bluuebunny/crossref_metadata_2025 huggingface dataset:
O simpósio “A educação que nos convém: o IPES e a ação político-ideológica da burguesia na década de 1960”
Authors: Carvalho Celso Do Prado Ferraz de
Published: May 2011

Este artigo tem como finalidade apresentar resultados de uma pesquisa sobre a relação universidade – empresa, com base no itinerário percorrido por uma instituição orgânica da burguesia, fundada em 1961: o Instituto de Pesquisas e Estudos Sociais (IPES). Este estudo busca mostrar o instituto como parte de um movimento maior da burguesia que influencia na definição das políticas públicas para transformar a universidade em um espaço próximo aos interesses da indústria. A partir da perspectiva gramsciana de intelectual orgânico, a pesquisa possibilita que se analise tanto o discurso quanto a fala dos dirigentes do instituto, ao longo da década de 1960, e sua relação com as mudanças na atual conjuntura política do país.
Norbert Elias & a educação de Andréa Borges Leão
Authors: Soares Maria Lucia de Amorim
Published: May 2011

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Wear Performance of Dental Materials: A Comparison of Substructure Ceramics, Veneering Ceramics, and Non‐Precious Alloys
Authors: Preis Verena , Hahnel Sebastian , Kolbeck Carola , Behrend Detlef , Warkentin Mareike , Handel Gerhard , Rosentritt Martin
Published: May 2011

The aim of this in vitro study was to compare the two‐body wear resistance of different dental ceramics and non‐precious alloys. Two‐body wear tests were performed in a chewing simulator with steatite antagonists. A pin‐on‐block design with a vertical load of 50 N for 1.2 × 105 cycles (f = 1.6 Hz; lateral movement: 1 mm, mouth opening: 2 mm) was used for the wear test. Surface roughness Ra (SP6, Perthen‐Feinprüf, G) and wear depth were determined using a 3D‐Profilometer (Laserscan 3D, Willytec, G). Scanning electron microscopy (Quanta FEG 400, FEI, NL) was applied for evaluating wear performance of both, materials and antagonists. Statistics: one‐way ANOVA (α = 0.05). The in vitro wear test showed that the wear performance of dental materials is strongly influenced by the type of material (ceramic, zirconia, or alloy). Zirconia and alloy provided low wear in contrast to glass‐ceramic systems. In contradiction to common expectations, hard zirconia and alloy systems showed even lower antagonistic wear than glass‐ceramics.
Tailoring of LaxSr1‐xCoyFe1‐yO3‐δ Nanostructure by Pulsed Laser Deposition
Authors: Plonczak Pawel , Bieberle‐Hütter Anja , Søgaard Martin , Ryll Thomas , Martynczuk Julia , Hendriksen Peter Vang , Gauckler Ludwig J.
Published: May 2011

Pulsed Laser Deposition (PLD) was used to prepare thin films with the nominal composition La0.58Sr0.4Co0.2Fe0.8O3‐δ (LSCF). The thin film microstructure was investigated as a function of PLD deposition parameters such as: substrate temperature, ambient gas pressure, target‐to‐substrate distance, laser fluence and frequency. It was found that the ambient gas pressure and the substrate temperature are the key PLD process parameters determining the thin film micro‐ and nanostructure. A map of the LSCF film nanostructures is presented as a function of substrate temperature (25–700 °C) and oxygen background pressure (0.013–0.4 mbar), with film structures ranging from fully dense to highly porous. Fully crystalline, dense, and crack‐free LSCF films with a thickness of 300 nm were obtained at an oxygen pressure lower than 0.13 mbar at a temperature of 600 °C. The obtained knowledge on the structure allows for tailoring of perovskite thin film nanostructure, e.g., for solid oxide fuel cell cathodes. A simple geometrical model is proposed, allowing estimation of the catalytic active surface area of the prepared thin films. It is shown that voids at columnar grain boundaries can result in an increase of the surface area by approximately 25 times, when compared to dense flat films.
Streptavidin‐Functionalized Silver‐Nanoparticle‐Enriched Carbon Nanotube Tag for Ultrasensitive Multiplexed Detection of Tumor Markers
Authors: Lai Guosong , Wu Jie , Ju Huangxian , Yan Feng
Published: May 2011

A streptavidin‐functionalized silver‐nanoparticle‐enriched carbon nanotube (CNT/Ag NP) is designed as trace tag for ultrasensitive multiplexed measurements of tumor markers using a disposable immunosensor array. The CNT/Ag NP nanohybrid is prepared by one‐pot in situ deposition of Ag NPs on carboxylated CNTs. The nanohybrid is functionalized with streptavidin via the inherent interaction between the protein and Ag NPs for further linkage of biotinylated signal antibodies to obtain tagged antibodies. The functionalization process greatly improves the dispersibility of the nanohybrid in water. The immunosensor array is prepared by covalently immobilizing capture antibodies on chitosan‐modified screen‐printed carbon electrodes. Through a sandwich‐type immunoreaction on the immunosensor array, numerous Ag NPs are captured onto every single immunocomplex and are further amplified by a subsequent Ag NP‐promoted deposition of silver from a silver enhancer solution to obtain the sensitive electrochemical‐stripping signal of the Ag NPs. Using carcinoembryonic antigen and α‐fetoprotein as model analytes, this proposed multiplexed immunoassay method shows acceptable precision and wide linear ranges over four orders of magnitude with detection limits down to 0.093 and 0.061 pg mL−1, respectively. The assay results of serum samples with the proposed method are in acceptable agreement with the reference values. The newly designed strategy and the functionalized tag avoid cross‐talk and the requirement of deoxygenation for electrochemical immunoassay, and thus provide a promising potential in clinical application.
Effect of silanes on the morphology, hydrophobicity, and dynamical mechanical properties of polyimide/silica hybrid membranes
Authors: Chen Chiou‐Juy , Lu Hsu‐Tung , Tseng Wen‐Yen , Tseng I‐Hsiang , Huang Shih‐Liang , Tsai Mei‐Hui
Published: May 2011

