures and specifications were used to enhance the filler exfoliation in nanocomposites of polyethylene and thermally reduced graphene prepared by melt mixing route. The mechanical performance of the compatibilized nanocomposites was observed to be better than PE/G nanocomposites due to enhanced extent of filler exfoliation and distribution. Highest increase of 45% in tensile modulus and 13% in peak stress was observed in the composites. Overall, from the mechanical, rheological, thermal, and calorimetric properties, the compatibilizers with best performance were ethylene acrylic acid (EAA) copolymer and chlorinated polyethylene (CPE25). Furthermore, the extent of filler exfoliation was observed to increase with increasing EAA content thus confirming positive interactions between EAA and thermally reduced graphene, though no specific chemical interactions could be detected. The composite properties were observed to reach maximum around 7.5 wt % EAA content, followed by reduced performance due to extensive matrix plasticization. The observed behaviors were a result of interplay of opposing factors like filler exfoliation due to compatibilizer addition and matrix plasticization due to its lower molecular weight, thus the observed optimum comaptibilizer amount was specific to the compatibilizer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 42484.
Chitosan/silk fibroin composite scaffolds for wound dressing
Authors: Guang Shanyi , An Yang , Ke Fuyou , Zhao Dongmei , Shen Yuhua , Xu Hongyao
Published: June 2015

Three‐dimensional (3D) chitosan/silk fibroin (CS/SF) porous composite scaffolds have been prepared by simply coating a thin layer of CS onto spunlaced SF scaffolds via hydrogen‐bonding assembly technique, and they were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X‐ray diffraction (XRD), and mechanical property measurements. The results show that porous scaffolds have a pore diameter around 50–200 μm, and improved mechanical property compared with SF, resulting from strong intermolecular hydrogen bonding interactions between CS and SF, together with the maintained β‐sheet structure of SF. The medical and biological properties of the composite scaffolds were further evaluated. The results demonstrate that they possess good biocompatibility and a broad spectrum of antimicrobial properties. The in vivo animal experiments show that the composite scaffolds promote skin regeneration of rats without any teratogenic effect and inflection, thus they are very promising in the application of wound dressings. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42503.
Student perceptions of independent versus facilitated small group learning approaches to compressed medical anatomy education
Authors: Whelan Alexander , Leddy John J. , Mindra Sean , Matthew Hughes J.D. , El‐Bialy Safaa , Ramnanan Christopher J.
Published: June 2015

The purpose of this study was to compare student perceptions regarding two, small group learning approaches to compressed (46.5 prosection‐based laboratory hours), integrated anatomy education at the University of Ottawa medical program. In the facilitated active learning (FAL) approach, tutors engage students and are expected to enable and balance both active learning and progression through laboratory objectives. In contrast, the emphasized independent learning (EIL) approach stresses elements from the “flipped classroom” educational model: prelaboratory preparation, independent laboratory learning, and limited tutor involvement. Quantitative (Likert‐style questions) and qualitative data (independent thematic analysis of open‐ended commentary) from a survey of students who had completed the preclerkship curriculum identified strengths from the EIL (promoting student collaboration and communication) and FAL (successful progression through objectives) approaches. However, EIL led to student frustration related to a lack of direction and impaired completion of objectives, whereas active learning opportunities in FAL were highly variable and dependent on tutor teaching style. A “hidden curriculum” was also identified, where students (particularly EIL and clerkship students) commonly compared their compressed anatomy education or their anatomy learning environment with other approaches. Finally, while both groups highly regarded the efficiency of prosection‐based learning and expressed value for cadaveric‐based learning, student commentary noted that the lack of grade value dedicated to anatomy assessment limited student accountability. This study revealed critical insights into small group learning in compressed anatomy education, including the need to balance student active learning opportunities with appropriate direction and feedback (including assessment). Anat Sci Educ. © 2015 American Association of Anatomists.
Molecular cloning and promoter analysis of the specific salicylic acid biosynthetic pathway gene phenylalanine ammonia‐lyase (AaPAL1) fromArtemisia annua
Authors: Zhang Ying , Fu Xueqing , Hao Xiaolong , Zhang Lida , Wang Luyao , Qian Hongmei , Zhao Jingya
Published: June 2015

