bluuebunny/crossref_metadata_2025 huggingface dataset:
A Tailor‐Made Chimeric Thiamine Diphosphate Dependent Enzyme for the Direct Asymmetric Synthesis of (S)‐Benzoins
Authors: Westphal Robert , Vogel Constantin , Schmitz Carlo , Pleiss Jürgen , Müller Michael , Pohl Martina , Rother Dörte
Published: July 2014

Thiamine diphosphate dependent enzymes are well known for catalyzing the asymmetric synthesis of chiral α‐hydroxy ketones from simple prochiral substrates. The steric and chemical properties of the enzyme active site define the product spectrum. Enzymes catalyzing the carboligation of aromatic aldehydes to (S)‐benzoins have not so far been identified. We were able to close this gap by constructing a chimeric enzyme, which catalyzes the synthesis of various (S)‐benzoins with excellent enantiomeric excess (>99 %) and very good conversion.
Computational fluid dynamics analysis to effects of geometrical design and physical property on complete suspension of floating solids in stirred tanks
Authors: Qiao Shengchao , Wang Rijie , Yan Yuefei , Yang Xiaoxia
Published: July 2014

The computational fluid dynamics methodology was developed to qualitatively study effects of geometrical design and physical property on the mixing quality of floating solids in stirred tanks with an up‐pumping pitched blade turbine. The multiple reference frame approach was used to model the relative motion between rotating impeller and stationary baffles. Two important mixing parameters, power number (Np) and standard deviation (σ), were used to predict critical impeller speed (NCS) for complete suspension of floating solids and compare the mixing efficiency. Predicted results were compared with the experiment results in the open literature and were explained with published mechanisms or theories concerning solid suspension. Reasonable agreements were achieved. Copyright © 2014 Curtin University of Technology and John Wiley & Sons, Ltd.
Enhancement in pyroelectric properties of PZT‐PVA polymer nanocomposites with addition of PAA
Authors: Uma Sreekumar , Philip Jacob
Published: July 2014

Composites comprising of pyroelectric ceramics and electro‐active polymers have gained importance currently as materials for thermal sensing applications, as their unique features and relevant properties can be tailored easily. In this work nanoparticles of PZT have been embedded into PVA/PAA copolymer matrix to form 0 to 3 nanocomposites. Films of the composites are prepared following solvent cast method after dispersing ceramic nanopowder homogeneously in the copolymer matrix with different wt % of the PZT powder. Relevant properties such as dielectric constant and loss factor, pyroelectric coefficients, thermal conductivity, and specific heat capacity as well as Shore hardness have been measured. The material figures of merit for pyroelectric detection have also been determined and reported. It is found that pyroelectric sensing properties of a film of the composite with 20 wt % PZT are comparable to those of commercially used β‐PVDF film for the same application, but with a lower figure of merit. However, it provides greater mouldability and simpler processibility for the fabrication of bulk sensors and actuators. So this composite can be considered as a potential material for the design and fabrication of mouldable pyroelectric detectors and actuators. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41142.
Organic solvent nanofiltration with a Poly(dimethylsiloxane) membrane: Parameters affecting its sieving properties
Authors: Leitner Loïc , Harscoat‐Schiavo Christelle , Kapel Romain , Vallieres Cécile
Published: July 2014

In this study, retention experiments were performed to characterize the variable sieving properties of a poly(dimethylsiloxane) (PDMS) membrane in relation with operating parameters. The swelling, transmembrane pressure, and temperature are all known to impact the physicochemical properties and morphology of PDMS polymer and were therefore varied for the purposes of our retention experiments which assessed them with the homologous series of polyethylene glycols (PEGs; 200–1500 g mol−1). The objectives were twofold—first, to evaluate the capacity to induce a targeted molecular weight cutoff (MWCO) by selecting appropriate filtration conditions and second to better understand the mechanisms involved during solvent‐resistant nanofiltration with PDMS. The selected solvents or solvent/solvent mixtures used throughout this study were found to induce swelling ratios of 1.16 (ethanol/ethyl acetate: 25/75), 1.26 (ethyl acetate), 1.33 (ethyl acetate/toluene: 50/50), and 1.41 (toluene), respectively. Linear correlations were obtained between the MWCO and the swelling ratio induced by each solvent and between the MWCO and the transmembrane pressure. Pore size calculations using solvent flux and retention data confirmed the variable sieving properties of the PDMS membrane in relation to the solvent‐induced swelling and applied transmembrane pressure. In addition, the study of the solute‐transfer rate through several operating conditions showed that both diffusive and convective transports occurred for the PEG solutes and that their respective contributions appeared dependent on the variable pore size of the PDMS membrane. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41171.
Study of a nanocomposite starch–clay for slow‐release of herbicides: Evidence of synergistic effects between the biodegradable matrix and exfoliated clay on herbicide release control
Authors: Giroto Amanda S. , de Campos Adriana , Pereira Elaine I. , Cruz Camila C. T. , Marconcini José M. , Ribeiro Caue
Published: July 2014