Polyimide (PI)/silica hybrid membranes with high contact angles were prepared through the in situ sol–gel process. The precursor, poly(amic acid) with controlled block chain length, was synthesized using 4,4′‐diaminodiphenyl ether (ODA), 3,3′,4,4′‐benzophenone‐tetracarboxylic dianhydride (BTDA) and 3‐aminopropyl‐trimethoxysilane (APrTMOS) or 3‐aminopropyldimethylethoxysilane (APDiMOS). And then, phenyltrimethoxysilane (PTS) or tetramethoxysilane (TMOS) or methyltrimethoxysilane (MTrMOS) was respectively, added to the above polyamic acid and mixed thoroughly. Following curing reaction, the PI/silica hybrid membranes with different cross‐linkages, silica content, and hydrophobic properties were prepared. The effect on the formation of PI imide ring during imidization reaction is increased as the increase of silanes content and characterized by frequency shiftment and absorbance ratio of Fourier transform infrared (FTIR) measurements. All the hybrid membranes show high transparency though with high silica contents. The storage modulus, tan δ, and damping intensity by DMA measurements are all correlated with silane content or block chain length. And all these membranes with silane content possess high contact angle as compared to pure PI without any silanes added and the contact angles increase with increasing the silane content. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Investigations of thermal degradation behavior and fire performance of halogen‐free flame retardant poly(1,4‐butylene terephthalate) composites
Authors: Yang Wei , Song Lei , Hu Yuan , Lu Hongdian , Yuen Richard K.K.
Published: May 2011

This work aims to develop halogen‐free poly(1,4‐butylene terephthalate) (PBT) composites with enhanced flame retardancy using ecofriendly flame retardants, aluminum hypophosphite (AHP) and melamine derivatives (melamine polyphosphate and melamine cyanurate). Microscale combustion calorimetry and thermal gravimetric analysis/infrared spectrometry (TG‐IR) technique were used to investigate the potential fire hazards of these PBT composites. For the PBT composites with the incorporation of AHP and melamine derivatives, the heat release capacity (HRC) which is an indicator of a material fire hazard was significantly reduced, and the intensities of a variety of combustible or toxic gases detected by TG‐IR technique were remarkably decreased. Moreover, a loading of 20 wt % flame retardant mixture fulfilled the PBT composites high limited oxygen index (LOI) and V‐0 classification in UL 94 testing. An intumescent flame retarded mechanism was speculated in this work, because numerous bubble‐like char residues were found on the surface of the samples containing flame retardant mixture after LOI testing. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Thermosensitive properties of semi‐IPN gel composed of amphiphilic gel and thermosensitive polymer in buffer solution
Authors: Takahashi Atsushi , Sakohara Shuji
Published: May 2011

In this study, a semi‐interpenetrating polymer network (semi‐IPN) gel comprising a crosslinked amphiphilic N,N‐dimethylacrylamide‐co‐N‐isopropylacrylamide gel and interpenetrating thermosensitive poly(N‐isopropylacrylamide) (poly(NIPAM)) was prepared. Their thermosensitive behaviors in a buffer solution comprising sodium chloride, sodium citrate, and sodium dodecyl sulfate, which are generally used in biochips, were investigated. At low temperatures, the gel in the buffer solution was absolutely transparent. However, when the gel was heated, it became milky white or opaque without changes in the gel size. It is well known that the network or crosslink distribution of the transparent gel is homogeneous macroscopically, whereas that of the opaque gel is inhomogeneous; in other words, the network of the opaque gel consists of coarse and dense parts. The structural changes in the gel network were confirmed by the temperature dependence of the permeability of the buffer solution through the semi‐IPN gel membrane. The permeability increased stepwise when the gel became opaque due to heating. The structural changes in the semi‐IPN gel network depended on the compositions of the buffer solution and gel, i.e., the copolymerization ratio of NIPAM in the gel and the content of the poly(NIPAM) molecules in the gel. These results suggest that the thermosensitive behaviors of the semi‐IPN gel strongly depend on the interactions between the copolymerized NIPAM in the gel network and the poly(NIPAM) molecules. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Optimization of synthesis and characterization of cassava starch‐graft‐poly(acrylonitrile) using response surface methodology
Authors: Jyothi Alummoottil N. , Sajeev Moothandasery S. , Parvathy Prabha C. , Sreekumar Janardanan
Published: May 2011