Phenylalanine ammonia‐lyase (PAL) is the key enzyme in the biosynthetic pathway of salicylic acid (SA). In this study, a full‐length cDNA of PAL gene (named asAaPAL1) was cloned fromArtemisia annua. The gene contains an open reading frame of 2,151 bps encoding 716 amino acids. Comparative and bioinformatics analysis revealed that the polypeptide protein ofAaPAL1was highly homologous to PALs from other plant species. Southern blot analysis revealed that it belonged to a gene family with three members. Quantitative RT‐PCR analysis of various tissues ofA. annuashowed thatAaPAL1transcript levels were highest in the young leaves. A 1160‐bp promoter region was also isolated resulting in identification of distinctcis‐regulatory elements including W‐box, TGACG‐motif, and TC‐rich repeats. Quantitative RT‐PCR indicated thatAaPAL1was upregulated by salinity, drought, wounding, and SA stresses, which were corroborated positively with the identifiedcis‐elements within the promoter region.AaPAL1was successfully expressed inEscherichia. coliand the enzyme activity of the purified AaPAL1 was approximately 287.2 U/mg. These results substantiated the involvement ofAaPAL1in the phenylalanine pathway.
Neural crest derivatives in ocular development: Discerning the eye of the storm
Authors: Williams Antionette L. , Bohnsack Brenda L.
Published: June 2015

Neural crest cells (NCCs) are vertebrate‐specific transient, multipotent, migratory stem cells that play a crucial role in many aspects of embryonic development. These cells emerge from the dorsal neural tube and subsequently migrate to different regions of the body, contributing to the formation of diverse cell lineages and structures, including much of the peripheral nervous system, craniofacial skeleton, smooth muscle, skin pigmentation, and multiple ocular and periocular structures. Indeed, abnormalities in neural crest development cause craniofacial defects and ocular anomalies, such as Axenfeld‐Rieger syndrome and primary congenital glaucoma. Thus, understanding the molecular regulation of neural crest development is important to enhance our knowledge of the basis for congenital eye diseases, reflecting the contributions of these progenitors to multiple cell lineages. Particularly, understanding the underpinnings of neural crest formation will help to discern the complexities of eye development, as these NCCs are involved in every aspect of this process. In this review, we summarize the role of ocular NCCs in eye development, particularly focusing on congenital eye diseases associated with anterior segment defects and the interplay between three prominent molecules, PITX2, CYP1B1, and retinoic acid, which act in concert to specify a population of neural crest‐derived mesenchymal progenitors for migration and differentiation, to give rise to distinct anterior segment tissues. We also describe recent findings implicating this stem cell population in ocular coloboma formation, and introduce recent evidence suggesting the involvement of NCCs in optic fissure closure and vascular development. Birth Defects Research (Part C) 105:87–95, 2015. © 2015 Wiley Periodicals, Inc.
Thalidomide‐induced teratogenesis: History and mechanisms
Authors: Vargesson Neil
Published: June 2015

Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man‐made medical disaster ever, where over 10,000 children were born with a range of severe and debilitating malformations. Despite this, the drug is now used successfully to treat a range of adult conditions, including multiple myeloma and complications of leprosy. Tragically, a new generation of thalidomide damaged children has been identified in Brazil. Yet, how thalidomide caused its devastating effects in the forming embryo remains unclear. However, studies in the past few years have greatly enhanced our understanding of the molecular mechanisms the drug. This review will look at the history of the drug, and the range and type of damage the drug caused, and outline the mechanisms of action the drug uses including recent molecular advances and new findings. Some of the remaining challenges facing thalidomide biologists are also discussed. Birth Defects Research (Part C) 105:140–156, 2015. © 2015 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.
Erythropoietin produced by genetic‐modified NIH/3T3 fibroblasts enhances the survival of degenerating neurons
Authors: Li Yi‐Chin , Chen Shiu‐Jau , Chien Chung‐Liang
Published: June 2015

Background

Erythropoietin (EPO) has potent neuroprotective effects. The short‐term delivery of high‐dose EPO seemed to improve patients’ neuromuscular functions; however, excessive EPO resulted in systematically high hematocrit and thrombotic risk. In our study, we established a cellular material for future in vivo studies of neurodegenerative diseases based on EPO provided regionally at a nontoxic level.