In this article a nanocomposite based on starch gel, a renewable polymer, and montmorillonite clay (MMT) is proposed as a host system for the slow‐delivery of a hydrophobic herbicide loaded in very high contents (50% in total weight), where the nanocomposite structure controls the release by imposing diffusional barriers to the active compound. The herbicide release rate in water showed that nanocomposites presented higher retentions than the neat samples (herbicide‐loaded starch or MMT), revealing a cooperative or synergic effect between the constituents. Biodegradation essays also revealed this cooperative behavior, showing longer biodegradation periods for the nanocomposite than the pristine materials. Also, a two‐step release was noticed, where the first step was controlled by starch (short periods) and the second was played by MMT (longer times). The nanocomposite structural analysis gave evidence that the release behavior is governed by the interaction between the constituents, even at very high herbicide contents. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41188.
Preparation and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles
Authors: Campos Izabella Maria Ferreira , Santos Thiago Melo , Cunha Gabriella Maria Fernandes , Silva Kláudia Maria Machado Neves , Domingues Rosana Zacarias , da Silva Cunha Júnior Armando , de Souza Figueiredo Kátia Cecília
Published: July 2014

Dexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of −2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41199.
Nonisothermal crystallization of highly‐filled polyolefin/calcium carbonate composites
Authors: Barczewski Mateusz , Kloziński Arkadiusz , Jakubowska Paulina , Sterzyński Tomasz
Published: July 2014

Nonisothermal crystallization kinetics of highly‐filled polyolefin composites was studied by means of differential scanning calorimetry (DSC). Two types of commercial calcium carbonate based fillers (modified with stearic acid and nonmodified one) were used for our investigations. In order to evaluate the crystallization kinetics changes of composites, the Avrami theory modified by Jeziorny was used. Validity of mineral fillers modification with stearic acid has been proved by thermal analysis. Because of the suppression of the heterogeneous nucleation effect resulting from calcium carbonate with stearic acid modification, an increase in the processability of highly‐filled polyolefin cast films might occur. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41201.
Synthesis, polymerization, and properties of the allyl‐functional phthalonitrile
Authors: Zou Xingqiang , Xu Mingzhen , Jia Kun , Liu Xiaobo
Published: July 2014

A novel bisphthalonitrile monomer containing allyl groups (DBPA‐Ph) had been synthesized via the reaction of diallyl bisphenol A (DBPA) and 4‐nitrophthalonitrile. The chemical structure of DBPA‐Ph was confirmed by 1HNMR, 13CNMR, and FTIR spectroscopy. The curing behaviors and processability of DBPA‐Ph were studied by differential scanning calorimetry (DSC) and dynamic rheological analysis. The monomer manifested a two‐stage thermal polymerization pattern. The first stage was attributed to the polymerization of allyl groups and the second to the ring‐form polymerization of cyano groups. The result of dynamic rheological analysis indicated the monomer had wide curing window and the self‐catalyzed curing behavior. DBPA‐Ph polymers were prepared from the thermal polymerization with short curing time, showing high glass transition temperature (>350°C) and attractive thermal decomposition temperature (>430°C). The outstanding glass transition temperature, desirable thermo‐oxidative stabilities, good processability and sound process conditions could provide more applications to the DBPA‐Ph polymers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41203.
THE PARASITOID, Cotesia flavipes (CAMERON) (HYMENOPTERA: BRACONIDAE), INFLUENCES FOOD CONSUMPTION AND UTILIZATION BY LARVAL Diatraea saccharalis (F.) (LEPIDOPTERA: CRAMBIDAE)
Authors: Rossi Guilherme Duarte , Salvador Gabriela , Cônsoli Fernando Luis
Published: July 2014

Parasitoids exploit host insects for food and other resources; they alter host development and physiology to optimize conditions to favor parasitoid development. Parasitoids influence their hosts by injecting eggs, along with a variety of substances, including venoms, polydnaviruses, ovarian fluids, and other maternal factors, into hosts. These factors induce profound changes in hosts, such as behavior, metabolism, endocrine events, and immune defense. Because endoparasitoids develop and consume tissues from within their hosts, it is reasonable to suggest that internal parasitization would also influence host food consumption and metabolism. We report on the effects of parasitism by Cotesia flavipes on the food consumption and utilization of its host, Diatraea saccharalis. Cotesia flavipes reduces the host food consumption, but parasitized larvae considered a unit with their parasitoid's attained the same final weight as the nonparasitized larvae. Nutritional indices, midgut activities of carbohydrases, and trypsin of parasitized and nonparasitized D. saccharalis were assessed. Parasitized larvae had reduced relative food consumption, metabolic and growth rates, coupled with higher efficiency for conversion of the digested, but not ingested, food into body mass. Parasitism also affected food flux through the gut and protein contents in the midgut of parasitized larvae. The activity of α‐amylase and trehalase in parasitized host was enhanced in the first day after parasitism relative to control larvae. Saccharase activity remained unchanged during larval development. Trypsin activity was reduced from the fifth to ninth day after parasitism. We argue on the mechanisms involved in host food processing after parasitism.
Construction of Pendant‐Armed Schiff‐Base Macrocyclic Dinuclear Zinc Complexes and Their Selective Recognition of Acetate Ions
Authors: Zhang Kun , Jin Chao , Chen Hui‐Qing , Yin Gui , Huang Wei
Published: July 2014