Graft copolymerization of poly(acrylonitrile) onto cassava starch was carried out with potassium persulphate (PPS) as the free radical initiator using a response surface Box–Behnken design. Different levels of monomer concentration, initiator concentration, and temperature were used, and regression models were generated in terms of these factors, which can be used to predict the grafting level and efficiency at a given level of the factors. The grafted starches were characterized by FTIR, XRD, and SEM analyses and determination of %grafting (%G), N‐content, thermal properties, water and saline solution retention, and rheological properties. Under the conditions used, %G was found to depend only on the temperature used for the reaction. The maximum %G of 120.1 was obtained for the sample synthesized under the following conditions: weight of AN = 0.753 mol/10 g starch, weight of PPS = 0.284 g and temperature = 55°C, and the grafting efficiency was 30.03%. The absorption bands at 2243 cm−1 for the nitrile group (CN) in the FTIR spectra of the products confirmed the grafting reaction. There was a decrease in crystallinity and disappearance of the granular structure after grafting of the starch. The melting temperatures of the graft copolymers determined by differential scanning calorimetry analysis were higher than that of the native starch. The grafted starches exhibited very high thermal stability as observed from the thermogravimetric analysis. The superabsorbent polymer prepared from the grafted starch by alkali saponification exhibited a maximum water absorbency of 636 g/g. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Preparation and mechanical properties of high‐performance short ramie fiber‐reinforced polypropylene composites
Authors: Feng Yulin , Hu Yuexin , Zhao Guiyan , Yin Jinghua , Jiang Wei
Published: May 2011

Short ramie fiber (RF) was used to reinforce the polypropylene (PP). The composites were prepared in a twin‐screw extruder followed by injection molding. The experimental results showed that both the strength and the modulus of the composites increase considerably with increasing RF content. The tensile strength and flexural strength are as high as 67 and 80 MPa by the incorporation of ramie up to 30 wt %. To the best of our knowledge, this is one of the best results for short natural fiber‐reinforced PP composites. However, the preparation method in this study is more simple and economic. This short RF‐reinforced PP composites extend the application field for short‐nature fiber‐reinforced PP composites. Morphological analysis revealed that it is the high aspect ratio of the fiber and good interfacial compatibility that result in the high performance of the composites. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Novel assays of thrombogenic pathogenicity in the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen β2‐glycoprotein I
Authors: Ioannou Yiannis , Zhang Jing‐Yun , Qi Miao , Gao Lu , Qi Jian Cheng , Yu De‐Min , Lau Herman , Sturgess Allan D. , Vlachoyiannopoulos Panayiotis G. , Moutsopoulos Haralampos M. , Rahman Anisur , Pericleous Charis , Atsumi Tatsuya , Koike Takao , Heritier Stephane , Giannakopoulos Bill , Krilis Steven A.
Published: May 2011

Objective

Beta‐2‐glycoprotein I (β2GPI) constitutes the major autoantigen in the antiphospholipid syndrome (APS), a common acquired cause of arterial and venous thrombosis. We recently described the novel observation that β2GPI may exist in healthy individuals in a free thiol (biochemically reduced) form. The present study was undertaken to quantify the levels of total, reduced, and posttranslationally modified oxidized β2GPI in APS patients compared to various control groups.

Methods

In a retrospective multicenter analysis, the proportion of β2GPI with free thiols in serum from healthy volunteers was quantified. Assays for measurement of reduced as well as total circulating β2GPI were developed and tested in the following groups: APS (with thrombosis) (n = 139), autoimmune disease with or without persistent antiphospholipid antibodies (aPL) but without APS (n = 188), vascular thrombosis without APS or aPL (n = 38), and healthy volunteers (n = 91).

Results

Total β2GPI was significantly elevated in patients with APS (median 216.2 μg/ml [interquartile range 173.3–263.8]) as compared to healthy subjects (median 178.4 μg/ml [interquartile range 149.4–227.5] [P < 0.0002]) or control patients with autoimmune disease or vascular thrombosis (both P < 0.0001). The proportion of total β2GPI in an oxidized form (i.e., lacking free thiols) was significantly greater in the APS group than in each of the 3 control groups (all P < 0.0001).

Conclusion

This large retrospective multicenter study shows that posttranslational modification of β2GPI via thiol‐exchange reactions is a highly specific phenomenon in the setting of APS thrombosis. Quantification of posttranslational modifications of β2GPI in conjunction with standard laboratory tests for APS may offer the potential to more accurately predict the risk of occurrence of a thrombotic event in the setting of APS.
Folate‐targeted nanoparticles show efficacy in the treatment of inflammatory arthritis
Authors: Thomas Thommey P. , Goonewardena Sascha N. , Majoros Istvan J. , Kotlyar Alina , Cao Zhengyi , Leroueil Pascale R. , Baker James R.
Published: May 2011

Objective

To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 [G5]) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and to investigate the activity of an FA‐ and methotrexate (MTX)–conjugated dendrimer (G5‐FA‐MTX) as a therapeutic for the inflammatory disease of arthritis.

Methods

In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescence‐tagged G5‐FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen‐induced arthritis to evaluate the therapeutic potential of G5‐FA‐MTX.

