bluuebunny/crossref_metadata_2025_split huggingface dataset:
SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria
Authors: Chino Yukihiro , Samukawa Yoshishige , Sakai Soichi , Nakai Yasuhiro , Yamaguchi Jun‐ichi , Nakanishi Takeo , Tamai Ikumi 
Published: July 2014

ABSTRACTSodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d‐glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d‐glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans‐stimulated by 10 mm d‐glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis‐inhibited by 100 mm d‐glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin‐induced glycosuria, with alterations of UA transport activity because of urinary glucose. © 2014 The Authors. Biopharmaceutics & Drug Disposition. Published by John Wiley & Sons Ltd.
Luminescence properties of red‐emission Mg4Nb2O9:Eu3+ phosphor
Authors: Cao Renping , Cao Chunyan , Yu Xiaoguang , Qiu Jianrong 
Published: July 2014

ABSTRACTRed‐emitting Mg4Nb2O9:Eu3+ phosphor is synthesized via a solid‐state reaction method in air, and its crystal structure and luminescence are investigated. The phosphor can be excited efficiently by ~ 395 nm light, coupled well with a ~ 395 nm near‐ultraviolet chip and emits red light at ~ 613 nm with sharp spectra due to 5D0 → 7 F2 transition of the Eu3+ ion. Mg4Nb2O9:Eu3+ phosphor sintered at 1350 ºC shows Commission international de I'Eclairage (CIE) chromaticity coordinates of x = 0.6354, y = 0.3592, and is a potential red‐emitting phosphor candidate for white light‐emitting diodes (W‐LEDs) under ~ 395 nm near‐ultraviolet LED chip excitation. Copyright © 2014 John Wiley & Sons, Ltd.
Removal of cleavage slow points from affinity tags used in the IMAC purification of recombinant proteins
Authors: Mooney Jane T. , Fredericks Dale , Christensen Thorkild , Hearn Milton T. W. 
Published: July 2014

AbstractThe complete enzymatic removal of affinity tags from tagged recombinant proteins is often required but can be challenging when slow points for cleavage exist. This study documents a general approach to remove N‐terminal tags from recombinant proteins specifically designed to be efficiently captured by IMAC resins. In particular, site‐directed mutagenesis procedures have been used to modify the amino acid sequence of metal binding tags useful in IMAC purifications of recombinant proteins with the objective to increase cleavage efficiency with the exopeptidase, dipeptidyl aminopeptidase 1. These tags were specifically developed for application with borderline metal ions, such as Ni2+ or Cu2+ ions, chelated to the immobilized ligands, 1,4,7‐triazacyclononane (tacn) and its analogs. Due to the ability to control cleavage site structure and accessibility via site directed mutagenesis methods, these procedures offer considerable scope to obtain recombinant proteins with authentic native N‐termini, thus avoiding any impact on structural stability, humoral and cellular immune responses, or other biological functions. Collectively, these IMAC‐based methods provide a practical alternative to other procedures for the purification of recombinant proteins with tag removal. Overall, this approach is essentially operating as an integrated down‐stream purification capability.
Humanized antibody neutralizing 2009 pandemic H1N1 virus
Authors: Shembekar Nachiket , Mallajosyula Vamsee V Aditya , Chaudhary Piyush , Upadhyay Vaibhav , Varadarajan Raghavan , Gupta Satish Kumar 
Published: July 2014

AbstractThe 2009 pandemic H1N1 S‐OIV (swine origin influenza A virus) caused noticeable morbidity and mortality worldwide. In addition to vaccine and antiviral drug therapy, the use of influenza virus neutralizing monoclonal antibodies (MAbs) for treatment purposes is a viable alternative. We previously reported the isolation of a high affinity, potently neutralizing murine MAb MA2077 against 2009 pandemic H1N1 virus. We describe here the humanization of MA2077 and its expression in a mammalian cell line. Six complementarity‐determining regions (CDRs) of MA2077 were grafted onto the human germline variable regions; along with six and eight back mutations in the framework of heavy and light chains, respectively, pertaining to the vernier zone and interchain packing residues to promote favorable CDR conformation and facilitate antigen binding. The full length humanized antibody, 2077Hu2, expressed in CHO‐K1 cells, showed high affinity to hemagglutinin protein (KD = 0.75 ± 0.32 nM) and potent neutralization of pandemic H1N1 virus (IC50 = 0.17 μg/mL), with marginally higher IC50 as compared to MA2077 (0.08 μg/mL). In addition, 2077Hu2 also retained the epitope specificity for the “Sa” antigenic site on pandemic HA. To the best of our knowledge, this is the first report of a humanized neutralizing antibody against pandemic H1N1 virus.
The Importance of the Diverse Drivers and Types of Environmental Innovation for Firm Performance
Authors: Doran Justin , Ryan Geraldine 
Published: July 2014