Two new flexible extended dialdehydes (H2hpdd and H2pdd) with different functional pendant arms (CH2CH2PhOH and CH2CH2Ph) have been synthesized and reacted with 1,2‐bis(2‐aminoethoxy)ethane to prepare Schiff‐base macrocyclic complexes in the presence of a ZnII‐ion template. As a result, two preorganized dinuclear ZnII intermediates (1 and 2), as well as two 42‐membered folded [2+2] macrocyclic dinuclear ZnII complexes (3 and 4), were produced. The central zinc ions in compounds 1–4 showed distinguishable coordination patterns with the dialdehydes and the [2+2] macrocyclic ligands, in which a subtle pH‐adjustment function of the two pendant arms (with or without the phenolic hydroxy group) was believed to play a vital role. Furthermore, cation‐ and anion‐recognition experiments for complexes 3 and 4 revealed that they could selectively recognize acetate ions by the formation of 1:1 stoichiometric complexes, as verified by changes in their UV/Vis and MS (ESI) spectra and even by the naked eye.
High‐yield production of apoplast‐directed human adenosine deaminase in transgenic tobacco BY‐2 cell suspensions
Authors: Singhabahu Sanjeewa , George John , Bringloe David
Published: July 2014

Adenosine deaminase (ADA) deficiency, where a deleterious mutation in the ADA gene of patients results in a dysfunctional immune system, is ultimately caused by an absence of ADA. Over the last 25 years the disease has been treated with PEG‐ADA, made from purified bovine ADA coupled with polyethylene glycol (PEG). However, it is thought that an enzyme replacement therapy protocol based on recombinant human ADA would probably be a more effective treatment. With this end in mind, a human ADA cDNA was inserted into plant expression vectors used to transform tobacco plant cell suspensions. Transgenic calli expressing constructs containing apoplast‐directing signals showed significantly higher levels of recombinant ADA expression than calli transformed with cytosolic constructs. The most significant ADA activities, however, were measured in the media of transgenic cell suspensions prepared from high expressing transformed calli: where incorporation of a signal for arabinogalactan addition to ADA led to a recombinant protein yield of approximately 16 mg L−1, a 336‐fold increase over ADA produced by cell suspensions transformed with a cytosolic construct.
Implications of silica on biorefineries – interactions with organic material and mineral elements in grasses
Authors: Le Duy M. , Sørensen Hanne R. , Knudsen Niels Ole , Meyer Anne S.
Published: July 2014

Biorefineries aim to convert low value biomasses into high value products. The feedstock biomasses are often high‐silica agricultural waste products such as rice straw, wheat straw, corn stover, sugarcane bagasse, or empty fruit bunches. This causes challenges, since silica is problematic in industrial processes, where it forms water‐insoluble precipitates that are hard to remove, block filtration systems, and cause instrumental defects.

In this paper we review various industries that experience issues with silica. These include paper pulping and waste‐water treatment, where they try to solve their problems with silica in different ways. High pH and co‐precipitation with mineral elements are some common ways of alleviating silica problems. Reviewing the literature for the fundamentals of silica revealed a complex chemistry that is not yet fully understood. Much is still to be learned about the interactions between silica and organic material as well as the mechanisms of silica precipitation and dissolution. Understanding the fundamental and complex chemistry of silica might help developing better solutions than those existing today, allowing efficient use of high silica biomasses in biorefineries. © 2014 Society of Chemical Industry and John Wiley & Sons, Ltd
Optimal experimental designs for accelerated failure time with Type I and random censoring
Authors: Rivas‐López María J. , López‐Fidalgo Jesús , Campo Rodrigo del
Published: July 2014

Proportional Hazards models have been widely used to analyze survival data. In many cases survival data do not verify the assumption of proportional hazards. An alternative to the PH models with more relaxed conditions are Accelerated Failure Time models. These models are fairly commonly used in the field of manufacturing, but they are more and more frequent for modeling clinical trial data. They focus on the direct effect of the explanatory variables on the survival function allowing an easier interpretation of the effect of the corresponding covariates on the survival time. Optimal experimental designs are computed in this framework for Type I and random arrival. The results are applied to clinical models used to prevent tuberculosis in Ugandan adults infected with HIV.
A rhodamine‐based fluorescent probe for Cu(II) determination in aqueous solution
Authors: Mao Jie , Cheng Junhua , Wang Xuchun , Wang Shui , Cheng Nianshou , Wang Junfeng
Published: July 2014

An ‘off–on’ rhodamine‐based fluorescence probe for the selective detection of Cu(II) has been designed, exploiting the guest‐induced structure transform mechanism. This system shows a sharp Cu(II)‐selective fluorescence enhancement response in an aqueous system under physiological pH, and possesses high selectivity against a background of environmentally and biologically relevant metal ions. Under optimum conditions, the fluorescence intensity enhancement of this system is linearly proportional to the Cu(II) concentration from 50 nM to 6.0 μM with a detection limit of 29 nM. Copyright © 2014 John Wiley & Sons, Ltd.
Long-term outcome after parathyroidectomy for lithium-induced hyperparathyroidism
Authors: Norlén O , Sidhu S , Sywak M , Delbridge L
Published: July 2014

Background

The accepted management of lithium-associated hyperparathyroidism (LiHPT) is open four-gland parathyroid exploration (OPTX). This approach has recently been the subject of controversy. A recent study has shown very high long-term recurrence rates after OPTX, whereas some have promoted unilateral focused parathyroidectomy as appropriate management. The aim was to evaluate long-term outcomes after surgery for LiHPT and to assess the accuracy of preoperative imaging.

Methods

This was a retrospective cohort study that comprised all patients undergoing initial surgery for LiHPT between 1990 and 2013. The cumulative recurrence rate was calculated by the Kaplan–Meier method. The sensitivity and specificity of sestamibi scintigraphy and ultrasound imaging for identification of single-gland versus multigland disease was investigated using intraoperative assessment as reference.