Results

Folate‐targeted dendrimer bound and internalized in a receptor‐specific manner into both folate receptor β–expressing macrophage cell lines and primary mouse macrophages. The conjugate G5‐FA‐MTX acted as a potent antiinflammatory agent and reduced arthritis‐induced parameters of inflammation such as ankle swelling, paw volume, cartilage damage, bone resorption, and body weight decrease.

Conclusion

The use of folate‐targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.
Blockade of NKG2D ameliorates disease in mice with collagen‐induced arthritis: A potential pathogenic role in chronic inflammatory arthritis
Authors: Andersson Anna K. , Sumariwalla Percy F. , McCann Fiona E. , Amjadi Parisa , Chang Chiwen , McNamee Kay , Tornehave Ditte , Haase Claus , Agersø Henrik , Stennicke Vibeke W. , Ahern David , Ursø Birgitte , Trowsdale John , Feldmann Marc , Brennan Fionula M.
Published: May 2011

Objective

To assess the role of the activating receptor NKG2D in arthritis.

Methods

Levels of NKG2D and its ligands were determined by fluorescence‐activated cell sorting, real‐time polymerase chain reaction, and immunohistochemistry in rheumatoid arthritis (RA) synovial membrane tissue and in paw tissue from arthritic mice. Arthritis was induced in DBA/1 mice by immunization with type II collagen, and mice were treated intraperitoneally with a blocking anti‐NKG2D antibody (CX5) on days 1, 5, and 8 after clinical onset and were monitored for 10 days.

Results

We demonstrated expression of NKG2D and its ligands on human RA synovial cells and extended this finding to the paws of arthritic mice. Expression of messenger RNA for the NKG2D ligand Rae‐1 was up‐regulated, and NKG2D was present predominantly on natural killer (NK) and CD4+ T cells, in arthritic paw cell isolates. NKG2D was down‐modulated during the progression of collagen‐induced arthritis (CIA). NKG2D expression in arthritic paws was demonstrated by immunohistochemistry. Blockade of NKG2D ameliorated established CIA, with significant reductions in clinical scores and paw swelling. Histologic analysis of arthritic joints from anti‐NKG2D–treated mice demonstrated significant joint protection, compared with control mice. Moreover, anti‐NKG2D treatment significantly reduced both interleukin‐17 production from CD4+ T cells in arthritic paws and splenic NK cell cytotoxic effector functions in vivo and in vitro.

Conclusion

Our findings indicate that blockade of NKG2D in a murine model and in human explants has beneficial therapeutic potential that merits further investigation in RA.
A continuous cell alkaline lysis, neutralization, and clarification combination process for production of plasmid pUDK‐HGF
Authors: Chunsheng Hu , Qinglin Zhang , Yuxin Lu , Xiaochen Cheng , Yanliang Wang , Tong Zhang , Zuze Wu
Published: May 2011

Plasmid DNA for biopharmaceutical applications is produced easily in Escherichia coli bacteria. The cell lysis is the most crucial step for purification of plasmid DNA. In this paper, we describe a continuous cell alkaline lysis, neutralization, and clarification combination process for production of plasmid pUDK‐HGF using hollow fiber ultrafiltration column as a lysis chamber and compare the plasmid DNA yield and homogeneity with the T‐connector and manual processes, respectively. The results show that the plasmid pUDK‐HGF yield of the combination process is 13% higher than manual lysis, twice higher than using T‐connector. When the proportion of lysed cells and neutralization solution is 3:1, the plasmid pUDK‐HGF yield can improve by 70%. This process could be easily scaled up to meet the industrial scale for cell lysis.
A genetic algorithm for the optimization of the thermoinduction protocol for high‐level production of recombinant human‐like collagen from Escherichia coli
Authors: Chi Lei , Fan Dai‐Di , Ma Xiao‐Xuan , Mi Yu , Luo Yan‐E , Zhu Chen‐Hui , Zhu Xiao‐Li , Xue Wen‐Jiao
Published: May 2011

Production of recombinant human‐like collagen (RHLC) by thermoinduction of recombinant Escherichia coli BL 21 during high cell density cultivation was investigated in a 30 L bioreactor. The effects of induction temperature (T), pH, and carbon‐to‐nitrogen molar ratio of the nutrient medium (C/N) were examined. The optimal thermoinduction protocol for RHLC production was determined by using a model coupling genetic algorithm and artificial neural networks. The optimal operating conditions were as follows: maintenance of induction temperature at 42°C for 3 H and then at 39.4°C until the end, induction pH at 7.03, and C/N at 4.8 (mol/mol). The theoretical maximum concentration of RHLC was 12.5 g/L, whereas the experimental value was 12.1 g/L under the optimal induction conditions.
An industrial perspective on bioreactor scale‐down: What we can learn from combined large‐scale bioprocess and model fluid studies
Authors: Noorman Henk
Published: May 2011