Methods

A mouse EPO cDNA was subcloned into the pCMS‐EGFP vector and transfected into NIH/3T3 fibroblasts to design a biological provider that can regionally release EPO for the treatment of neurological diseases. After G418 selection, a stable EPO‐overexpressing cell line, EPO‐3T3‐EGFP, was established. To further confirm the neuroprotective abilities of secreted EPO from EPO‐3T3‐EGFP cells, a cell model of neurodegeneration, PC12‐INT‐EGFP, was applied.

Results

The expression level of EPO was highly elevated in EPO‐3T3‐EGFP cells, and an abundant amount of EPO secreted from EPO‐3T3‐EGFP cells was detected in the extracellular milieu. After supplementation with conditioned medium prepared from EPO‐3T3‐EGFP cells, the survival rate of PC12‐INT‐EGFP cells was significantly enhanced. Surprisingly, a fraction of aggregated cytoskeletal EGFP‐tagged α‐internexin in PC12‐INT‐EGFP cells was disaggregated and transported into neurites dynamically. The immunocytochemical distribution of IF proteins, including NF‐M, phosphorylated‐NF‐M, and the α‐INT‐EGFP fusion protein, were less aggregated in the perikaryal region and transported into neurites after the EPO treatment.

Conclusion

The established EPO‐overexpressing NIH/3T3 cell line, EPO‐3T3‐EGFP, may provide a material for future studies of cell‐based therapies for neurodegenerative diseases via the secretion of EPO on a short‐term, high‐dose, regional basis.
Application of finite element method for electro‐thermal modeling of metal oxide surge arrester
Authors: Seyyedbarzegar Seyyed Meysam , Mirzaie Mohammad
Published: June 2015

Analysis of electro‐thermal behavior in various operating condition based on finite element method was proposed in this article. Power frequency and impulse stresses vary the operating region and temperature of surge arresters. Therefore, adaptive power loss was considered as a source in the modeling of surge arrester based on finite element method. Adaptive network based fuzzy inference system and frequency dependent model were used to model power loss in low and high current regions, respectively. To obtain accurate power loss, which is very important factor in electro‐thermal analysis, applied voltage and temperature were considered as inputs in adaptive network based fuzzy inference system model. The experimental setup including impulse generator, power frequency high voltage generator and also an oven was arranged to achieve real data. Finally, the results of simulation based on proposed adaptive method were compared with the thermal infrared camera results. This study shows that the electro‐thermal behavior of surge arrester is predictable with a good accuracy by using artificial model. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:910–920, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21663
Expanding the Imine Reductase Toolbox by Exploring the Bacterial Protein‐Sequence Space
Authors: Wetzl Dennis , Berrera Marco , Sandon Nicolas , Fishlock Dan , Ebeling Martin , Müller Michael , Hanlon Steven , Wirz Beat , Iding Hans
Published: June 2015

Recent investigations on imine reductases (IREDs) have enriched the toolbox of potential catalysts for accessing chiral amines, which are important building blocks for the pharmaceutical industry. Herein, we describe the characterization of 20 new IREDs. A C‐terminal domain clustering of the bacterial protein‐sequence space was performed to identify the novel IRED candidates. Each of the identified enzymes was characterized against a set of nine cyclic imine model substrates. A refined clustering towards putative active‐site residues was performed and was consistent both with our screening and previously reported results. Finally, preparative scale experiments on a 100 mg scale with two purified IREDs, IR_20 from Streptomyces tsukubaensis and IR_23 from Streptomyces vidiochromogenes, were carried out to provide (R)‐2‐methylpiperidine in 98 % ee (71 % yield) and (R)‐1‐methyl‐1,2,3,4‐tetrahydroisoquinoline in >98 % ee (82 % yield).
Synthesis of a Cytotoxic Amanitin for Biorthogonal Conjugation
Authors: Zhao Liang , May Jonathan P. , Blanc Antoine , Dietrich David J. , Loonchanta Anastak , Matinkhoo Kaveh , Pryyma Alla , Perrin David M.
Published: June 2015