Results

Of 48 patients, 45 had OPTX and three underwent focused parathyroidectomy. Multiglandular disease was documented in 27 patients and 21 had a single adenoma. The median follow-up was 5·9 (range 0·3–22) years and 16 patients died during follow-up. The 10-year cumulative recurrence rate was 16 (95 per cent confidence interval 2 to 29) per cent. No permanent complications occurred after primary surgery for LiHPT. Twenty-four patients had at least one preoperative ultrasound or sestamibi scan. For concordant sestamibi scintigraphy and ultrasound imaging, the sensitivity and specificity for identifying single-gland versus multigland disease was five of nine and five of eight respectively.

Conclusion

Surgery provided a safe and effective management option for patients with LiHPT in this series, with a long-term cure rate of well over 80 per cent.
Evaluation of a novel methacrylate‐based protein a resin for the purification of immunoglobulins and Fc‐fusion proteins
Authors: McCaw Tyler R. , Koepf Edward K. , Conley Lynn
Published: July 2014

Protein A affinity chromatography is a central part of most commercial monoclonal antibody and Fc‐fusion protein purification processes. In the last couple years an increasing number of new Protein A technologies have emerged. One of these new Protein A technologies consists of a novel, alkaline‐tolerant, Protein A ligand coupled to a macroporous polymethacrylate base matrix that has been optimized for immunoglobulin (Ig) G capture. The resin is interesting from a technology perspective because the particle size and pore distribution of the base beads are reported to have been optimized for high IgG binding and fast mass transfer, while the Protein A ligand has been engineered for enhanced alkaline tolerance. This resin was subjected to a number of technical studies including evaluating dynamic and static binding capacities, alkaline stability, Protein A leachate propensity, impurity clearance, and pressure–flow behavior. The results demonstrated similar static binding capacities as those achieved with industry standard agarose Protein A resins, but marginally lower dynamic binding capacities. Removal of impurities from the process stream, particularly host cell proteins, was molecule dependent, but in most instances matched the performance of the agarose resins. This resin was stable in 0.1 M NaOH for at least 100 h with little loss in binding capacity, with Protein A ligand leakage levels comparable to values for the agarose resins. Pressure–flow experiments in lab‐scale chromatography columns demonstrated minimal resin compression at typical manufacturing flow rates. Prediction of resin compression in manufacturing scale columns did not suggest any pressure limitations upon scale up. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1125–1136, 2014
Seven New Sesquiterpenoids from the Fruits of Schisandra sphenanthera
Authors: Tsai Yao‐Ching , Cheng Yuan‐Bin , Lo I‐Wen , Cheng Ho‐Hsi , Lin Ching‐Jie , Hwang Tsong‐Long , Kuo Yuh‐Chi , Liou Shorong‐Shii , Huang Yi‐Zsau , Kuo Yao‐Haur , Shen Ya‐Ching
Published: July 2014

Fractionation of the EtOH extract from the fruits of Schisandra sphenanthera resulted in the isolation of seven new sesquiterpenoids, 1–7, in addition to the known metabolites 8–23. Among them, schiscupatetralin A (1) possesses an unprecedented structure with a CC bond between cuparenol and tetralin. The isolated new compounds were evaluated for their anti‐HSV‐1 and anti‐inflammatory activities. The results revealed that compound 4 exhibited anti‐HSV‐1 activity, while compound 6 showed a significant anti‐inflammatory activity.
Electrophysiology Investigation of Trichogin GA IV Activity in Planar Lipid Membranes Reveals Ion Channels of Well‐Defined Size
Authors: Iftemi Sorana , De Zotti Marta , Formaggio Fernando , Toniolo Claudio , Stella Lorenzo , Luchian Tudor
Published: July 2014

Trichogin GA IV, an antimicrobial peptaibol, exerts its function by augmenting membrane permeability, but the molecular aspects of its pore‐forming mechanism are still debated. Several lines of evidence indicate a ‘barrel‐stave’ channel structure, similar to that of alamethicin, but the length of a trichogin helix is too short to span a normal bilayer. Herein, we present electrophysiology measurements in planar bilayers, showing that trichogin does form channels of a well‐defined size (R=4.2⋅109 Ω; corresponding at least to a trimeric aggregate) that span the membrane and allow ion diffusion, but do not exhibit voltage‐dependent rectification, unlike those of alamethicin.
Halogenated Metabolites Isolated from Penicillium citreonigrum
Authors: Yuan Wei‐Hua , Wei Zhi‐Wen , Dai Peng , Wu Hui , Zhao Yan‐Xia , Zhang Mei‐Mei , Jiang Nan , Zheng Wei‐Fa
Published: July 2014

Three chromone analogs, 1–3, a chlorinated alkaloid sclerotioramine (4), together with two 11‐noreremophilane‐type sesquiterpenes with a conjugated enolic OH group and a brominated one, 5 and 6, respectively, were isolated from Penicillium citreonigrum (HQ738282). Compounds 1, 5, and 6 were new. Biological tests revealed that 4 exhibited a significant activity (IC50 7.32 μg/ml), and 6 showed a moderate activity (IC50 16.31 μg/ml) in vitro against HepG2 cell line, and 4 also displayed an activity comparable to that of acarbose against α‐glucosidase.
New Isocoumarins from a Cold‐Adapted Fungal Strain Mucor sp. and Their Developmental Toxicity to Zebrafish Embryos
Authors: Feng Chun‐Chi , Chen Guo‐Dong , Zhao Yan‐Qiu , Xin Sheng‐Chang , Li Song , Tang Jin‐Shan , Li Xiao‐Xia , Hu Dan , Liu Xing‐Zhong , Gao Hao
Published: July 2014