AbstractToday, firms are faced with a number of environmental challenges, such as global warming, pollution control and declining natural resources. While there is increasing pressure to deliver environmentally friendly products and services, little is known about what drives the many different types of environmental innovation, or how such pursuits' impact firm performance. Using a sample of 2181 firms, this paper examines the factors that drive nine different types of eco‐innovation in Ireland, and assesses how such innovations impact firm performance. We find that, while demand‐side, supply‐side and regulatory drivers impact on the likelihood of a firm engaging in eco‐innovation, the relative magnitudes of these impacts vary across the types of eco‐innovation considered. Moreover, we find that only two of the nine types of eco‐innovation positively impact firm performance. The results point to regulation and customer pressure as viable mechanisms through which firms can be encouraged to eco‐innovate. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Bcl‐2 down‐regulation by small interfering RNA induces Beclin1‐dependent autophagy in human SGC‐7901 cells
Authors: Du Yun , Ji Xiaokun 
Published: July 2014

AbstractWhile Bcl‐2 protein is involved in the regulation of apoptosis, recent research showed that Beclin1, described as the essential autophagy effector and haploinsufficient tumor suppressor, was originally isolated as a Bcl‐2 interacting protein. Beclin1 interacts with Bcl‐2 through a BH3 domain; nevertheless, the function of the anti‐apoptotic gene, Bcl‐2, in autophagy is not well understood. We explored the role of Bcl‐2 in autophagy in human SGC‐7901 cells in which Bcl‐2 is overexpressed. Knockdown of Bcl‐2 by small interfering RNA in human SGC‐7901 cells downregulated Bcl‐2 protein levels ∼82% and induced autophagy. Beclin1 protein, the first identified autophagy gene product, was induced by as much as 58%. Transmission electron microscopy and DNA fragmentation assay showed that autophagy was enhanced, but not apoptosis, in Bcl‐2 siRNA treated cells. The results provide evidence that knockout the anti‐apoptotic gene Bcl‐2 induces autophagy in SGC‐7901 cells and Bcl‐2 specific siRNA may be used as a potential therapeutic strategy in gastric cancer cells that overexpress Bcl‐2.
Role of p53 in preadipocyte differentiation
Authors: Huang Qiong , Liu Menglan , Du Xinli , Zhang Rihua , Xue Yi , Zhang Yuanyuan , Zhu Weidong , Li Dong , Zhao Allan , Liu Yun 
Published: July 2014

AbstractInsulin resistance, diabetes and many kinds of cancers are common in overweight and obese individuals. The tumor suppressor p53 is important in securing genetic stability, but its role in the regulation of metabolic processes and cell differentiation remains unclear. We have investigated the role of p53 in adipocyte differentiation. Using 3T3‐L1 cells, a mouse embryonic fibroblast preadipocyte model and DIO rat model, p53 expression and function during adipocyte differentiation were investigated. p53 expression increased on the second and fourth day of adipocyte differentiation and decreased thereafter. Its overexpression in 3T3‐L1 preadipocytes markedly reduced adipogenesis and marker gene expression. p53 activity was weakened in DIO rat abdominal adipose tissue because of an decreased expression of its activated phosphorylated form. In contrast, p53 knockout enhanced adipogenesis and the expression of marker genes, but significantly reduced insulin‐stimulated Akt phosphorylation. These results indicate that p53 partly suppresses preadipocyte differentiation and adipogenesis by regulating adipocyte gene expression and Akt signaling.
Isobutane Dehydrogenation over Metal (Fe, Co, and Ni) Oxide and Sulfide Catalysts: Reactivity and Reaction Mechanism
Authors: Wang Guowei , Gao Chuancheng , Zhu Xiaolin , Sun Yanan , Li Chunyi , Shan Honghong 
Published: July 2014