Alpha‐amanitin is an exceedingly toxic, naturally occurring, bicyclic octapeptide that inhibits RNA polymerase and results in cellular and organismal death. Here we report the straightforward synthesis of an amanitin analogue that exhibited near‐native toxicity. A pendant alkyne was readily installed to enable copper‐catalyzed alkyne–azide cycloaddition (CuAAC) to azido‐rhodamine and two azide‐bearing versions of the RGD peptide. The fluorescent toxin analogue entered cells and provoked morphological changes consistent with cell death. The latter two conjugates are as toxic as the parent alkyne precursor, which demonstrates that conjugation does not diminish toxicity. In addition, we showed that toxicity depends on a single diastereomer of the unnatural amino acid, dihydroxyisoleucine (DHIle), at position 3. The convenient synthesis of a heptapeptide precursor now provides access to bioactive amanitin analogues that may be readily conjugated to biomolecules of interest.
The mammalian target of rapamycin signaling pathway regulates myocyte enhancer factor‐2C phosphorylation levels through integrin‐linked kinase in goat skeletal muscle satellite cells
Authors: Wu Haiqing , Ren Yu , Pan Wei , Dong Zhenguo , Cang Ming , Liu Dongjun
Published: June 2015

Mammalian target of rapamycin (mTOR) signaling pathway plays a key role in muscle development and is involved in multiple intracellular signaling pathways. Myocyte enhancer factor‐2 (MEF2) regulates muscle cell proliferation and differentiation. However, how the mTOR signaling pathway regulates MEF2 activity remains unclear. We isolated goat skeletal muscle satellite cells (gSSCs) as model cells to explore mTOR signaling pathway regulation of MEF2C. We inhibited mTOR activity in gSSCs with PP242 and found that MEF2C phosphorylation was decreased and that muscle creatine kinase (MCK) expression was suppressed. Subsequently, we detected integrin‐linked kinase (ILK) using MEF2C coimmunoprecipitation; ILK and MEF2C were colocalized in the gSSCs. We found that inhibiting mTOR activity increased ILK phosphorylation levels and that inhibiting ILK activity with Cpd 22 and knocking down ILK with small interfering RNA increased MEF2C phosphorylation and MCK expression. In the presence of Cpd 22, mTOR activity inhibition did not affect MEF2C phosphorylation. Moreover, ILK dephosphorylated MEF2C in vitro. These results suggest that the mTOR signaling pathway regulates MEF2C positively and regulates ILK negatively and that ILK regulates MEF2C negatively. It appears that the mTOR signaling pathway regulates MEF2C through ILK, further regulating the expression of muscle‐related genes in gSSCs.
Two‐Step One‐Pot Synthesis of Pinoresinol from Eugenol in an Enzymatic Cascade
Authors: Ricklefs Esther , Girhard Marco , Koschorreck Katja , Smit Martha S. , Urlacher Vlada B.
Published: June 2015

The phytoestrogen pinoresinol is a high‐value compound that has a protective effect against diverse health disorders, and thus is of interest for the pharmaceutical industry. Isolation of pinoresinol from plants suffers from low yields, and its chemical synthesis involves several work‐up steps. In this study we devised a novel two‐step one‐pot enzymatic cascade combining a vanillyl‐alcohol oxidase and a laccase for the production of pinoresinol from eugenol via the intermediate coniferyl alcohol. Along with the well‐characterized vanillyl‐alcohol oxidase from Penicillium simplicissimum used to catalyze the oxidation of eugenol, enzyme screening revealed three bacterial laccases that were appropriate for the synthesis of pinoresinol from coniferyl alcohol. The cascade was optimized regarding enzyme ratios, pH value, and the presence of organic solvents. Under optimized conditions, pinoresinol concentration achieved 4.4 mM (1.6 g l−1), and this compound was isolated and analyzed.
Insights into the Oxidation State and Location of Rhenium in Re‐Pd/TiO2 Catalysts for Aqueous‐Phase Selective Hydrogenation of Succinic Acid to 1,4‐Butanediol as a Function of Palladium and Rhenium Deposition Methods
Authors: Ly Bao Khanh , Tapin Benoît , Aouine Mimoun , Delichere Pierre , Epron Florence , Pinel Catherine , Especel Catherine , Besson Michèle
Published: June 2015

