bluuebunny/crossref_metadata_2025 huggingface dataset:
Manipulation of Intracellular Auxin in a Single Cell by Light with Esterase‐Resistant Caged Auxins
Authors: Kusaka Naoyuki , Maisch Jan , Nick Peter , Hayashi Ken‐ichiro , Nozaki Hiroshi
Published: July 2009

Auxin, a plant hormone, is polar transported from its site of production. This auxin polar transport system establishes an auxin gradient in plant tissue that is necessary for proper plant development. Therefore, the spatial effect of the auxin gradient on plant development is highly important for the understanding of plant auxin responses. Herein we report the design, syntheses and biological properties of esterase‐resistant caged auxins. The conventional caging group, 2‐nitrobenzyl ester, was found to be enzymatically hydrolyzed in plant cells and released original auxin without photolysis. The esterase‐resistant caging group, (2,5‐dimethoxyphenyl)(2‐nitrobenzyl) ester, (DMPNB) was designed to improve the stability of caged auxins. Three auxins, indole 3‐acetic acid, naphthalene 1‐acetic acid and 2,4‐dichlorophenoxy acetic acid were caged with the DMPNB caging group. DMPNB‐caged auxins were inactive within a plant cell until photolysis, but they release auxins with photoirradiation to activate auxin‐responsive gene expression. We demonstrated spatial and temporal control of intracellular auxin levels with photoirradiation by using this caged auxin system and were able to photocontrol the physiological auxin response in Arabidopsis plants. Additionally, the photoirradiation of DMPNB‐caged auxin within a single cell can manipulate the intracellular auxin level and triggers auxin response.
Microwaves in Heterogeneous Gas‐Phase Catalysis: Experimental and Numerical Approaches
Authors: Durka T. , Van Gerven T. , Stankiewicz A.
Published: July 2009

This review paper focuses on the effects of microwave irradiation on heterogeneous gas phase catalytic reaction systems. Both experimental and modeling approaches are discussed. The currently available methods for temperature measurements in the microwave heating of solid particles are critically examined. The existence of microwave‐created temperature gradients in beds of solid particles is discussed. The not fully established mechanism of catalyst (nano)particle heating and imperfect temperature measurement techniques implicate that different effects are often observed and contradictory conclusions are drawn. For further progress here, the development of accurate and possibly non‐invasive techniques for local temperature measurements under microwave irradiation is needed.
Electroactive Linear–Hyperbranched Block Copolymers Based on Linear Poly(ferrocenylsilane)s and Hyperbranched Poly(carbosilane)s
Authors: Wurm Frederik , Hilf Stefan , Frey Holger
Published: July 2009

A convenient two‐step protocol is presented for synthesis of linear‐hyperbranched diblock copolymers consisting of a linear, organometallic poly(ferrocenylsilane) (PFS) block and hyperbranched poly(carbosilane) (hbPCS) segments. Linear PFS diblock copolymers were synthesized through photolytic ring‐opening polymerization of dimethyl[1]silaferrocenophane as the first block and methylvinyl[1]silaferrocenophane as the second. These block copolymers served as polyfunctional cores in a subsequent hydrosilylation polyaddition of different silane‐based AB2 monomers. Three AB2 monomers (methyldiallylsilane; methyldiundecenylsilane, and ferrocenyldiallylsilane) were investigated; they introduced structural diversity to the hyperbranched block and showed variable reactivity for the hydrosilylation reaction. In the case with the additional ferrocene moiety in the ferrocenyldiallylsilane monomer, an electroactive hyperbranched block was generated. No slow monomer addition was necessary for molecular‐weight control of the hyperbranching polyaddition, as the core had much higher functionality and reactivity than the carbosilane monomers. Different block ratios were targeted and hybrid block copolymers with narrow polydispersity (<1.2) were obtained. All the resulting polymers were investigated and characterized by size exclusion chromatography, NMR spectroscopy, cyclic voltammetry, and TEM, and exhibited strongly anisotropic aggregation.
Synthesis of Organoplatinum Poly(dendrimer)s: Pronounced Effect of Size and Geometry of Small Organoplatinum Linkers on the Copolymerization Efficiency with Bifunctional Dendritic Macromonomers
Authors: Cheung Siu‐Yin , Chow Hak‐Fun
Published: July 2009

The copolymerizations of two series of surface functionalized bis(acetylene) G1–G3 dendrimers, one (S‐Gn) having a structural rigid skeleton and the other (L‐Gn) a relatively more flexible architecture, with two platinum linkers, cis‐[(Et2PCH2CH2PEt2)PtCl2] (2) and [Cl(Et3P)2Pt‐CC‐p‐C6H4‐]2 (3) were investigated. For both series of dendrimers, only linear and/or cyclic oligomers were formed when the cis‐platinum linker 2 was used. However, high molecular weight (100–200 kD) organoplatinum poly(dendrimer)s were obtained from both series when the elongated linear rod‐liked platinum linker 3 was employed and the formation of cyclic oligomers was greatly suppressed for both the structural rigid S‐Gn and the structural flexible L‐Gn series. These results are in sharp contrast to our earlier findings (S.‐Y. Cheung, H.‐F. Chow, T. Ngai, X. Wei, Chem. Eur. J. 2009, 15, 2278–2288) obtained by using a shorter linear platinum linker trans‐[Pt(PEt3)2Cl2] (1), where a larger amount of cyclic oligomers was formed from the structural flexible L‐Gn dendrimers. A model was proposed to rationalize how the geometry and size of the platinum linker could control the copolymerization behaviours of these dendritic macromonomers.
Rational Design, Synthesis, and Optical Properties of Film‐Forming, Near‐Infrared Absorbing, and Fluorescent Chromophores with Multidonors and Large Heterocyclic Acceptors
Authors: Luo Min , Shadnia Hooman , Qian Gang , Du Xiaobo , Yu Dengbin , Ma Dongge , Wright James S. , Wang Zhi Yuan
Published: July 2009