AbstractSilica‐supported metal oxide and sulfide catalysts of Fe, Co, and Ni were evaluated comparatively for the catalytic dehydrogenation of isobutane. The results of the activity test and temperature‐programmed reduction of hydrogen characterization indicate that metal oxides, except Fe2O3, are easily reduced to metal ensembles, which are extremely active for alkane hydrogenolysis and lead to the formation of a considerable amount of methane and coke. However, the dehydrogenation performance was significantly improved after sulfidation treatment. The introduction of sulfur affects the catalysts in two ways: one is the geometric effect, which dilutes the aggregated metallic species and reduces hydrogenolysis activity, and the other is the electronic effect, which facilitates the desorption of olefin and increases the product selectivity. Moreover, the reaction mechanism is explored by using the proposed model of the interaction between isobutane and sulfide catalysts. Finally, sulfur loss and partial coke deposition are determined to be the main reasons for catalyst deactivation.
Synthesis and Solution Studies of Silver(I)‐Assembled Porphyrin Coordination Cages
Authors: Durot Stéphanie , Flamigni Lucia , Taesch Julien , Dang Tung T. , Heitz Valérie , Ventura Barbara 
Published: July 2014

AbstractThe synthesis and the characterization of two porphyrin coordination cages are reported. The design of the cage formation is based on the coordination of silver(I) ions to the pyridyl units of 3‐pyridyl appended porphyrins. 1H/109Ag NMR spectroscopy, and diffusion‐ordered spectroscopy (DOSY) experiments demonstrate that both the free base porphyrin 2H‐TPyP and the Zn‐porphyrin Zn‐TPyP form the closed cages, [Ag4(2H‐TPyP)2]4+ and [Ag4(Zn‐TPyP)2]4+, respectively, upon addition of two equivalents of Ag+. The complexation processes are characterized in details by means of absorption and emission spectroscopy in diluted CH2Cl2 solutions. The data are discussed in the frame of the point‐dipole exciton coupling theory; the two porphyrin monomers, in fact, experience a rigid face‐to‐face geometry in the cages and a weak inter‐porphyrin exciton coupling. An intermediate species is observed, for Zn‐TPyP, in a porphyrin/Ag+ stoichiometric ratio of about 1:0.5 and is tentatively ascribed to an oblique open form. The occurrence of a photoinduced electron‐transfer reaction within the cages is excluded on the basis of the experimental outcomes and thermodynamic evaluations. Photophysical experiments evidence different reactivities of singlet and triplet excited states in the assemblies. A lower fluorescence quantum yield and triplet formation is discussed in relation to the constrained geometry of the complexes. Unusually long triplet excited state lifetimes are measured for the assemblies.
Stereoselective Aminoxylation of Biradical Titanium Enolates with TEMPO
Authors: Gómez‐Palomino Alejandro , Pellicena Miquel , Romo Juan Manuel , Solà Ricard , Romea Pedro , Urpí Fèlix , Font‐Bardia Mercè 
Published: July 2014

AbstractA highly efficient and straightforward aminoxylation of titanium(IV) enolates from (S)‐N‐acyl‐4‐benzyl‐5,5‐dimethyl‐1,3‐oxazolidin‐2‐ones with TEMPO has been developed. A wide array of functional groups on the acyl moiety, including alkyl and aryl substituents, olefins, esters, or α‐cyclopropyl, as well as α‐trifluoromethyl groups, are well tolerated. This transformation can therefore produce the α‐aminoxylated adducts in excellent yields with high diastereomeric ratios (d.r.). In turn, parallel additions to the α,β‐unsaturated N‐acyl counterparts give the corresponding γ‐adducts with complete regioselectivity in moderate to good yields. Removal of the piperidinyl moiety or the chiral auxiliary converts the resultant adducts into enantiomerically pure α‐hydroxy carboxyl derivatives, alcohols, or esters in high yields under mild conditions. Finally, a new mechanistic model based on the biradical character of the titanium(IV) enolates has been proposed.
Semiconductor and Metallic Core–Shell Nanostructures: Synthesis and Applications in Solar Cells and Catalysis
Authors: Kim Mee Rahn , Xu Zhenhe , Chen Guozhu , Ma Dongling 
Published: July 2014

AbstractNano‐heterostructures have attracted great attention due to their extraordinary properties beyond those of their single‐component counterparts. This review focuses on a specific type of hybrid structures: core–shell structures. In particular, we present and discuss the recent wet‐chemical synthesis approaches for semiconductor and metallic core–shell nanostructures, and their relevant properties and potential applications in photovoltaics and catalysis, respectively.
Eaton’s Reagent‐Mediated Domino π‐Cationic Arylations of Aromatic Carboxylic Acids to Iasi‐Red Polymethoxylated Polycyclic Aromatic Hydrocarbons: Products with Unprecedented Biological Activities as Tubulin Polymerization Inhibitors
Authors: Ghinet Alina , Gautret Philippe , Hijfte Nathalie Van , Ledé Bertrand , Hénichart Jean‐Pierre , Bîcu Elena , Darbost Ulrich , Rigo Benoît , Daïch Adam 
Published: July 2014