ReOx‐Pd/TiO2 catalysts prepared from different 2 wt %Pd/TiO2 catalysts using two protocols for the deposition of the Re promoter (successive impregnation and catalytic reduction) were characterized by different techniques to better understand the nature of the active and selective sites implied in the aqueous‐phase hydrogenation of succinic acid to 1,4‐butanediol. Regardless of the support and Re introduction method, it was established that varying amounts of Pd and Re were in very close proximity without electronic interaction in the reduced catalysts. A high fraction of Re always remained partially oxidized to generate a bimetallic catalyst that can provide the necessary bifunctional sites to enable the selective hydrogenolysis of the intermediate γ‐butyrolactone to 1,4‐butanediol. Depending on the method of promotion, the ReOx species that interact with Pd were deposited as clusters with different spatial Re–Re interactions.
4‐CH3CONH–TEMPO/Peracetic Acid System for a Shortened Electron‐Transfer‐Cycle‐Controlled Oxidation of Secondary Alcohols
Authors: Zhang Shufang , Miao Chengxia , Xia Chungu , Sun Wei
Published: June 2015

We have developed a 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) derivative catalyzed oxidation of secondary alcohols with peracetic acid as the oxidant, which was generated from H2O2 and acetic acid catalyzed by strongly acidic resins. The oxidation of alcohols proceeded well through a shortened electron‐transfer cycle under metal‐free conditions, avoiding the use of any other electron‐transfer mediators such as halides. In addition, we demonstrated that the present system exhibited excellent efficiency under mild conditions for the oxidation of aromatic, aliphatic, and allylic secondary alcohols.
Mapping the Interactions of I2, I., I−, and I+ with Alkynes and Their Roles in Iodocyclizations
Authors: Volpe Rohan , Aurelio Luigi , Gillin Murray G. , Krenske Elizabeth H. , Flynn Bernard L.
Published: June 2015

A combination of experiment and theory has been used to explore the mechanisms by which molecular iodine (I2) and iodonium ions (I+) activate alkynes towards iodocyclization. Also included in the analysis are the roles of atomic iodine (I.) and iodide ion (I−) in mediating the competing addition of I2 to the alkyne. These studies show that I2 forms a bridged I2–alkyne complex, in which both alkyne carbons are activated towards nucleophilic attack, even for quite polarized alkynes. By contrast, I+ gives unsymmetrical, open iodovinyl cations, in which only one carbon is activated toward nucleophilic attack, especially for polarized alkynes. Addition of I2 to alkynes competes with iodocyclization, but is reversible. This fact, together with the capacity of I2 to activate both alkyne carbons towards nucleophilic attack, makes I2 the reagent of choice (superior to iodonium reagents) for iodocyclizations of resistant substrates. The differences in the nature of the activated intermediate formed with I2 versus I+ can also be exploited to accomplish reagent‐controlled 5‐exo/6‐endo‐divergent iodocyclizations.
Lewis Acid Catalyzed Condensation–Cyclization Cascade: Direct Synthesis of Di/Trifluoromethyl‐1,2,3,4‐tetrahydroquinazolines
Authors: Prakash G. K. Surya , Papp Attila , Munoz Socrates B. , May Nathan , Jones John‐Paul , Haiges Ralf , Esteves Pierre Mothé , Mathew Thomas
Published: June 2015

Condensed heterocycles such as quinazolines constitute the framework of many promising drugs. The great impact of the dramatic fluorine effect in pharmaceuticals prompted a great surge in the quest for fluorinated drug design resulting in over 20 % fluorine‐containing drugs in the market today. Therefore, finding an efficient and cost‐effective method for the direct synthesis of fluorine‐tagged quinazoline systems is of great significance in the pharmaceutical arena. For the first time, a one‐pot sequential condensation–cyclization reaction to form selectively the difluoro/trifluoromethylated tetrahydroquinazolines from simple components difluoro/trifluoroacetaldehyde hemiacetal and aromatic amines is reported. Our recent studies using difluoro/trifluoroacetaldehyde hemiacetal as simple and elegant difluoro/trifluoromethyl synthons and metal triflates such as gallium triflate as safe and stable Lewis acid catalysts led us to this direct synthesis protocol for the expedient and convenient synthesis of fluorinated quinazolines. DFT calculations at PCM/B3LYP/6‐31++G** were carried out for evaluating a possible reaction mechanism for this cyclization. According to the DFT calculations, product stereochemistry is thermodynamically driven, favoring the cis isomer as the major product, which is also confirmed experimentally.
Direct Synthesis of Chiral 3‐Arylsuccinimides by Rhodium‐Catalyzed Enantioselective Conjugate Addition of Arylboronic Acids to Maleimides
Authors: Gopula Balraj , Yang Shu‐Han , Kuo Ting‐Shen , Hsieh Jen‐Chieh , Wu Ping‐Yu , Henschke Julian P. , Wu Hsyueh‐Liang
Published: June 2015