A new series of film‐forming, low‐bandgap chromophores (1 a,b and 2 a,b) were rationally designed with aid of a computational study, and then synthesized and characterized. To realize absorption and emission above the 1000 nm wavelength, the molecular design focuses on lowering the LUMO level by fusing common heterocyclic units into a large conjugated core that acts an electron acceptor and increasing the charge transfer by attaching the multiple electron‐donating groups at the appropriate positions of the acceptor core. The chromophores have bandgap levels of 1.27–0.71 eV, and accordingly absorb at 746–1003 nm and emit at 1035–1290 nm in solution. By design, the relatively high molecular weight (up to 2400 g mol−1) and non‐coplanar structure allow these near‐infrared (NIR) chromophores to be readily spin‐coated as uniform thin films and doped with other organic semiconductors for potential device applications. Doping with [6,6]‐phenyl‐C61 butyric acid methyl ester leads to a red shift in the absorption only for 1 a and 2 a. An interesting NIR electrochromism was found for 2 a, with absorption being turned on at 1034 nm when electrochemically switched (at 1000 mV) from its neutral state to a radical cation state. Furthermore, a large Stokes shift (256–318 nm) is also unique for this multidonor–acceptor type of chromophore, indicating a significant structural difference between the ground state and the excited state. Photoluminescence of the film of 2 a was further probed at variable temperatures and the results strongly suggest that the restriction of bond rotations certainly helps to diminish non‐radiative decay and thus enhance the luminescence of these large chromophores.
Hybrid Conjugated Organic Oligomers Consisting of Oligodiacetylene and Thiophene Units: Synthesis and Optical Properties
Authors: Pilzak Gregor S. , van Gruijthuijsen Kitty , van Doorn Reindert H. , van Lagen Barend , Sudhölter Ernst J. R. , Zuilhof Han
Published: July 2009

Novel and highly soluble hybrid conjugated organic oligomers consisting of oligodiacetylene and thiophene units have been synthesized in high purity through iterative and divergent approaches based on a sequence of Sonogashira reactions. The series of thiophene‐containing oligodiacetylenes (ThODAs) and homocoupled ThODAs (HThODAs) show—both in solution and in the solid state—a strong optical absorption, which is progressively red shifted with increasing chain length. The linear correlation of the absorption maximum (λAmax) with the inverse of conjugation length (CL=number of double and triple bonds) shows that the effective conjugation length of this system is extended up to at least CL=20. Furthermore, absorption measurements of dropcast thin films display not only a bathochromic shift of the absorption maxima but also a higher wavelength absorption, which is attributed to increased π–π interactions. The wavelength of the maximum fluorescence emission (λEmax) also increases with CL, and emission is maximal for oligomers with CL=7–12 (fluorescence quantum yield ΦF=∼0.2). Both longer and shorter oligomers display marginal emission. The calculated Stokes shifts of these planar materials are relatively large (0.4 eV) for all oligomers, and likely due to excitation to the S2 state, thus suggesting that the presence of enyne moieties dominates the ordering of the lowest excited states. The fluorescence lifetimes (τF) are short (τF,max=≪1 ns) and closely follow the tendency obtained for the fluorescence quantum yield. The anisotropy lifetimes show a near‐linear increase with CL, in line with highly rigid oligomers.
Metal‐Catalyzed Cyclization of β‐ and γ‐Allenols Derived from D‐Glyceraldehyde—Synthesis of Enantiopure Dihydropyrans and Tetrahydrooxepines: An Experimental and Theoretical Study
Authors: Alcaide Benito , Almendros Pedro , del Campo Teresa Martínez , Soriano Elena , Marco‐Contelles José L.
Published: July 2009

Regiocontrolled metal‐catalyzed preparations of enantiopure dihydropyrans and tetrahydrooxepines have been synthesized starting from β‐ and γ‐allenols derived from D‐glyceraldehyde. The PdII‐catalyzed cyclizative coupling reactions of β‐allenols 1 a and 1 b with allyl bromide effectively afforded enantiopure tetrafunctionalized dihydropyrans through a 6‐endo oxycyclization protocol, whereas the gold‐, platinum‐, and palladium‐mediated heterocyclization of γ‐allenol 2 furnished tetrahydrooxepines 13–16 through regioselective 7‐endo‐trig oxycyclization reactions. Moreover, density functional calculations were performed to predict the regioselectivity of the γ‐allenol cycloetherification to tetrahydrooxepines on the basis of both the tether nature and characteristics of the metals, and to gain an insight into the mechanism of the oxycyclization reactions.
Fullerene Derivatives Functionalized with Diethylamino‐Substituted Conjugated Oligomers: Synthesis and Photoinduced Electron Transfer
Authors: Gégout Aline , Nierengarten Jean‐François , Delavaux‐Nicot Béatrice , Duhayon Carine , Saquet Alix , Listorti Andrea , Belbakra Abdelhalim , Chiorboli Claudio , Armaroli Nicola
Published: July 2009

Diethylamino‐substituted oligophenylenevinylene (OPV) building blocks have been prepared and used for the synthesis of two [60]fullerene–OPV dyads, F‐D1 and F‐D2, which exhibit different conjugation length of the OPV fragments. The electrochemical properties of these acceptor–donor dyads have been studied by cyclic voltammetry. The first reduction is always assigned to the fullerene moiety and the first oxidation centered on the diethylaniline groups of the OPV rods, thus making these systems suitable candidates for photoinduced electron transfer. Both the OPV and the fullerene‐centered fluorescence bands are quenched in toluene and benzonitrile, which suggests the occurrence of photoinduced electron transfer from the amino‐substituted OPVs to the carbon sphere in the dyads in both solvents. By means of bimolecular quenching experiments, transient absorption spectral fingerprints of the radical cationic species are detected in the visible (670 nm) and near‐IR (1300–1500 nm) regions, along with the much weaker fullerene anion band at λmax=1030 nm. Definitive evidence for photoinduced electron transfer in F‐D1 and F‐D2 comes from transient absorption measurements. A charge‐separated state is formed within 100 ps and decays in less than 5 ns.
Construction of the Active Site of Metalloenzyme on Au NC Micelles
Authors: ZHANG Zhiming , FU Qiuan , HUANG Xin , XU Jiayun , LIU Junqiu , SHEN Jiacong
Published: July 2009