Three new isocoumarin derivatives, mucorisocoumarins A–C (1–3, resp.), together with seven known compounds, 4–10, were isolated from the cold‐adapted fungal strain Mucor sp. (No. XJ07027‐5). The structures of the new compounds were identified by detailed IR, MS, and 1D‐ and 2D‐NMR analyses. It was noteworthy that compounds 1, 2, 4, and 5 were successfully resolved by chiral HPLC, indicating that 1–7 should exist as enantiomers. In an embryonic developmental toxicity assay using a zebrafish model, compound 3 produced developmental abnormalities in the zebrafish embryos. This is the first report of isocoumarins with developmental toxicity to zebrafish embryos.
Three New and Other Limonoids from the Hexane Extract of Melia azedarach Fruits and Their Cytotoxic Activities
Authors: Pan Xin , Matsumoto Masahiro , Nakamura Yasuhiro , Kikuchi Takashi , Zhang Jie , Ukiya Motohiko , Suzuki Takashi , Koike Kazuo , Akihisa Rima , Akihisa Toshihiro
Published: July 2014

A defatted fraction obtained from the hexane extract of the fruits of Melia azedarach L. (chinaberry tree; Meliaceae) exhibited cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines with IC50 values in the range of 2.9–21.9 μg/ml. Three new limonoids, 3‐deacetyl‐4′‐demethylsalannin (5), 3‐deacetyl‐28‐oxosalannin (14), and 1‐detigloylohchinolal (17), along with 16 known limonoids, 1–4, 6–13, 15, 16, 18, and 19, and one known triterpenoid, 20, were isolated from the fraction. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. These compounds were evaluated for their cytotoxic activities against the four cancer cell lines mentioned above. 3‐Deacetyl‐4′‐demethyl‐28‐oxosalannin (16), which exhibited potent cytotoxicity against AZ521 (IC50 3.2 μM) cells, induced typical apoptotic cell death in AZ521 cells upon evaluation of the apoptosis‐inducing activity by flow cytometry. This work provided, furthermore, valuable information on the structural features of limonoids of the fruits and/or seeds of Melia azedarach and related Meliaceae plants, M. toosendan and Azadirachta indica.
Expression of ganglioside 9‐O acetyl GD3 in undifferentiated embryonic stem cells
Authors: Azevedo‐Pereira Ricardo Luiz , Morrot Alexandre , Machado Gabriele Santos , Paredes Bruno Diaz , de Carvalho Rodrigues Deivid , de Carvalho Antonio Carlos Campos , Mendez‐Otero Rosalia
Published: July 2014

Embryonic stem cells (ES cells) express a transient and heterogeneous pattern of molecules, which suggests a notable mechanism to control self‐renewal avoid the differentiation into germ layers. We show that 9‐O‐acetyl GD3 (9OacGD3), a highly expressed b‐series ganglioside in neural stem (NS) cells, is expressed in undifferentiated mouse ES cells in a heterogeneous fashion. After sorting, undifferentiated 9OacGD3+ES cell population had higher levels of nestin and Sox2 mRNA than the 9OacGD3−cells. Even with elevated expression of these neural transcription factors, 9OacGD3+cells did not give rise to more neural progenitors than 9OacGD3−cells. Expression of 9OacGD3 was recovered from 9OacGD3−cell population, demonstrating that expression of this ganglioside in mouse embryonic stem cells is transient, and does not reflect cell fate. Our findings show that the ganglioside 9OacGD3 is expressed heterogeneously and transiently in ES cells, and this expression corresponds to higher levels of Sox2 and Nestin transcripts.
Leptin induces ADAMTS‐4, ADAMTS‐5, and ADAMTS‐9 genes expression by mitogen‐activated protein kinases and NF‐ĸB signaling pathways in human chondrocytes
Authors: Yaykasli Kursat Oguz , Hatipoglu Omer Faruk , Yaykasli Emine , Yildirim Kubra , Kaya Ertugrul , Ozsahin Mustafa , Uslu Mustafa , Gunduz Esra
Published: July 2014

Elucidation of the causes of inflammation has vital importance in the development of new approaches for the treatment of arthritic diseases. The degradation of aggrecan by upregulated disintegrin and metalloproteinase with trombospondin motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis (RA) and osteoarthritis (OA). Increased levels of leptin in both RA and OA have been demonstrated, thus linking leptin to arthritic diseases, but the mechanism has not been clarified. This study investigated the putative role of signaling pathways (p38, JNK, MEK1, NF‐ĸB, and PI3) involved in leptin‐induced cartilage destruction. Normal human articular chondrocytes were cultured with recombinant human leptin at 100, 250, 500, and 1000 ng/mL doses for 6, 12, 24, and 48 h, after which ADAMTS‐4, ‐5, and ‐9 genes expression were determined by real time‐polymerase chain reaction (RT‐PCR) and Western Blot methods. The signaling pathways involved in leptin‐induced ADAMTSs upregulation were also investigated by using inhibitors of signaling pathways. It was demonstrated that ADAMTSs expression level was peaked at 1000 ng/mL doses for 48 hours, and MAPKs (p38, JNK, and MEK) and NF‐ĸB signaling pathways involving in leptin triggered ADAMTSs upregulation. Obesity as a risk for RA and OA may contribute to the inflammation of both RA and OA diseases by secreting adipokines like leptin. We hypothesize that leptin is involved in the development of RA and OA accompanied with obesity by increasing ADAMTS‐4, ‐5, and ‐9 genes expression via MAPKs and NF‐ĸB signaling pathways.
Induced Chirality in a Metal–Organic Framework by Postsynthetic Modification for Highly Selective Asymmetric Aldol Reactions
Authors: Demuynck Anneleen L. W. , Goesten Maarten G. , Ramos‐Fernandez Enrique V. , Dusselier Michiel , Vanderleyden Jozef , Kapteijn Freek , Gascon Jorge , Sels Bert F.
Published: July 2014