Chiral rhodium catalysts comprising 2,5‐diaryl‐ substituted bicyclo[2.2.1]diene ligands L1–L10 were utilized in the enantioselective 1,4‐addition reaction of arylboronic acids to N‐substituted maleimides. In the presence of 2.5 mol % of RhI/L2, enantioenriched conjugate addition adducts were isolated in 72–99 % yields with 86–98 % ee. This protocol offers a convenient method to access a variety of 3‐arylsuccinimides in a highly enantioselective manner. Maleimides with readily cleavable N‐protecting groups were tolerated enabling the synthesis of useful synthetic intermediates. Pyrrolidine 4, a biologically active compound, and pyrrolidine 5, an ent‐precursor to an HSD‐1 inhibitor, were synthesized to demonstrate the utility of this method.
A Series of Lanthanide Metal–Organic Frameworks with Interesting Adjustable Photoluminescence Constructed by Helical Chains
Authors: Liu Ying , Zhang Yu , Hu Gong Hao , Zhou Shuai , Fan Ruiqing , Yang Yulin , Xu Yan
Published: June 2015

Based on the isonicotinic acid (HIN=pyridine‐4‐carboxylic acid), seven lanthanide metal–organic frameworks (MOFs) with the formula [Ln(IN)2L] (Ln=Eu (1), Tb (2), Er (3), Dy (4), Ho (5), Gd (6), La (7), L=OCH2CH2OH) have been synthesized by mixing Ln2O3 with HIN under solvothermal conditions, and characterized by single‐crystal X‐ray diffraction, powder X‐ray diffraction, infrared spectroscopy, and fluorescence spectroscopy. Crystal structural analysis shows that compounds 1–6 are isostructural, crystallize in a chiral space group P212121, whereas compound 7 crystallizes in space group C2/c. Nevertheless, they all consist of new intertwined chains. Simultaneously, on the basis of the above‐mentioned compounds, we have realized a rational design strategy to form the doped Ln MOFs [(EuxTb1−x)(IN)2L] (x=0.35 (8), x=0.19 (9), x=0.06 (10)) by utilizing TbIII as the second “rare‐earth metal”. Interestingly, the photoluminescence of [(EuxTb1−x)(IN)2L] are not only adjustable by the ratios of Eu/Tb, but also temperature or excitation wavelength.
The Effects of Stagnant Slabs on the Topography of 410 km Discontinuity Beneath the Pamir‐Hindu Kush Region
Authors: Yi SUI , Yuan‐Ze ZHOU , Xiao‐Ran WANG
Published: June 2015

The effects of stagnant slabs on the topography of the 410 km discontinuity is helpful in determining the composition of the Earth's interior and understanding the relevant geodynamical processes. The Pamir‐Hindu Kush region is a rare subduction area subject to intermediate and deep earthquakes whose waveforms can be used to map the topography of the 410 km discontinuity. Broadband/short period waveform data from six earthquakes in the subducted slabs beneath the Pamir‐Hindu Kush region recorded by the Hi‐net seismic network, Japan and one recorded by the TA seismic array, USA, were processed using the 4‐th root slant stack method. The focal depths of the earthquakes were between 154.0 and 220.9 km, and their body wave magnitudes were between Mb 5.6 and 6.4. The conversion SdP phases at the velocity interfaces were found from 36 vespegrams, and the conversion depths near the 410 km discontinuity were determined based on the IASP91 model. The 410 km discontinuity is uplifted to depths between 372 and 398 km. Compared with slabs in western Pacific subducting regions, the stagnant subducted slab causes a smaller impact on the topography of the 410 km discontinuity.
A Statistical Analysis of Solar Wind Parameters and Geomagnetic Indices during the Solar Cycle 23
Authors: Xiao‐Fei SHEN , Bin‐Bin NI , Xu‐Dong GU , Chen ZHOU , Yong LIU , Zheng XIANG , Zheng‐Yu ZHAO
Published: June 2015