For developing an efficient nanoenzyme system with self‐assembly strategy, gold nanocrystal micelles (Au NC micelles) with inserted catalytic Zn(II) centers were constructed by self‐assembly of a catalytic ligand [N,N‐bis(2‐aminoethyl)‐N′‐dodecylethylenediamine] Zn(II) complexes (Zn(II)L) on the surface of Au NC via hydrophobic interaction. The functionalized Au NC micelles acted as an excellent nanoenzyme model for imitating ribonuclease. The catalytic capability of the Au NC micelles was evaluated by accelerating the cleavage of 2‐hydroxypropyl p‐nitrophenyl phosphate (HPNP). These functionalized Au NC micelles exhibited considerable ribonuclease‐like activities by a factor of 4.9×104 (kcat/kuncat) for the cleavage of HPNP in comparison to the spontaneous cleavage of HPNP at 37°C. The catalytic capability of the functionalized Au NC micelles can be considerably compared to other models reported previously as nanoenzymes under the comparable conditions.
Highly Efficient Conjugate Addition of Amines to Electron Deficient Alkenes Catalyzed by KF Supported on Metal Oxides
Authors: LIANG Xuezheng , ZHANG Jing , BAO Shaohua , YANG Jianguo
Published: July 2009

A novel efficient procedure has been developed for the conjugate addition of amines to electron deficient alkenes. A series of KF supported on different carriers have been synthesized for the conjugate addition amines to alkenes. After optimizing the reaction conditions, KF/MgO was chosen as the most efficient catalyst for the reactions. The results showed that the catalyst was very efficient for the conjugate addition of amines to electron deficient alkenes with excellent yields in several minutes. Operational simplicity, no need of any solvent, low cost of the catalyst used, high yields, reusability, excellent chemoselectivity and wide applicability are the key features of this methodology.
Thermodynamic Study on Complex of Terbium with Glycine Tb(Gly)2Cl3·3H2O
Authors: LIU Beiping , TAN Zhicheng , ZHANG Jingnan , LÜ Xuechuan , ZHANG Dashun , CHEN Zhengan
Published: July 2009

A terbium complex with glycine Tb(Gly)2Cl3·3H2O was synthesized and its IR spectrum was determined. The heat capacity of the complex was measured with a high‐precision automatic adiabatic calorimeter over the temperature range from 81 to 378 K. From 170 to 247 K, two solid‐solid phase transitions occurred at 186.054 and 244.063 K, respectively. Thermal decomposition of the complex was studied by thermogravimetric (TG) techniques and a possible mechanism for the decomposition was suggested. By isoperibol solution‐reaction calorimetry, the standard molar enthalpy of formation of Tb(Gly)2Cl3·3H2O was derived to be − (3109.5±3.1) kJ·mol−1.
Theoretical Investigation on the One‐ and Two‐photon Absorption Properties of Porphyrin‐thiophene Chromophores
Authors: LI Wenchao , FENG Jikang , REN Aimin , ZHANG Xiangbiao , SUN Chiachung
Published: July 2009

Two series of porphyrin‐thiophene chromophores were theoretically studied that exhibit large two‐photon absorption cross‐section in the visible region. The density functional theory (DFT) associated with ZINDO/SDCI methods has been used to calculate the molecular geometries, electronic structures, one‐photon and two‐photon absorption properties. The results show that the number of thiophene units affects the properties of one‐photon absorption (OPA) and two‐photon absorption (TPA). Porphyrin‐thiophene chromophores featuring two or three thiophene units have wide TPA response ranges; they can be applied to many nonlinear optical areas, such as optical limiting. Intervening ethynyl unit is beneficial to extend the conjugated pathway, and increase the two‐photon absorption cross‐section. At the same time, the OPA and TPA wavelengths are bathochromically shifted. From viewpoint of the high transparency and large nonlinear optical response, porphyrin‐thiophene chromophores will be promising TPA materials.
Syntheses, Structure, Magnetic Properties and 57Fe M?ssbauer Spectroscopies of Two Iron(II) Complexes: Room‐temperature Spin Crossover Behavior Observed in [Fe(dpq)(MePy)2(NCS)2]
Authors: TAO Jianqing , GU Yunlan , ZHOU Xinhui , GU Zhiguo , ZUO Jinglin , YOU Xiaozeng
Published: July 2009

Two new complexes [Fe(dpq)(MePy)2(NCS)2] (1) and [Fe(Medpq)(MePy)2(NCS)2] (2) (dpq=2‐dipyrido[3,2‐f: 2′,3′‐h]quinoxaline, Medpq=2‐methyldipyrido[3,2‐f:2′,3′‐h]quinoxaline, MePy=4‐methylpyridine) have been synthesized. The crystal structure of 2 was characterized by X‐ray diffraction at room temperature. It crystallizes in orthorhombic space group I212121, with a=15.057(3) Å, b=14.569(3) Å, c=13.180(3) Å, α =90.00°, β=90.00°, γ=90.00°, and V=2891.2(11) Å3. The distorted [FeN6] octahedron in 2 is formed by six nitrogen atoms from Medpq, two trans‐MePy molecules and two cis‐NCS− anions. Variable‐temperature magnetic susceptibilities and M?ssbauer spectroscopies of 1 and 2 reveal the occurrence of a gradual spin transition. The transition for 1 spans the 200–450 K temperature range with a T1/2 of 340 K, while for 2, the transition in low temperature is incomplete.
Sol‐gel Preparation of CNT/ZnO Nanocomposite and Its Photocatalytic Property
Authors: WANG Xuejing , YAO Shuwen , LI Xiaobo
Published: July 2009