For industrial bioreactor design, operation, control and optimization, the scale‐down approach is often advocated to efficiently generate data on a small scale, and effectively apply suggested improvements to the industrial scale. In all cases it is important to ensure that the scale‐down conditions are representative of the real large‐scale bioprocess. Progress is hampered by limited detailed and local information from large‐scale bioprocesses. Complementary to real fermentation studies, physical aspects of model fluids such as air‐water in large bioreactors provide useful information with limited effort and cost. Still, in industrial practice, investments of time, capital and resources often prohibit systematic work, although, in the end, savings obtained in this way are trivial compared to the expenses that result from real process disturbances, batch failures, and non‐flyers with loss of business opportunity. Here we try to highlight what can be learned from real large‐scale bioprocess in combination with model fluid studies, and to provide suitable computation tools to overcome data restrictions. Focus is on a specific well‐documented case for a 30‐m3 bioreactor. Areas for further research from an industrial perspective are also indicated.
Fast and easy protocol for the purification of recombinant S‐layer protein for synthetic biology applications
Authors: Norville Julie E. , Kelly Deborah F. , Knight Thomas F. , Belcher Angela M. , Walz Thomas
Published: May 2011

A goal of synthetic biology is to make biological systems easier to engineer. One of the aims is to design, with nanometer‐scale precision, biomaterials with well‐defined properties. The surface‐layer protein SbpA forms 2D arrays naturally on the cell surface of Lysinibacillus sphaericus, but also as the purified protein in solution upon the addition of divalent cations. The high propensity of SbpA to form crystalline arrays, which can be simply controlled by divalent cations, and the possibility to genetically alter the protein, make SbpA an attractive molecule for synthetic biology. To be a useful tool, however, it is important that a simple protocol can be used to produce recombinant wild‐type and modified SbpA in large quantities and in a biologically active form. The present study addresses this requirement by introducing a mild and non‐denaturing purification protocol to produce milligram quantities of recombinant, active SbpA.
Selective detection of gold using genetically engineered bacterial reporters
Authors: Cerminati Sebastián , Soncini Fernando C. , Checa Susana K.
Published: May 2011

Salmonella typhimurium harbours a Au‐resistance system whose expression is controlled by GolS, a transcriptional regulator of the MerR family that selectively detects Au with high sensitivity. We developed both Salmonella and genetically engineered Escherichia coli strains as Au‐selective whole‐cell biosensors by coupling the strictly regulated GolS‐dependent golB promoter to the gfp reporter gene. The bio‐reporters were evaluated under different laboratory conditions and calibrated for their use as selective Au detectors. Due to the intrinsic characteristics of the regulatory protein, the transgenic E. coli sensor exhibits low background, high signal‐to‐noise ratio, and improved sensitivity for detection of Au ions in a wide range of concentrations (up to 470 nM) with a calculated detection limit of ∼33 nM (6 µg L−1 or parts per billion) Au(I). The fluorescent Au‐sensing bacteria exhibit also minimal interference by chemically related metals such as Cu or Ag that are commonly found in Au deposits. These highly specific and sensitive Au detectors might allow the development of rapid and robust screening tools to improve discovery and extraction procedures. Biotechnol. Bioeng. 2011;108: 2553–2560. © 2011 Wiley Periodicals, Inc.
Developing a compound‐specific receptor for bisphenol a by directed evolution of human estrogen receptor α
Authors: Rajasärkkä Johanna , Hakkila Kaisa , Virta Marko
Published: May 2011

Directed evolution has become a successful approach to alter ligand binding properties of nuclear receptors. In this study, directed evolution was used to generate a mutant human estrogen receptor α library, which was then used to screen for receptors having enhanced responses to the known endocrine‐disrupting chemical, bisphenol A (BPA). A single round of multi‐site mutation was combined with an efficient positive/negative library screening method in which positive growth‐based selection for the desired activity with BPA was combined with flow cytometric removal of cells having undesired activity with the natural ligand, 17β‐estradiol. The screening steps were performed in a Saccharomyces cerevisiae yeast strain containing a genome‐integrated his3‐yEGFP reporter gene fusion construct. A single round of mutation and screening yielded nine mutants with enhanced responses towards BPA but no detectable induction by 17β‐estradiol (up to 90 nM). These BPA‐specific mutant receptors may prove useful in the field of environmental analytics, where they could be used to monitor and evaluate the proportion of BPA in hormonally active samples. Biotechnol. Bioeng. 2011;108: 2526–2534. © 2011 Wiley Periodicals, Inc.
Metabolic adaptation of MDCK cells to different growth conditions: Effects on catalytic activities of central metabolic enzymes
Authors: Janke R. , Genzel Y. , Händel N. , Wahl A. , Reichl U.
Published: May 2011