A straightforward synthetic route to chiral metal–organic frameworks is proposed that relies on an acid–base interaction between an acid linker and a chiral primary amino acid derived diamine organocatalyst. High ee values for the aldol condensation of linear ketones and aromatic aldehydes are reported with this heterogeneous catalyst. Three consecutive catalyst reuse experiments demonstrated that the majority of the activity was preserved, as was the enantioselectivity.
Selective Conversion of Cellulose to Hydroxymethylfurfural in Polar Aprotic Solvents
Authors: Weingarten Ronen , Rodriguez‐Beuerman Alexandra , Cao Fei , Luterbacher Jeremy S. , Alonso David Martin , Dumesic James A. , Huber George W.
Published: July 2014

Herein, we report a new reaction pathway to produce hydroxymethylfurfural (HMF) from cellulose under mild reaction conditions (140–190 °C; 5 mM H2SO4) in polar aprotic solvents (i.e. THF) without the presence of water. In this system, levoglucosan is the major decomposition product of cellulose, followed by dehydration to produce HMF. Glucose, levulinic acid, and formic acid are also produced as a result of side reactions with water, which is a by‐product of dehydration. The turnover frequency for cellulose conversion increases as the water content in the solvent decreases, with conversion rates in THF being more than twenty times higher than those in water. The highest HMF yield from cellulose was 44 % and the highest combined yield of HMF and levulinic from cellulose was 53 %, which are nearly comparable to yields obtained in ionic liquids or biphasic systems. Moreover, the use of a low boiling point solvent, such as THF, facilitates recovery of HMF in downstream processes.
Highly Efficient Chiral Resolution of dl‐Arginine by Cocrystal Formation Followed by Recrystallization under Preferential‐Enrichment Conditions
Authors: Iwama Sekai , Kuyama Kazunori , Mori Yuko , Manoj Kochunnoonny , Gonnade Rajesh G. , Suzuki Katsuaki , Hughes Colan E. , Williams P. Andrew , Harris Kenneth D. M. , Veesler Stéphane , Takahashi Hiroki , Tsue Hirohito , Tamura Rui
Published: July 2014

An excellent chiral symmetry‐breaking spontaneous enantiomeric resolution phenomenon, denoted preferential enrichment, was observed on recrystallization of the 1:1 cocrystal of dl‐arginine and fumaric acid, which is classified as a racemic compound crystal with a high eutectic ee value (>95 %), under non‐equilibrium crystallization conditions. On the basis of temperature‐controlled video microscopy and in situ time‐resolved solid‐state 13C NMR spectroscopic studies on the crystallization process, a new mechanism of phase transition that can induce preferential enrichment is proposed.
Enhanced Hydrolytic Stability of Siliceous Surfaces Modified with Pendant Dipodal Silanes
Authors: Arkles Barry , Pan Youlin , Larson Gerald L. , Singh Mani
Published: July 2014

Dipodal silanes possess two silicon atoms that can covalently bond to a surface. They offer a distinct advantage over conventional silanes commonly used for surface modification in terms of maintaining the integrity of surface coatings, adhesive primers, and composites in aqueous environments. New nonfunctional and functional dipodal silanes with structures containing “pendant” rather than “bridged” organofunctionality are introduced. The stability of surfaces in aqueous environments prepared from dipodal silanes with hydrophobic alkyl functionality is compared to the stability of similar surfaces prepared from the conventional silanes. In strongly acidic and brine environments, surfaces modified with dipodal silanes demonstrate markedly improved resistance to hydrolysis compared to surfaces prepared from conventional silanes. Pendant dipodal silanes exhibit greater stability than bridged dipodal silanes. The apparent equilibrium constant for the formation of silanol species by the hydrolysis of a disiloxane bond was determined as Kc=[SiOH]2/[Si‐O‐Si][H2O]=6±1×10−5 and is helpful in understanding the enhanced hydrolytic stability of surfaces modified with dipodal silanes.
Luminescent Hybrid Materials Based on Laponite Clay
Authors: Li Huanrong , Li Man , Wang Yu , Zhang Wenjun
Published: July 2014

The spectroscopic behavior of ionic Eu3+ or Tb3+ complexes of an aromatic carboxyl‐functionalized organic salt as well as those of the hybrid materials derived from adsorption of the ionic complexes on Laponite clay are reported. X‐ray diffraction (XRD) patterns suggest that the complexes are mainly adsorbed on the outer surfaces of the Laponite disks rather than intercalated within the interlayer spaces. Photophysical data showed that the energy‐transfer efficiency from the ligand to Eu3+ ions in the hybrid material is increased remarkably with respect to the corresponding ionic complex. The hybrid material containing the Eu3+ complex shows bright red emission from the prominent 5D0→7F2 transition of Eu3+ ions, and that containing the Tb3+ complex exhibits bright green emission due to the dominant 5D4→7F5 transition of Tb3+ ions.
Water Compatible Photoarylation of Amino Acids and Peptides
Authors: Sudakow Alex , Papke Uli , Lindel Thomas
Published: July 2014