Using carbon nanotubes (CNT) as templete, CNT/ZnO nanocomposite was prepared by a sol‐gel method. Its structure was characterized by XRD, IR and TEM. The UV absorbing properties were detected by a UV spectrophotometer. Photo degradation of methyl red in aqueous solution was investigated by using CNT/ZnO nanocomposite as photocatalyst. The results showed that the nanocomposite was composed of carbon nanotubes coated evenly by ZnO particles, with a diameter of 50–60 nm. UV‐vis spectra indicated that the as‐prepared CNT/ZnO nanocomposite had absorption of visible light as well as ultraviolet light. 60% CNT‐added nanocomposite had the highest degradation rate for methyl red under the sunlight irradiation.
Resonance Scattering Spectral Determination of Trace Penicillin G Using Immunonanogold‐HAuCl4‐NH2OH Catalytic Reaction
Authors: WEN Guiqing , LI Yan , LIANG Aihui , JIANG Zhiliang
Published: July 2009

Both nanogold and immunonanogold exhibit catalytic effect on the slow reaction of HAuCl4‐NH2OH to form gold particles which displayed a resonance scattering (RS) peak at 580 nm. Using hapten penicillin G (PG) as a model, the nanogold in size of 9 nm was used to label rabbit anti‐penicillin G antisera (RAPG) to obtain an immunonanogold probe (AuRAPG) for PG. The PG was combined with AuRAPG to form the immunocomplex and bigger nanogold clusters. After centrifugation, the excess AuRAPG in the supernatant exhibited catalytic effect on the reaction of HAuCl4‐NH2OH, and the RS intensity at 580 nm (I580 nm) was enhanced greatly. With the addition of PG, the I580 nm decreased accordingly. Under the optimal conditions, the decreased intensity ΔI580 nm was proportional to the PG concentration in the range of 0.15–225 ng/mL, with a detection limit of 0.05 ng/mL for PG.
Generation of Pd Nanoparticles in situ from PdCl2 in TBAF: An Efficient and Reusable Catalytic System for the Suzuki‐Miyaura Reaction under Ligand‐ and Solvent‐free Conditions
Authors: TAO Liming , XIE Yexiang , DENG Chenliang , LI Jinheng
Published: July 2009

Pd nanoparticles were generated in situ from PdCl2 in TBAF (n‐Bu4NF), which displayed high efficiency for the Suzuki‐Miyaura cross‐coupling reaction. In the presence of PdCl2 and TBAF, a variety of aryl halides were coupled with arylboronic acids smoothly in moderate to good yields. Moreover, the PdCl2/TBAF system could be recovered and reused several times in the Suzuki‐Miyaura reaction, and aryl bromides could be consumed completely by arylboronic acids in about 15–60 min. It is noteworthy that these reactions were conducted under solvent‐free, ligand‐free and reusable conditions. Mechanism for the PdCl2/TBAF‐catalyzed reactions was also discussed.
Synthesis and Cytotoxicity of Derivatives of Fluorouracil Conjugated with Three‐membered Ring
Authors: WANG Le , ZHANG Yunxiao , TAO Jingchao
Published: July 2009

A novel series of 3‐membered ring fluorouracil conjugates including cyclopropylmethyl fluorouracil and (2,3‐epoxypropyl) fluorouracil conjugates were synthesized via selective protection, and their structures were confirmed by IR, 1H NMR and HRMS. Cytotoxicities in vitro of these conjugates were evaluated. Compounds 7, 8, 12 and 13 have shown cytotoxicities against Ec9706 cells in different degrees.
A Concise Synthesis of (±)‐Yaequinolone A2
Authors: LI Xinyun , HUO Xing , LI Junpeng , SHE Xuegong , PAN Xinfu
Published: July 2009

A concise total synthesis of (±)‐yaequinolone A2 (2), a 2‐quinolone alkaloid, has been accomplished through 6 steps from anthranilic acid with an overall yield of 27.8%. The synthetic strategy exploits highly diastereoselective intramolecular aldol addition of the MOM protected α‐hydroxyanilide 7 as the key step.
A Novel Palladium‐catalyzed Amination of Aryl Halides with Amines Using rac‐P‐Phos as the Ligand
Authors: CHEN Huansheng , WANG Quanrui , TAO Fenggang
Published: July 2009

An efficient palladium‐catalyzed amination of aryl halides with amines, using rac‐P‐Phos as the ancillary ligand and Pd(OAc)2 as the palladium source is developed. The ligand and all of the synthetic intermediates are stable to air and moisture, allowing the easy handling. The catalyst system performed well for a large number of different substrate combinations in 80–110°C to furnish aromatic amines in high yields.
Synthetic Strategy of o‐Hydroxyphenyl(ethynyl)phosphinates
Authors: XIE Liang , DING Yi , WANG Yong , DING Yixiang
Published: July 2009

A useful and practical route to the synthesis of o‐hydroxyphenyl(ethynyl)phosphinates is presented, which are useful intermediates because of their multiple functional groups.
A Convenient Method to Construct Chroman Skeleton: Asymmetric Synthesis of (−)‐4′‐Hydroxy‐7‐methoxyflavane
Authors: XU Boyan , XUE Jijun , ZHANG Huabing , LI Ying
Published: July 2009

The first enantioselective synthesis of a naturally occurring 4′‐hydroxy‐7‐methoxyflavane was developed by an asymmetric reduction and a microwave‐assistant aromatic C–O bond formation to construct the benzopyran skeleton. Key features of this method include its brevity, its preserved stereochemical integrity and two different synthetic routes to choose.
A New Route to Biaryl Ketones via Carbonylative Suzuki Coupling Catalyzed by MCM‐41‐supported Bidentate Phosphine Palladium(0) Complex
Authors: ZHENG Guomin , WANG Pingping , CAI Mingzhong
Published: July 2009