Lactate and ammonia are the most important waste products of central carbon metabolism in mammalian cell cultures. In particular during batch and fed‐batch cultivations these toxic by‐products are excreted into the medium in large amounts, and not only affect cell viability and productivity but often also prevent growth to high cell densities. The most promising approach to overcome such a metabolic imbalance is the replacement of one or several components in the culture medium. It has been previously shown that pyruvate can be substituted for glutamine in cultures of adherent Madin–Darby canine kidney (MDCK) cells. As a consequence, the cells not only released no ammonia but glucose consumption and lactate production were also reduced significantly. In this work, the impact of media changes on glucose and glutamine metabolism was further elucidated by using a high‐throughput platform for enzyme activity measurements of mammalian cells. Adherent MDCK cells were grown to stationary and exponential phase in six‐well plates in serum‐containing GMEM supplemented with glutamine or pyruvate. A total number of 28 key metabolic enzyme activities of cell extracts were analyzed. The overall activity of the pentose phosphate pathway was up‐regulated during exponential cell growth in pyruvate‐containing medium suggesting that more glucose‐6‐phosphate was channeled into the oxidative branch. Furthermore, the anaplerotic enzymes pyruvate carboxylase and pyruvate dehydrogenase showed higher cell specific activities with pyruvate. An increase in cell specific activity was also found for NAD+‐dependent isocitrate dehydrogenase, glutamate dehydrogenase, and glutamine synthetase in MDCK cells grown with pyruvate. It can be assumed that the increase in enzyme activities was required to compensate for the energy demand and to replenish the glutamine pool. On the other hand, the activities of glutaminolytic enzymes (e.g., alanine and aspartate transaminase) were decreased in cells grown with pyruvate, which seems to be related to a decreased glutamine metabolism. Biotechnol. Bioeng. 2011;108: 2691–2704. © 2011 Wiley Periodicals, Inc.
Controlling glycation of recombinant antibody in fed‐batch cell cultures
Authors: Yuk Inn H. , Zhang Boyan , Yang Yi , Dutina George , Leach Kimberly D. , Vijayasankaran Natarajan , Shen Amy Y. , Andersen Dana C. , Snedecor Bradley R. , Joly John C.
Published: May 2011

Protein glycation is a non‐enzymatic glycosylation that can occur to proteins in the human body, and it is implicated in the pathogenesis of multiple chronic diseases. Glycation can also occur to recombinant antibodies during cell culture, which generates structural heterogeneity in the product. In a previous study, we discovered unusually high levels of glycation (>50%) in a recombinant monoclonal antibody (rhuMAb) produced by CHO cells. Prior to that discovery, we had not encountered such high levels of glycation in other in‐house therapeutic antibodies. Our goal here is to develop cell culture strategies to decrease rhuMAb glycation in a reliable, reproducible, and scalable manner. Because glycation is a post‐translational chemical reaction between a reducing sugar and a protein amine group, we hypothesized that lowering the concentration of glucose—the only source of reducing sugar in our fed‐batch cultures—would lower the extent of rhuMAb glycation. When we decreased the supply of glucose to bioreactors from bolus nutrient and glucose feeds, rhuMAb glycation decreased to below 20% at both 2‐L and 400‐L scales. When we maintained glucose concentrations at lower levels in bioreactors with continuous feeds, we could further decrease rhuMAb glycation levels to below 10%. These results show that we can control glycation of secreted proteins by controlling the glucose concentration in the cell culture. In addition, our data suggest that rhuMAb glycation occurring during the cell culture process may be approximated as a second‐order chemical reaction that is first order with respect to both glucose and non‐glycated rhuMAb. The basic principles of this glycation model should apply to other recombinant proteins secreted during cell culture. Biotechnol. Bioeng. 2011;108: 2600–2610. © 2011 Wiley Periodicals, Inc.
Optimizing antiplatelet therapy in acute coronary syndrome and percutaneous coronary intervention
Authors: Faxon David P.
Published: May 2011

Dual antiplatelet therapy with aspirin and clopidogrel is the standard of care for patients with acute coronary syndrome (ACS) and those undergoing percutaneous coronary intervention (PCI). It is well established that inhibition of platelet aggregation reduces the risk of recurrent thrombotic events and stent thrombosis. However, some patients show a reduced antiplatelet response to standard clopidogrel loading (300 mg) and maintenance (75 mg day−1) doses, which has been associated with poorer patient outcomes. Pharmacodynamic and pharmacokinetic studies show that higher‐than‐standard clopidogrel dosing strategies facilitate more rapid platelet inhibition of a greater intensity as a result of greater plasma concentrations of the clopidogrel active metabolite. Recently completed studies suggest that in patients with ACS undergoing PCI, higher‐than‐standard clopidogrel dosing regimens provide greater inhibition of platelet function and improved clinical outcomes with a small but significant increase in major bleeding. Newer, more potent antiplatelet agents such as prasugrel and ticagrelor are other alternative strategies that result in more rapid, greater inhibition of platelet function and better outcomes than standard‐dose clopidogrel. Whether platelet reactivity‐guided therapy or genotyping for cytochrome P450 polymorphisms is useful in managing patients needs to be further defined. Most importantly, early and effective antiplatelet therapy results in the best short‐ and long‐term outcomes for patients with ACS or those undergoing PCI. © 2011 Wiley‐Liss, Inc.
High Fidelity Self‐Recognition of Isomeric Oligopyridines in Binary 2D Self‐Assembly and Its Application for Separation
Authors: Caterbow Daniel , Roos Matthias , Hoster Harry E. , Behm R. Jürgen , Landfester Katharina , Ziener Ulrich
Published: May 2011

Self‐assembly in two binary mixtures based on three isomeric oligopyridines at the liquid/HOPG (highly oriented pyrolytic graphite) interface is presented. Despite their structural similarity the molecules display exclusive phase separation, which is attributed to the highly specific intermolecular hydrogen bonding interactions. Variation of the mole fractions in solution reveal strongly preferred adsorption of the major compound, which underlines the importance of self‐recognition for self‐assembly. Those findings at the molecular level can be applied to separation issues on a macroscopic scale, leading to a completely new concept of separation, which could have a strong impact on various chromatographic processes.
Development of a Flexible Strategy towards FR900482 and the Mitomycins
Authors: Trost Barry M. , O'Boyle Brendan M. , Torres Wildeliz , Ameriks Michael K.
Published: May 2011