AbstractA rapid domino π‐cationic arylation of aromatic carboxylic acids, mediated by Eaton’s reagent, has been developed for the synthesis of Iasi‐red polymethoxylated polycyclic aromatic hydrocarbons (PAHs). This route is currently the easiest method to obtain such popular PAH compounds, which bear in addition numerous methoxy groups. The domino process was generalized, the structure of the obtained red products and the mechanism of their formations were elucidated, and some of their photophysical properties were determined. Newly synthesized polymethoxylated‐PAHs were tested for their interaction with tubulin polymerization as well as for their cytotoxicity on a panel of NCI‐60 human cancer cell lines. Interestingly, one of these rubicene derivatives exhibited remarkable cytotoxicity in vitro, including inhibition of leukemia, colon, melanoma, CNS, and ovarian cancer cell lines with GI50 values in the low nanomolar range (GI50<10 nM).
Configuration‐ and Conformation‐Dependent Electronic‐Structure Variations in 1,4‐Disubstituted Cyclohexanes Enabled by a Carbon‐to‐Silicon Exchange
Authors: Emanuelsson Rikard , Löfås Henrik , Wallner Andreas , Nauroozi Djawed , Baumgartner Judith , Marschner Christoph , Ahuja Rajeev , Ott Sascha , Grigoriev Anton , Ottosson Henrik 
Published: July 2014

AbstractCyclohexane, with its well‐defined conformers, could be an ideal force‐controlled molecular switch if it were to display substantial differences in electronic and optical properties between its conformers. We utilize σ conjugation in heavier analogues of cyclohexanes (i.e. cyclohexasilanes) and show that 1,4‐disubstituted cyclohexasilanes display configuration‐ and conformation‐dependent variations in these properties. Cis‐ and trans‐1,4‐bis(trimethylsilylethynyl)cyclohexasilanes display a 0.11 V difference in their oxidation potentials (computed 0.11 V) and a 0.34 eV difference in their lowest UV absorption (computed difference between first excitations 0.07 eV). This is in stark contrast to differences in the corresponding properties of analogous all‐carbon cyclohexanes (computed 0.02 V and 0.03 eV, respectively). Moreover, the two chair conformers of the cyclohexasilane trans isomer display large differences in electronic‐structure‐related properties. This enables computational design of a mechanically force‐controlled conductance switch with a calculated single‐molecule ON/OFF ratio of 213 at zero‐bias voltage.
Switching of Single‐Molecule Magnetic Properties of TbIII–Porphyrin Double‐Decker Complexes and Observation of Their Supramolecular Structures on a Carbon Surface
Authors: Inose Tomoko , Tanaka Daisuke , Tanaka Hirofumi , Ivasenko Oleksandr , Nagata Toshi , Ohta Yusuke , De Feyter Steven , Ishikawa Naoto , Ogawa Takuji 
Published: July 2014

AbstractDouble‐decker complexes based on single‐molecule magnets (SMMs) are a class of highly promising molecules for applications in molecular spintronics, wherein control of both the ligand oxidative states and the 2D supramolecular structure on carbon materials is of great importance. This study focuses on the synthesis and study of 2,3,7,8,12,13,17,18‐octaethylporphyrin (OEP)–TbIII double‐decker complexes with different electronic structures comprising protonated, anionic, and radical forms. Magnetic susceptibility measurements revealed that only the anionic and radical forms of the OEP–TbIII double‐decker complexes exhibited SMM properties. The barrier heights for magnetic moment reversal were estimated to be 207 and 215 cm−1 for the anionic and radical forms, respectively. Scanning tunneling microscopy (STM) investigations revealed that these OEP–TbIII complexes form well‐ordered monolayers upon simple dropcasting from dilute dichloromethane solutions. All three complexes form an isomorphic pseudo‐hexagonal 2D pattern, regardless of the differences in the electronic structures of their porphyrin–Tb cores. This finding is of interest for SMM technology as ultrathin films of these materials undergoing chemical transformations will not require any detrimental reorganization. Finally, we demonstrate self‐assembly of the protonated 5,15‐bisdodecylporphyrin (BDP)–TbIII double‐decker complex as an example of successful supramolecular design to achieve controlled alignment of SMM‐active sites.
Outstanding Chiroptical Properties: A Signature of Enantiomerically Pure Alleno–Acetylenic Macrocycles and Monodisperse Acyclic Oligomers
Authors: Donckele Etienne J. , Gidron Ori , Trapp Nils , Diederich Francois 
Published: July 2014