A variety of biaryl ketones can be conveniently synthesized in good to high yields via the first heterogeneous carbonylative Suzuki coupling of arylboronic acids with aryl iodides under atmospheric pressure of carbon monoxide in the presence of a catalytic amount of MCM‐41‐supported bidentate phosphine palladium(0) complex [MCM‐41‐2P‐Pd(0)]. This polymeric palladium catalyst can be reused at least 10 times without any decrease in activity.
Regio‐specific Microbial Hydroxylation of Phytolaccagenin by Streptomyces griseus ATCC 13273
Authors: QIAN Liwu , ZHANG Jian , LIU Jihua , YU Boyang
Published: July 2009

Microbial transformation of one oleane‐type pentacyclic triterpene aglycone, phytolaccagenin (2β,3β,23‐trihydroxy‐olean‐12‐ene‐28,30‐dioic acid 30‐methyl ester) by Streptomyces griseus ATCC 13273 was investigated for developing new bioactive derivatives. A new oxidized metabolite, through the regio‐specific hydroxylation on the C‐29 methyl group, was obtained from the preparative‐scale biotransformation with a standard two‐stage fermentation protocol. The metabolite was identified as 2β,3β,23,29‐tetrahydroxy‐olean‐12‐ene‐28,30‐dioic acid 30‐methyl ester by mass and 2D‐NMR spectra.
A Second Generation of Carbamate‐Based Fatty Acid Amide Hydrolase Inhibitors with Improved Activity in vivo
Authors: Clapper Jason R. , Vacondio Federica , King Alvin R. , Duranti Andrea , Tontini Andrea , Silva Claudia , Sanchini Silvano , Tarzia Giorgio , Mor Marco , Piomelli Daniele
Published: July 2009

The fatty acid ethanolamides are a class of signaling lipids that include agonists at cannabinoid and α type peroxisome proliferator‐activated receptors (PPARα). In the brain, these compounds are primarily hydrolyzed by the intracellular serine enzyme fatty acid amide hydrolase (FAAH). O‐aryl carbamate FAAH inhibitors such as URB597 are being evaluated clinically for the treatment of pain and anxiety, but interactions with carboxylesterases in liver might limit their usefulness. Here we explore two strategies aimed at overcoming this limitation. Lipophilic N‐terminal substitutions, which enhance FAAH recognition, yield potent inhibitors but render such compounds susceptible to attack by broad‐spectrum hydrolases and inactive in vivo. By contrast, polar electron‐donating O‐aryl substituents, which decrease carbamate reactivity, yield compounds, such as URB694, that are highly potent FAAH inhibitors in vivo and less reactive with off‐target carboxylesterases. The results suggest that an approach balancing inhibitor reactivity with target recognition produces FAAH inhibitors that display significantly improved drug‐likeness.
The Relevance of Polar Surface Area (PSA) in Rationalizing Biological Properties of Severalcis‐Diamminemalonatoplatinum(II) Derivatives
Authors: Caron Giulia , Ermondi Giuseppe , Gariboldi Marzia B. , Monti Elena , Gabano Elisabetta , Ravera Mauro , Osella Domenico
Published: July 2009

A panel of sixcis‐diamminemalonatoplatinum(II) derivatives were designed and synthesized, and their physicochemical properties and in vitro biological activity were experimentally evaluated and studied in silico. All the complexes showed higher IC50values (≥20 μM) than those observed for cisplatin and its malonato analogue on three different human tumor cell lines, namely A2780 ovarian carcinoma, A549 lung carcinoma, and MCF‐7 breast carcinoma. In silico studies revealed that polar surface area (PSA) is the best descriptor to explain the poor biological activity observed for this series of new compounds, which in turn is likely due to poor cellular uptake. This finding is in line with general rules that assign a major role to PSA in characterizing the transport properties of drugs, in the actual case of antiproliferative metallopharmaceuticals.
2,3‐Dihydro‐1‐Benzofuran Derivatives as a Series of Potent Selective Cannabinoid Receptor 2 Agonists: Design, Synthesis, and Binding Mode Prediction through Ligand‐Steered Modeling
Authors: Diaz Philippe , Phatak Sharangdhar S. , Xu Jijun , Fronczek Frank R. , Astruc‐Diaz Fanny , Thompson Charles M. , Cavasotto Claudio N. , Naguib Mohamed
Published: July 2009

We recently discovered and reported a series ofN‐alkyl‐isatin acylhydrazone derivatives that are potent cannabinoid receptor 2 (CB2) agonists. In an effort to improve the druglike properties of these compounds and to better understand and improve the treatment of neuropathic pain, we designed and synthesized a new series of 2,3‐dihydro‐1‐benzofuran derivatives bearing an asymmetric carbon atom that behave as potent selective CB2agonists. We used a multidisciplinary medicinal chemistry approach with binding mode prediction through ligand‐steered modeling. Enantiomer separation and configuration assignment were carried out for the racemic mixture for the most selective compound, MDA7 (compound18). It appeared that theS enantiomer, compound MDA104 (compound33), was the active enantiomer. Compounds MDA42 (compound19) and MDA39 (compound30) were the most potent at CB2. MDA42 was tested in a model of neuropathic pain and exhibited activity in the same range as that of MDA7. Preliminary ADMET studies for MDA7 were performed and did not reveal any problems.
Esophagectomy compared with chemoradiation for early stage esophageal cancer in the elderly
Authors: Abrams Julian A. , Buono Donna L. , Strauss Joshua , McBride Russell B. , Hershman Dawn L. , Neugut Alfred I.
Published: July 2009

BACKGROUND:

Esophagectomy has been the traditional treatment of choice for early stage esophageal cancer. However, esophagectomy is associated with high mortality and morbidity in the elderly, and these patients often receive chemoradiation instead. The authors of this report compared outcomes of esophagectomy versus chemoradiation in a population‐based sample of elderly patients with early stage esophageal cancer.