Interplanetary Coronal mass ejections (CMEs) and corotating interaction regions (CIRs) are two types of most geoeffective solar wind transients and also the main drivers of geomagnetic storms. In this study, by using a superposed epoch analysis, we have compared the statistical features of solar wind parameters for the two types of solar disturbances during the 23rd solar cycle and the resulting changes of geomagnetic indices (Dst, AE, and Kp). Meanwhile, the statistics of solar wind parameters and geomagnetic indices corresponding to magnetic storms with different intensities are also investigated. In general, it is found that the slopes of linearly fitted Nsw/Pdyn curves (where Nsw is the solar wind proton density and Pdyn is the solar wind dynamic pressure) with respect to epoch time remains positive for CME events but negative for CIR events, which can act as a feasible means to distinguish CME and CIR events. On average, compared to CIR events, CME events have larger magnitudes of southward IMF Bz, solar wind dynamic pressure, AE and Kp indices but smaller Dstmin. In principle, CMEs bear higher possibility to drive extremely intense (i.e., super) geomagnetic storms. The overall variations of Dst tend to be similar to some extent for different levels of geomagnetic storms, however, Dst decreases faster for stronger storms.
A spectral framework forNMRsignal with restricted diffusion
Authors: Bar Leah , Sochen Nir
Published: June 2015

By the multiple correlation function (MCF) formalism, the nuclear magnetic resonance magnetization of diffusing spins can be represented for simple pore geometries. It may be used to infer geometric structure at the scale of microns. This is to be compared to the diffusion tensor imaging, which provides geometric information at the scale of millimeters. The MCF formulation was derived to special cases in which the gradients of the magnetic field are oriented in specific directions. A generalized approach allowing an arbitrary magnetic field direction was introduced by Özarslan. In this article, we present a complete account of the generalized MCF mathematical derivation starting from Bloch–Torrey equations. It is aimed to the experts and novices alike. We present two approaches—the indirect derivation is based on Özarslan's work, where the standard MCF equations are adopted to arbitrary gradient directions. Our alternative approach is based on direct calculations of the MCF matrices for specified gradient directions. We prove that the two approaches lead to the same equations. Finally, we revise Mitra's microscopic approach and show the relation to the macroscopic MCF approach. We prove that in some limit conditions the two signal equations coincide © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part A 43A: 16–53, 2015.
What is the optimal management of early‐stage low‐grade follicular lymphoma in the modern era?
Authors: Vargo John A. , Gill Beant S. , Balasubramani Goundappa K. , Beriwal Sushil
Published: June 2015

BACKGROUND

Despite international practice guidelines endorsing radiotherapy (RT) as the preferred initial therapy, treatment approaches vary for patients with early‐stage follicular lymphoma. The authors engaged the National Cancer Data Base to analyze patterns of care and survival outcomes for patients with early‐stage follicular lymphoma in the era of modern therapy.

METHODS

A National Cancer Data Base retrospective cohort study was conducted of 35,961 patients with lymph node and extranodal, American Joint Committee on Cancer stage I to II, WHO grade 1 to 2 follicular lymphoma who were diagnosed between 1998 and 2012. Univariate and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics that were predictive of overall survival (OS) and treatment use. Propensity score‐adjusted Cox proportional hazards ratios for survival in patients treated for follicular lymphoma were used.

RESULTS

Of the 35,961 patients with follicular lymphoma included in the current study, 63% had stage I disease, 79% were without extranodal disease, and 61% were aged >60 years. RT use decreased from 37% in 1999 to 24% in 2012 (P<.0001), with corresponding significant increases in observation and single‐agent chemotherapy. Patients who received RT had 5‐year and 10‐year OS rates of 86% and 68%, respectively, compared with 74% and 54%, respectively, for those who did not receive RT (P<.0001). On multivariable survival analysis, including a propensity score to account for potential uncaptured confounding variables due to a lack of randomization, upfront RT remained independently associated with improved OS (hazard ratio of death, 0.54; 95% confidence interval, 0.47‐0.63 [P<.0001]).