AbstractA second series of shape‐persistent alleno–acetylenic macrocycles and monodisperse acyclic oligomers with conformationally less flexible backbones were synthesized in enantiomerically pure form by short, high‐yielding routes starting from optically active 1,3‐diethynylallenes. All seven stereoisomers—two pairs of enantiomers and three achiral stereoisomers—in the macrocyclic series were separated and configurationally assigned. The electronic circular dichroism (ECD) spectra of the D2‐symmetric, (P,P,P,P)‐ and (M,M,M,M)‐configured macrocycles display remarkably intense chiroptical responses. A strong amplification of chirality is observed in the acyclic oligomeric series. Their preference for helical secondary structures of one handedness was supported by X‐ray analysis and computational studies. This new set of data provides proof that outstanding ECD responses are a hallmark of alleno–acetylenic macrocyclic and acyclic oligomeric chromophores.
[(p‐Cymene)RuCl2]2: An Efficient Catalyst for Highly Regioselective Allylic Alkylations of Chelated Amino Acid Ester Enolates
Authors: Bayer Anton , Kazmaier Uli 
Published: July 2014

AbstractChelated amino acid ester enolates are excellent nucleophiles for ruthenium‐catalyzed allylic alkylations. Although [Cp*Ru(MeCN)3]PF6 was found to be the most reactive catalyst investigated, with the resulting allyl complexes reacting at temperatures as low as −78 °C, unfortunately the process took place with only moderate regio‐ and diastereoselectivity. In contrast, [(p‐cymene)RuCl2]2 allowed allylations to be performed with a high degree of regioretention. Secondary allyl carboxylates with a terminal double bond were found to be the most reactive substrates, giving rise to the branched amino acids with perfect regioretention and chirality transfer. In this case, no isomerization of the Ru–allyl complex formed in situ was observed, in contrast to the analogues palladium complexes. This isomerization‐free protocol can also be used for the synthesis of (Z)‐configured γ,δ‐unsaturated amino acid derivatives, starting from (Z)‐allylic substrates. Here, the more reactive phosphates were found to be superior to the carboxylates, providing the required amino acids in almost quantitative yield with perfect regio‐ and stereoretention. Therefore, the Ru‐catalyzed allylation reactions are well positioned to overcome the drawbacks of Pd‐catalyzed processes.
UV‐Cured, Platinum‐Free, Soft Poly(dimethylsiloxane) Networks
Authors: Goswami K. , Skov A. L , Daugaard A. E. 
Published: July 2014

AbstractTo overcome the drawbacks exhibited by platinum‐catalyzed curing of silicones, photoinitiated thiol–ene cross‐linking of high‐molecular‐weight poly(dimethylsiloxane) (PDMS) prepolymers has been investigated as a pathway to novel soft PDMS networks, based on commercially available starting materials was developed. Through a fast and efficient two‐step cross‐linking reaction highly flexible PDMS elastomers were prepared.
Phosphate‐Triggered Self‐Assembly of N‐[(Uracil‐5‐yl)methyl]urea: A Minimalistic Urea‐Derived Hydrogelator
Authors: Kleinsmann Alexander J. , Weckenmann Nicole M. , Nachtsheim Boris J. 
Published: July 2014

AbstractN‐[(Uracil‐5‐yl)methyl]urea is reported as a minimalistic low‐molecular‐weight hydrogelator (LMWHG). The unusual phosphate‐induced assembly of this compound has been thoroughly investigated by IR, UV/Vis, and NMR spectroscopy, electron microscopy, and rheological experiments. This rare example of an anion‐triggered urea‐based LMWHG is the first example of a pyrimidine‐ and urea‐containing molecule that can be forced into self‐assembly in aqueous solution without additional aromatic or lipophilic groups. The gelator/phosphate ratio within the hydrogel was successfully determined by 31P MAS NMR spectroscopy. The hydrogel exhibits a very fast and repeatable self‐healing property, and remarkable G′ values. The viscoelastic properties of the hydrogel can easily be tuned by variation of the phosphate ratio.