METHODS:

The Surveillance, Epidemiology, and End Results‐Medicare database was used to identify patients aged ≥65 years who were diagnosed with stage I or II esophageal cancer from 1991 to 2002. The associations of treatment with esophagectomy or chemoradiation were assessed along with demographic and clinical variables. A survival analyses was performed to compare outcomes with treatment modality and was adjusted for potential confounders.

RESULTS:

Seven hundred thirty patients with stage I or II esophageal cancer were identified who underwent esophagectomy (n = 341; 46.7%) or chemoradiation (n = 389; 53.3%). Older age, squamous cell histology, and lower socioeconomic status were associated with increased odds of receiving chemoradiation. In multivariate analyses, chemoradiation was associated with worse disease‐specific survival (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.64‐2.64) and overall survival (HR, 1.92; 95%CI, 1.58‐2.34). The receipt of chemoradiation was associated with worse survival for patients with adenocarcinoma (HR, 3.01; 95%CI, 2.24‐4.04), but there was no significant difference for patients with squamous cell carcinoma (HR, 1.33; 95%CI, 0.98‐1.80).

CONCLUSIONS:

Compared with chemoradiation, esophagectomy may be associated with improved survival for early stage esophageal cancer in the elderly. The current results suggest that there also may be a subset of patients with squamous cell carcinoma for whom chemoradiation is adequate therapy. A randomized trial would be useful to determine the optimal treatment for elderly patients with early stage esophageal cancer. Cancer 2009. © 2009 American Cancer Society.
Lambda calculus as a workflow model
Authors: Kelly Peter M. , Coddington Paul D. , Wendelborn Andrew L.
Published: July 2009

Data‐oriented workflows are often used in scientific applications for executing a set of dependent tasks across multiple computers. We discuss how these can be modeled using lambda calculus, and how ideas from functional programming are applicable in the design of workflows. Such an approach avoids the restrictions often found in workflow languages, permitting the implementation of complex application in logic and data manipulation. This paper explains why lambda calculus is an appropriate model for workflow representation, and how a suitably efficient implementation can provide a wide range of capabilities to developers. The presented approach also permits high‐level workflow features to be implemented at user level, in terms of a small set of low‐level primitives provided by the language implementation. Copyright © 2009 John Wiley & Sons, Ltd.
Decentralized guaranteed cost control for uncertain large‐scale systems using additive control gain
Authors: Mukaidani Hiroaki , Kimoto Minoru
Published: July 2009

This paper investigates an application of additive control gain to the guaranteed cost control (GCC) problem of decentralized robust control for a class of discrete‐time uncertain large‐scale systems. Based on the Linear Matrix Inequality (LMI) design approach, a class of decentralized local fixed state feedback controllers with additive control gain is established. The novel contribution of this paper is that multiobjective control is attained by using the additive control gain. Although the additive control gain is included in the uncertain large‐scale systems, the closed‐loop system is asymptotically stable. In order to demonstrate the efficiency of our proposed controller, using the fuzzy logic control as the additive control gain, the simple numerical example is given. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 169(3): 18–32, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20726
Influence of catalyst and gas diffusion layer degradation on flooding in pefc
Authors: Hiramitsu Yusuke , Hayashi Yoshihiko , Kobayashi Kenji , Hori Michio
Published: July 2009

With respect to polymer electrolyte fuel cells (PEFC), degradation of the catalyst and gas diffusion layers, which are parts of the membrane electrode assembly (MEA), and its influence on electrode flooding were investigated. High‐humidity operation is desirable for high performance of a PEFC, because the proton exchange membrane and ionomer at the catalyst layer must hold a large amount of water. Additionally, high gas utilization is necessary for high system efficiency. However, under these conditions, the cell performance is significantly degraded by water flooding of the electrodes. A PEFC single cell was operated at 0.3 A/cm2 at high humidity for 10,000 h, and the cell performance was evaluated in terms of the cell potential, cell resistance, IV characteristics, crossover rate, effective chemical surface area, and oxygen gain, in order to determine the parts of the cell that play a dominant role in cell degradation. Degradation of gas diffusivity was found to dominate the degradation of cell performance, and it was found to occur mainly in the catalyst layer rather than in the gas diffusion layer. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 169(3): 10–17, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20899
An engine control systems design for low‐emission vehicles by generalized predictive control based on identified model
Authors: Hashimoto Seiji , Okuda Hiroyuki , Okada Yasushi , Adachi Shuichi , Niwa Shinji , Kajitani Mitsunobu
Published: July 2009

Conservation of the environment has become critical to the automotive industry. Recently, requirements for on‐board diagnostic and engine control systems have been strictly enforced. In the present paper, in order to meet the requirements for low‐emission vehicles, a novel method for construction of the air‐fuel ratio (A/F) control system is proposed. The method of construction of the system is divided into two steps. The first step is to design the A/F control system for the engine based on an open loop design. The second step is to design the A/F control system for the catalyst system. The design method is based on generalized predictive control in order to assure robustness to open loop control as well as model uncertainty. The effectiveness of the proposed A/F control system is verified through experiments using full‐scale products. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 169(3): 47–55, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20907
An evaluation of amorphous transformers using the load curve pattern model for a pole transformer
Authors: Takagi Masaaki , Yamamoto Hiromi , Yamaji Kenji
Published: July 2009