CONCLUSIONS

RT is an increasingly underused treatment approach in the era of modern therapy for patients with early‐stage follicular lymphoma. The use of RT appears to improve OS and should remain standard practice as encouraged by clinical practice guidelines. Cancer 2015;121:3325–3334. © 2015 American Cancer Society.
Graphitic Carbon Nitride/Graphene Hybrids as New Active Materials for Energy Conversion and Storage
Authors: Zhao Yang , Zhang Jing , Qu Liangti
Published: June 2015

Energy conversion and storage devices play an important role in industry and society with the rapid growth of energy consumption. Developing a highly efficient, environmentally friendly device mainly depends on improvements in high‐performance electrode materials or catalysts. Recently, graphitic carbon nitride/graphene (g‐C3N4/graphene) hybrids have drawn considerable attention and shown great potential as active materials in the field of energy conversion and storage due to their unique and tunable nanostructure, high nitrogen content, and conductivity. This review focuses on the recent significant advances in the fabrication and application of g‐C3N4/graphene hybrids as electro‐ or photocatalysts and electrode materials. Synthetic strategies and applications for photo‐ or electro‐related devices are presented, accompanied with a discussion of the challenges and research directions for the future development of g‐C3N4/graphene hybrids.
Template‐Guided Ionic Self‐Assembled Molecular Materials and Thin Films with Nanoscopic Order
Authors: Santella Marco , Amini Fatima , Andreasen Kristian B. , Aswad Dunya S. , Ausar Helene , Austin Lillian Marie , Bora Ilkay , Boye Ida M. I. , Brinkenfeldt Nikolaj K. , Bøe Magnus F. , Cakmak Emine , Catovic Alen , Christensen Jonas M. , Dalgaard Jonas H. , Danielsen Helena Maria D. , Bouyahyaoui Abdel H. El , Dib Sarah E. H. El , Khaiyat Btihal El , Farooq Iqra , Fjellerup Freja K. , Frederiksen Gregers W. , Frederiksen Henriette R. S. , Gleerup David , Gold Mikkel , Gruber Morten F. , Gylling Mie , Heidari Vita , Herzberg Mikkel , Holgaard U. Laurens D. , Hundahl Adam C. , Hviid Rune , Høhling Julian S. , Abd Issa Fatima Z. , Jakobsen Nicklas R. , Jakobsen Rasmus K. , Jensen Benjamin L. , Jensen Phillip W. K. , Juelsholt Mikkel , Liao Zhiyu , Le Chung L. , Mayanja Ivan F. , Moustafa Hadeel , Møller Charlie B. B. , Nielsen Cecilie L. , Nielsen Marius R. J. E. H. , Nielsen Søren S.‐R. , Olsen Markus J. , Paludan Bandula D. , Prestholm Idunn , Qoqaj Iliriana , Riel Christina B. , Rostgaard Tobias V. , Saleh Nora , Schultz Hannibal M. , Standland Mark , Svenningsen Jens S. , Sørensen Rasmus Truels , Visby Jesper , Wolff‐Sneedorff Emilie L. , Zachariassen Malte Hee , Ziari Edmond A. , Sørensen Henning O. , Sørensen Thomas Just
Published: June 2015

Ionic self‐assembly (ISA) is a proven method that exploits non‐covalent interactions to generate supramolecular materials. Here, we have expanded the scope of this approach fabricating thin films with nanoscopic order maintained over centimeters. Cationic layers of benzalkonium surfactants form a lamellar template. The template is able to host layers of negatively charged polyaromatic functional units, here demonstrated with β‐naphthol‐derived azo‐dyes. We show that a variety of these functional building blocks can be incorporated in the lamellar template through ISA. Sixteen different materials were produced, characterized, and processed into thin films, with lamellar order perpendicular to the substrate. Thus, a design concept is demonstrated in which diverse functional motifs can be isolated and ordered in a 2D lattice between layers of alkyl chains in bulk and in thin films, in which the molecular order is maintained and aligned to the substrate.
Local Control Theory in Trajectory Surface Hopping Dynamics Applied to the Excited‐State Proton Transfer of 4‐Hydroxyacridine
Authors: Curchod Basile F. E. , Penfold Thomas J. , Rothlisberger Ursula , Tavernelli Ivano
Published: June 2015

The application of local control theory combined with nonadiabatic ab initio molecular dynamics to study the photoinduced intramolecular proton transfer reaction in 4‐hydroxyacridine was investigated. All calculations were performed within the framework of linear‐response time‐dependent density functional theory. The computed pulses revealed important information about the underlying excited‐state nuclear dynamics highlighting the involvement of collective vibrational modes that would normally be neglected in a study performed on model systems constrained to a subset of the full configuration space. This study emphasizes the strengths of local control theory for the design of pulses that can trigger chemical reactions associated with the population of a given molecular excited state. In addition, analysis of the generated pulses can help to shed new light on the photophysics and photochemistry of complex molecular systems.