A novel photoarylation of amino acids and peptides is described, which tolerates the presence of water. Irradiation of Boc‐protected amino acids in the presence of N‐protected 2‐azidobenzimidazoles leads to selective arylation of carboxy termini or side chains. The new reaction also works for peptides. Irradiation of the nonapeptide H‐SPSYVYHQF‐OH also resulted in selective arylation of the tyrosine side chains, as indicated by ESI‐MS/MS fragmentation. Chemo‐ and regioselectivity could add the title reaction to the repertoire of photoaffinity labeling methods.
Stereoselective Hydrodehalogenation via a Radical‐Based Mechanism Involving T‐Shaped Chiral Nickel(I) Pincer Complexes
Authors: Rettenmeier Christoph , Wadepohl Hubert , Gade Lutz H.
Published: July 2014

We herein report the catalytic enantioselective hydrodehalogenation based on the interplay of a chiral molecular nickel(I)/nickel(II)hydride system. Prochiral geminal dihalogenides are dehalogenated via a secondary configurationally unstable, potentially metal‐stabilized radical intermediate. In a subsequent step, the liberated radical is then trapped by the nickel(II) hydrido complex, present in a large excess under the catalytic conditions, which in turn induces the enantioselectivity during the hydrogen atom transfer onto the radical intermediate. These new chiral nickel(I) complexes were found to catalyze the asymmetric hydrodehalogenation of geminal dihalogenides with moderate to good enantiomeric excess values using LiEt3BH as reductant. The main side product generally observed is the dehalogenated alkene, whereas the hydrodehalogenation of the chiral monohalogen compound occurred much more slowly despite the large excess of reductant.
Electronic Transitions in Conformationally Controlled Tetrasilanes with a Wide Range of SiSiSiSi Dihedral Angles
Authors: Tsuji Hayato , Fogarty Heather A. , Ehara Masahiro , Fukuda Ryoichi , Casher Deborah L. , Tamao Kohei , Nakatsuji Hiroshi , Michl Josef
Published: July 2014

Unlike π‐electron chromophores, the peralkylated n‐tetrasilane σ‐electron chromophore resembles a chameleon in that its electronic spectrum changes dramatically as its silicon backbone is twisted almost effortlessly from the syn to the anti conformation (changing the SiSiSiSi dihedral angle ω from 0 to 180°). A combination of UV absorption, magnetic circular dichroism (MCD), and linear dichroism (LD) spectroscopy on conformationally controlled tetrasilanes 1–9, which cover fairly evenly the full range of angles ω, permitted a construction of an experimental correlation diagram for three to four lowest valence electronic states. The free chain tetrasilane n‐Si4Me10 (10), normally present as a mixture of three enantiomeric conformer pairs of widely different angles ω, has also been included in our study. The spectral trends are interpreted in terms of avoided crossings of 1B with 2B and 2A with 3A states, in agreement with SAC‐CI calculations on the excited states of 1–7 and conformers of 10.
Small Cycloalkane (CN)2CC(CN)2 Structures Are Highly Directional Non‐covalent Carbon‐Bond Donors
Authors: Bauzá Antonio , Mooibroek Tiddo J. , Frontera Antonio
Published: July 2014

High‐level calculations (RI‐MP2/def2‐TZVP) disclosed that the σ‐hole in between two C atoms of cycloalkane X2CCX2 structures (X=F, CN) is increasingly exposed with decreasing ring size. The interacting energy of complexes of F−, HO−, N≡C−, and H2CO with cyclopropane and cyclobutane X2CCX2 derivatives was calculated. For X=F, these energies are small to positive, while for X=CN they are all negative, ranging from −6.8 to −42.3 kcal mol−1. These finding are corroborated by a thorough statistical survey of the Cambridge Structural Database (CSD). No clear evidence could be found in support of non‐covalent carbon bonding between electron‐rich atoms (El.R.) and F2CCF2 structures. In marked contrast, El.R.⋅⋅⋅(CN)2CC(CN)2 interactions are abundant and highly directional. Based on these findings, the hydrophobic electrophilic bowl formed by 1,1′,2,2′‐tetracyano cyclopropane or cyclobutane derivatives is proposed as a new and synthetically accessible supramolecular synthon.
Influences of Land Use/Land Cover on Hydrogeochemical Indexes of Karst Groundwater in the Dagouhe Basin, Southwest China
Authors: Lan Funing , Qin Xiaoqun , Jiang Zhongcheng , Meng Rongguo , Mo Risheng , Yang Shengmeng , Wang Wenjuan , An Shuqing
Published: July 2014