Energy loss in transformers is composed of no‐load loss and load loss. The no‐load loss of amorphous transformers, which have amorphous metal core, could be reduced by about 70% compared with traditional silicon steel transformers. If the electrical utilities adopted amorphous transformers as pole transformers, major energy savings and CO2 emissions reduction could be achieved. However, amorphous transformers have the disadvantages of high capital cost and high load loss parameters compared with traditional transformers. The economic efficiency of transformers is evaluated by the Total Ownership Cost (TOC). The TOC encompasses both the capital cost and the energy loss cost, which is calculated from the load curve. Therefore, we propose a load curve pattern model for pole transformers to evaluate the energy‐saving effect and the economic efficiency of amorphous transformers. Simulation results show that the no‐load loss accounts for a large share of the total loss; hence, reduction of the no‐load loss is more effective than reduction of load loss in achieving energy saving. As a result, amorphous pole transformers are the most suitable for pole transformers. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 169(3): 1–9, 2009; Published online in Wiley InterScience (www. interscience.wiley.com). DOI 10.1002/eej.20924
Fetal BM‐derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells
Authors: Guo Zhenxing , Zheng Cuiling , Chen Zhenping , Gu Dongsheng , Du Weiting , Ge Jing , Han Zhongchao , Yang Renchi
Published: July 2009

Th type 17 (Th17) cells have been identified as a proinflammatory T‐cell subset. Here, we investigated the regulation of human Th17 cells by fetal BM‐derived mesenchymal stem cells (FBM‐MSC). We cocultured FBM‐MSC with human PBMC or CD4+ T cells from healthy donors. FBM‐MSC significantly suppressed the proliferation of CD4+ T cells stimulated by PHA and recombinant IL‐2. Significantly higher levels of IL‐17 were observed in FBM‐MSC cocultured with either PBMC or CD4+ T cells than that in PBMC cultured alone or CD4+ T cells cultured alone. Flow cytometry analysis showed that the percentage of Th17 cells in coculture of FBM‐MSC and CD4+ T cells was significantly higher than that in CD4+ T‐cell cultured alone. FBM‐MSC did not express IL‐17 protein. Consistent with the augmentation of Th17 cells, significantly higher levels of IL‐6 and IL‐1 were observed in coculture of FBM‐MSC and CD4+ T cells than that in CD4+ T‐cell culture, while the levels of IL‐23 were similar between FBM‐MSC + PBMC coculture and PBMC alone, or FBM‐MSC + CD4+ T‐cell and CD4+ T‐cell alone. The presence of FBM‐MSC decreased the percentage of Th1 cells, but minimally affected the expansion of CD4+CD25+ T cells. In conclusion, our data demonstrate for the first time that FBM‐MSC promote the expansion of Th17 cells and decrease IFN‐γ‐producing Th1 cells. These data suggest that IL‐6 and IL‐1, instead of IL‐23, may be partly involved in the expansion of Th17 cells.
Allogeneic induced human FOXP3+IFN‐γ+ T cells exhibit selective suppressive capacity
Authors: Stroopinsky Dina , Avivi Irit , Rowe Jacob M. , Avigan David , Katz Tamar
Published: July 2009

Human induced CD4+CD25+ T cells have been shown to express FOXP3, similar to naturally occurring Treg cells (nTreg). However, the suppressive capacity of these cells is still under debate. The current study was designed to investigate functional characteristics of CD25+FOXP3+ derived from CD25− T cells. Stimulation of CD25− PBMC with allogeneic PBMC resulted in production of CD4+CD25high T cells. This process was more rapid and prominent when highly mature DC were used for stimulation. The resultant CD4+CD25high population concurrently exhibited regulatory markers FOXP3, CTLA‐4, GITR, and inflammatory cytokines IL‐2 and IFN‐γ. These human‐induced FOXP3+IFN‐γ+ T cells were shown, for the first time, to markedly inhibit alloreactive T‐cell expansion, similar to nTreg. However, in contrast to nTreg, the induced CD4+CD25+FOXP3+ cells did not suppress proliferation against a third party donor stimulus or CMV. This suggested that the cell population possessed a more selective suppressive capacity targeted against the original stimulus only. The induced human CD4+CD25+FOXP3+ subset derived from CD25− T cells, while expressing inflammatory cytokines, exhibits a suppressive cell contact‐dependent effect, restricted against T cells responding to the original stimulus. Such unique properties suggest that these cells are potentially ideal for the use as post‐transplant GVH disease prophylaxis.
TLR8‐mediated activation of human monocytes inhibits TL1A expression
Authors: Saruta Masayuki , Michelsen Kathrin S. , Thomas Lisa S. , Yu Qi T. , Landers Carol J. , Targan Stephan R.
Published: July 2009

TLR play important roles in inflammation and innate immune response to pathogens. TLR8 recognizes ssRNA and induces NF‐κB via MyD88 signaling. TL1A is a member of the TNF superfamily that markedly enhances IFN‐γ production by IL‐12/IL‐18‐stimulated peripheral and mucosal CD4+ T cells. TL1A expression is increased in the mucosa of patients with inflammatory bowel disease and is considered a key mediator of Crohn's disease (CD). We have previously shown that TL1A is strongly induced by immune complexes (IC) but not TLR ligands in antigen‐presenting cells. However, a potential interaction between these pro‐inflammatory signaling pathways has not been investigated. IC‐induced TL1A expression of monocytes was potently inhibited by a TLR8 or TLR7/8 ligand (R848) in a dose‐dependent manner. Furthermore, when co‐cultured with CD4+ T cells, TLR8 ligands inhibited TL1A production, resulting in almost complete inhibition of IFN‐γ production by the CD4+ T cells. Furthermore, we demonstrate that IFN‐α is not required for this suppressive effect by TLR8 signaling. Our data demonstrate for the first time a direct interaction between TLR and TL1A signaling pathways. TLR8 activation may be an important, novel pathway for targeted treatment of Th1‐mediated diseases, such as CD.
Promoting MΦ transepithelial migration by stimulating the epithelial cell P2Y2 receptor
Authors: Langlois Christine , Gendron Fernand‐Pierre
Published: July 2009