FR900482 and the mitomycins are two intriguing classes of alkaloid natural products that have analogous biological mechanisms and obvious structural similarity. Both classes possess potent anticancer activity, a feature that has led to their investigation and implementation for the clinical treatment of human cancer. Given the structural similarity between these natural products, we envisioned a common synthetic strategy by which both classes could be targeted through assembling the mitomycin skeleton prior to further oxidative functionalization. Realization of this strategy with respect to FR900482 was accomplished through the synthesis of 7‐epi‐FR900482, which displayed equal potency relative to the natural product against two human cancer cell lines. With the challenging goal of a synthesis of either mitomycin or FR900482 in mind, several methodologies were explored. While not all of these methods ultimately proved useful for our synthetic goal, a number of them led to intriguing findings that provide a more complete understanding of several methodologies. In particular, amination via π‐allyl palladium complexes for the synthesis of tetrahydroquinolines, eight‐membered heterocycle formation via carbonylative lactamization, and amination through late‐stage CH insertion via rhodium catalysis all featured prominently in our synthetic studies.
Self‐Assembly Into Spheres of a Hybrid Diphenylalanine–Porphyrin: Increased Fluorescence Lifetime and Conserved Electronic Properties
Authors: Charalambidis Georgios , Kasotakis Emmanouil , Lazarides Theodore , Mitraki Anna , Coutsolelos Athanassios G.
Published: May 2011

A series of protected phenylalanine and diphenylalanine derivatives have been coupled through a peptide bond to a monoaminoporphyrin to form new materials. A comparative study in solution and in the solid state has been performed and confirmed new and interesting properties for the self‐assembled hybrid materials while conserving the electronic properties of the chromophore. Thus, they are powerful candidates for use in dye‐sensitized solar cells.
Fibrous architectures and organogels of tris(phenylethynylphenyl)adamantane molecules with amino acid moieties: Their solvato‐controlled helicity induction
Authors: Tominaga Masahide , Azumaya Isao
Published: May 2011

Non‐disk‐shaped molecules self‐assembled to form columnar‐type helical aggregates with gel ability through π‐stacking interactions among the central tris(phenylethynylphenyl)adamantane moieties, hydrogen‐bonding interactions among the alanine parts with amide groups, and van der Waals interactions among the alkyl groups in nonpolar n‐alkanes. The structural analyses of fibrous architectures with helicity were examined by FTIR, UV‐Vis, and circular dichroism (CD) spectroscopy and FE‐SEM measurements. In contrast, the formation of fibrous structures was observed from adamantane‐based tripodal molecules due to solvophobic interactions in polar EtOH, which showed no detectable Cotton effect in the CD measurement, indicating the induction of solvato‐controlled helicity in the self‐assembly process. Chirality 2011. © 2011 Wiley Periodicals, Inc.
Highly Dispersed MoO3/Al2O3 Shell‐Core Composites Synthesized by CVD of Mo(CO)6 under Atmospheric Pressure
Authors: Shi Guojun , Franzke Thomas , Xia Wei , Sanchez Miguel D. , Muhler Martin
Published: May 2011

MoO3/γ‐Al2O3 composites are synthesized by CVD under atmospheric pressure using Mo(CO)6 as the precursor and porous γ‐Al2O3 particles in a horizontal, rotating, hot‐wall reactor, which is also used for calcination in air. The composites are characterized by N2 physisorption, atomic absorption spectroscopy, X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), transmission electron microscopy (TEM), and laser Raman spectroscopy (LRS). The synthesized samples exhibit excellent porosity, even at high Mo loadings. A much higher Mo yield is achieved when applying sublimation‐adsorption in static air instead of using flowing N2. A high degree of Mo dispersion on alumina is confirmed by XRD, LRS, and TEM; with a Mo surface density as high as 5.2 atoms nm−2, the sample is X‐ray amorphous, there are no polymeric molybdate species detectable by LRS, and the island size of the molybdate species is about 1 nm according to TEM. The XPS analysis shows that exclusively MoVI species are present on all synthesized samples. Thus, the applied rotating, hot‐wall reactor achieves efficient mixing and homogeneous deposition.
Periductal mastitis in a male breast masquerading as lobular carcinoma on fine needle aspiration cytology
Authors: Gupta Nalini , Agrawal Pallavi , Saikia Uma Nahar , Das Ashim , Srinivasan Radhika , Rajwanshi Arvind , Singh Gurpreet
Published: May 2011

Fine needle aspiration cytology (FNAC) is quite successful in identifying specific benign and malignant breast lesions, but its role in the categorization of proliferative breast lesions has not been well defined. Mastitis/ breast abscess can lead to intense inflammatory response; however, its association with epithelial hyperplasia is rarely reported. At times, it may be difficult to differentiate dense lymphoplasmacytic infiltrate from non‐Hodgkin's lymphoma. We present a case of periductal mastitis associated with epithelial hyperplasia, presenting as a subaerolar swelling in a male breast, which was misinterpreted as lobular carcinoma on FNAC. Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc.
Histomorphological study of palatal shelf elevation during murine secondary palate formation
Authors: Yu Kai , Ornitz David M.
Published: May 2011