It is essential to understand how karst groundwater hydrogeochemistry responds to watershed land use and land cover changes. However, little information is available on this response in the karst region of southwest China. Water temperature, pH, electrical conductivity, total organic carbon (TOC), ions concentration, CO2 pressure (pCO2), calcite saturation index (SIC), stable carbon isotopic compositions of dissolved inorganic carbon (δ13CDIC), and carbon sink ability were monitored during the hydrological year of May 2010 to April 2011 in the eastern and western areas of Dagouhe Basin. The two areas share the same climatic condition but show different land use/land cover. Field data were used to calculate pCO2, SIC, and karst carbon sink density. The results showed higher ion concentrations, TOC, carbon sink ability, pCO2 and lower pH, SIC, δ13C in the groundwater of the eastern area than those in the western area. In the eastern area, there is larger forest and farmland coverage, both produced and kept more biological carbon sources and lower δ13C in the soil‐vadose zone. While in the western area, there is larger rocky land and wasteland coverage. All results suggested that land use and land cover pattern played very important roles in this basin. Therefore, the hydrogeochemical indexes selected could be good indicators for the land use/cover change in the studied basin.
6‐Hydroxybenzothiophene Ketones: Potent Inhibitors of 17β‐Hydroxysteroid Dehydrogenase Type 1 (17β‐HSD1) Owing to Favorable Molecule Geometry and Conformational Preorganization
Authors: Miralinaghi Parisa , Schmitt Christian , Hartmann Rolf W. , Frotscher Martin , Engel Matthias
Published: July 2014

The inhibition of 17β‐hydroxysteroid dehydrogenase type 1 (17β‐HSD1), which catalyzes the conversion of estrone into the potent estrogen receptor agonist estradiol (E2), is discussed as a novel therapeutic approach for the treatment of estrogen‐dependent diseases. Because the reduction of E2 would be basically limited to the target tissues, this approach is expected to cause fewer side effects than the currently employed antihormonal therapies. Recently, we reported on 6‐hydroxybenzothiazole ketones as a new class of 17β‐HSD1 inhibitors with a notable activity/selectivity profile. In an attempt to further optimize these parameters, we modified the benzothiazole core by a systematic bioisosteric replacement. Thus, we were able to identify a new 6‐hydroxybenzothiophene derivative that displayed stronger inhibition of 17β‐HSD1 (IC50=13 nM) and that was also more selective than a benzothiazole analog. Using ab initio calculations, we found that the higher potency of the 6‐hydroxybenzothiophene derivative was probably due to more favorable conformational preorganization of the scaffold for binding to the enzyme.
Design of a General‐Purpose European Compound Screening Library for EU‐OPENSCREEN
Authors: Horvath Dragos , Lisurek Michael , Rupp Bernd , Kühne Ronald , Specker Edgar , von Kries Jens , Rognan Didier , Andersson C. David , Almqvist Fredrik , Elofsson Mikael , Enqvist Per‐Anders , Gustavsson Anna‐Lena , Remez Nikita , Mestres Jordi , Marcou Gilles , Varnek Alexander , Hibert Marcel , Quintana Jordi , Frank Ronald
Published: July 2014

This work describes a collaborative effort to define and apply a protocol for the rational selection of a general‐purpose screening library, to be used by the screening platforms affiliated with the EU‐OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening‐compliant physicochemical properties, loose compliance to drug‐likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre‐filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in‐house methodology and expertise. An in‐depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics‐driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general‐purpose self‐organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU‐OPENSCREEN library could be directly compared with distributions of known bioactives of various classes. This mapping highlights the relevance of the selection and shows how the consensus reached by merging the five different 40K selections contributes to achieve this relevance. The approach also allows one to readily identify subsets of target‐ or target‐class‐oriented compounds from the EU‐OPENSCREEN library to suit the needs of the diverse range of potential users. The final EU‐OPENSCREEN library, assembled by merging five independent selections of 40K compounds from various expert groups, represents an excellent example of a Europe‐wide collaborative effort toward the common objective of building best‐in‐class European open screening platforms.
Lung cancer adrenal gland metastasis: Optimal fine‐needle aspirate and touch preparation smear cellularity characteristics for successful theranostic next‐generation sequencing
Authors: Gleeson Ferga C. , Kipp Benjamin R. , Levy Michael J. , Voss Jesse S. , Campion Michael B. , Minot Douglas M. , Tu Zheng J. , Klee Eric W. , Lazaridis Konstantinos N. , Kerr Sarah E.
Published: July 2014

BACKGROUND

Multigene molecular testing to guide personalized therapy for oncology patients is of increasing clinical relevance. Molecular testing of fine‐needle aspiration samples is underused, but when acquired with minimally invasive techniques could become the standard of care to obtain theranostic specimens. The aims of the current study were to identify key cytology specimen selection criteria suitable for next‐generation sequencing (NGS) and to determine the prevalence and spectrum of pathogenic alterations in a cohort of patients with AJCC stage IV lung cancer.

METHODS

A total of 70 adrenal gland cytology specimens with direct smears were screened to identify 56 patients with a single slide containing at least 300 total cells and 20% tumor nuclei. After DNA extraction, the NGS protocols were used to simultaneously detect mutations in >2800 exonic regions in 50 key cancer genes.

RESULTS

A total of 28 specimens produced acceptable NGS results. Specimens with a combined critical cell mass (>5000 viable cells) and a DNA concentration >5 ng/µL resulted in a 95% chance of successful sequencing. A total of 37 pathogenic alterations were identified in 10 genes and in 25 patients (85%). A pathogenic alteration (≥1) linked to available or developing targeted therapies was revealed in 50% of cases.

CONCLUSIONS

The data from the current study demonstrate that theranostic NGS can be applied to adrenal gland metastasis using routine cytologic smear specimens. The characteristics of such smears could be evaluated during onsite adequacy assessment by cytopathology professionals. This model greatly augments the opportunity for customized genotype‐directed therapy from minimally invasive techniques. Cancer (Cancer Cytopathol) 2014;122:822–832. © 2014 American Cancer Society.