In intestine, neutrophils are recruited in response to bacterial infiltration and their anti‐cellular activities contribute to inflammatory bowel diseases. In contrast, little is known regarding the recruitment of MΦ to the intestinal epithelium. Extracellular adenosine and uridine 5′‐triphosphate (ATP and UTP) can function as leukocyte chemoattractants. We investigated the effects of these nucleotides on the ability of intestinal epithelial cells (IEC) to promote MΦ transepithelial migration and adhesion. ATP and UTP promoted the migration of neutrophil‐like PLB‐985 cells and MΦ across a Caco‐2 monolayer. The MΦ‐like U‐937 cells adhered to nucleotide‐stimulated IEC monolayers. In mice with intestinal inflammation, there were infiltrating CD68+ MΦ in the colonic epithelium and CD68+ MΦ present at the apical surface of colonocytes. We determined that ATP and UTP activated the P2Y2 receptor P (P2Y2R) to increase ICAM‐1 expression, which mediated the adhesion of MΦ to the apical surface of IEC. Intriguingly, stimulation of IEC with nucleotides did not increase the adhesion of neutrophils. However, in the presence of adherent MΦ, there was adhesion of neutrophils, suggesting that MΦ may serve as anchors for neutrophil adhesion. These studies provide insight into the inflammatory mechanisms that contribute to inflammatory bowel diseases and identify potential therapeutic targets for the treatment of gastrointestinal disorders.
Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control
Authors: Fink Katja , Ng Cedrig , Nkenfou Celine , Vasudevan Subhash G. , van Rooijen Nico , Schul Wouter
Published: July 2009

Monocytes and macrophages are target cells for dengue infection. Besides their potential role for virus replication, activated monocytes/macrophages produce cytokines that may be critical for dengue pathology. To study the in vivo role of monocytes and macrophages for virus replication, we depleted monocytes and macrophages in IFN‐αβγR knockout mice with clodronate liposomes before dengue infection. Although less virus was first recovered in the draining LN in the absence of macrophages, monocyte/macrophage depletion eventually resulted in a ten‐fold higher systemic viral titer. A massive infiltration of CD11b+CD11clowLy6Clow monocytes into infected organs was observed in parallel with increasing virus titers before viremia was controlled. Depletion of monocytes in the blood before or after local infection had no impact on virus titers, suggesting that monocytes are not required as “virus‐shuttles”. Our data provide evidence that systemic viremia is established independently of tissue macrophages present at the site of infection and blood monocytes. Instead, we demonstrate the importance of monocytes/macrophages for the control of dengue virus.
IL‐12 and type I IFN response of neonatal myeloid DC to human CMV infection
Authors: Renneson Joelle , Dutta Binita , Goriely Stanislas , Danis Bénédicte , Lecomte Sandra , Laes Jean‐François , Tabi Zsuzsanna , Goldman Michel , Marchant Arnaud
Published: July 2009

Following congenital human CMV (HCMV) infection, 15–20% of infected newborns develop severe health problems whereas infection in immunocompetent adults rarely causes illness. The immaturity of neonatal antigen presenting cells could play a pivotal role in this susceptibility. Neonatal myeloid DC were shown to be deficient in IFN‐β and IL‐12 synthesis in response to TLR triggering. We studied the response of cord and adult blood‐derived myeloid DC to HCMV infection. Neonatal and adult DC were equally susceptible to in vitro HCMV infection. Among immunomodulatory cytokines, IL‐12, IFN‐β and IFN‐λ1 were produced at lower levels by neonatal as compared with adult DC. In contrast, neonatal and adult DC produced similar levels of IFN‐α and IFN‐inducible genes. Microarray analysis indicated that among the more than thousand genes up‐ or down‐regulated by HCMV infection of myeloid DC, 88 were differently regulated between adult and neonatal DC. We conclude that neonatal and adult DC trigger a partly different response to HCMV infection. The deficient IL‐12 and mature IFN‐α production by neonatal DC exposed to HCMV are likely to influence the quality of the T lymphocyte response to HCMV infection in early life.
Natural killer cells remember: An evolutionary bridge between innate and adaptive immunity?
Authors: Sun Joseph C. , Lanier Lewis L.
Published: July 2009

Since their discovery three decades ago, NK cells have been classified as cells of the innate immune system. NK cells were shown to respond rapidly and non‐specifically to infection, and were thought to act as a functional “bridge” to sustain the early innate immune response until the later adaptive immune responses could be mounted. In light of new findings showing how NK cells possess nearly all of the features of adaptive immunity including memory, we propose the placement of NK cells as an “evolutionary bridge” between innate and adaptive immunity.
Myeloid‐derived suppressor cell activation by combined LPS and IFN‐γ treatment impairs DC development
Authors: Greifenberg Verena , Ribechini Eliana , Rößner Susanne , Lutz Manfred B.
Published: July 2009

Myeloid‐derived suppressor cells (MDSC) and DC are major controllers of immune responses against tumors or infections. However, it remains unclear how DC development and MDSC suppressor activity both generated from myeloid precursor cells are regulated. Here, we show that the combined treatment of BM‐derived MDSC with LPS plus IFN‐γ inhibited the DC development but enhanced MDSC functions, such as NO release and T‐cell suppression. This was not observed by the single treatments in vitro. In the spleens of healthy mice, we identified two Gr‐1lowCD11bhighLy‐6ChighSSClowMo‐MDSC and Gr‐1highCD11blowPMN‐MDSC populations with suppressive potential, whereas Gr‐1highCD11bhigh neutrophils and Gr‐1lowCD11bhighSSClow eosinophils were not suppressive. Injections of LPS plus IFN‐γ expanded these populations within the spleen but not LN leading to the block of the proliferation of CD8+ T cells. At the same time, their capacity to develop into DC was impaired. Together, our data suggest that spleens of healthy mice contain two subsets of MDSC with suppressive potential. A two‐signal‐program through combined LPS and IFN‐γ treatment expands and fully activates MDSC in vitro and in vivo.