During mammalian secondary palate development, the palatal shelves undergo dramatic morphological changes to elevate from a vertical to a horizontal plane in the oral‐nasal cavity. We found that E14.5 mouse embryos displayed marked variations in shelf morphology that represent various intermediate states of the elevation process. With these variations, we reconstructed the sequence of shelf morphological changes that take place during the elevation process and discovered distinct patterns in different regions along the anterior‐posterior (AP) axis. Moreover, our study revealed that during the elevation process, shelf morphological changes are accompanied by tongue morphological changes, which also show distinct characteristics along the AP axis. We further discuss how to divide the palate along the AP axis based on morphological criteria. Our study provides a framework that recognizes variation in timing of palatal morphogenesis along the AP axis that will aid in the investigation of the mechanisms regulating palatal shelf elevation. Developmental Dynamics 240:1737–1744, 2011. © 2011 Wiley‐Liss, Inc.
Synthesis, Structure, and Thermoelectric Properties of Barium Copper Polychalcogenides with Chalcogen‐Centered Cu Clusters and Te22– Dumbbells
Authors: Mayasree Oottil , Sankar Cheriyedath Raj , Cui Yanjie , Assoud Abdeljalil , Kleinke Holger
Published: May 2011

BaCu6–xSTe6 and BaCu6–xSe1–yTe6+y were synthesized from the elements at 663 K. These chalcogenides adopt a new structure type, cubic space group Pm$\bar {3}$, with a = 6.9680(2) Å in the case of BaCu5.93SeTe6. Therein, the Cu atoms form cubic clusters, centered by Se atoms, where statistically 2.07 corners are unoccupied. All Te atoms are part of Te22– dumbbells, leading to a charge‐balanced formula when x = 0: Ba2+(Cu+)6Se2–(Te22–)3. While Te atoms can be incorporated on the Se site, no evidence was found for the ability of Se atoms to replace Te in the Te22– pairs. Band structure calculations on different BaCu6SeTe6 models revealed a very small band gap at the Fermi level; all these chalcogenides with x > 0 should thus be p‐doped semiconductors, which we experimentally confirmed for BaCu5.7Se0.6Te6.4.
Versatile Zirconium Reductants and Carbon–Carbon Coupling Agents Selectively Accessible from the 2:1 Molar Aggregate of n‐Butyllithium and Zirconium(IV) Salts
Authors: Eisch John J. , Gitua John N. , Yu Kun
Published: May 2011

In previous studies of transition metal alkyls the 2:1 molar aggregate of n‐butyllithium and zirconium(IV) salts has been found to react both with benzylic hydrocarbons and aromatic carbonyl derivatives in diverse and useful ways. In the present study the reactions of the aggregates, 2nBuLi·ZrE4 (E = Cl, OEt), with benzaldehyde have involved carbometallation, hydrometallation and reductive dimerization (paths 1–3) in THF and were selectively achievable by temperature control alone. First, at –78 °C benzaldehyde underwent carbolithiation to give upon hydrolysis 1‐phenyl‐1‐pentanol. However, short‐term reaction times and prompt D2O quenching revealed that with Zr(OEt)4 both benzaldehyde and 1‐phenyl‐1‐pentanol were deuteriated, consistent with the presence of a phenyl(lithioxy)carbene intermediate. The observed dimerization of benzaldehyde to benzyl benzoate by lithium 2,2,6,6‐tetramethylpiperidide is also consistent with such a phenyl(lithioxy)carbene intermediate. Second, at 25 °C the 2nBuLi·ZrE4 aggregate reduced benzaldehyde exclusively to benzyl alcohol, which observation is consistent with the formation of the hydrozirconating agent, H2ZrE2. Third, heating the aggregate at reflux and subsequent reaction with benzaldehyde produced solely the reduced dimer, 1,2‐diphenyl‐1,2‐ethanediol with high stereoselectivity: E = Cl, rac/meso of 93:7 and E = OEt, rac/meso of 100:0. The proposed mechanism involves the formation of ZrE2, the epizirconation of benzaldehyde and the insertion of the second benzaldehyde into the zirconaoxacyclopropane under steric control. Finally, the high selectivity in hydrozirconation and reductive dimerization shown by 2nBuLi·ZrE4 appears at this time to be superior to that attainable with analogous titanium or hafnium aggregates.
Neural basis of the association between depressive symptoms and memory deficits in nondemented subjects: resting‐state fMRI study
Authors: Xie Chunming , Goveas Joseph , Wu Zhilin , Li Wenjun , Chen Guangyu , Franczak Malgorzata , Antuono Piero G. , Jones Jennifer L. , Zhang Zhijun , Li Shi‐Jiang
Published: May 2011

Depressive symptoms often coexist with memory deficits in older adults and also are associated with incident cognitive decline in the elderly. However, little is known about the neural correlates of the association between depressive symptoms and memory deficits in nondemented elderly. Fifteen amnestic mild cognitive impairment (aMCI) and 20 cognitively normal (CN) subjects completed resting‐state functional magnetic resonance imaging (R‐fMRI) scans. Multiple linear regression analysis was performed to test the main effects of the Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test delayed recall (RAVLT‐DR) scores, and their interaction on the intrinsic amygdala functional connectivity (AFC) network activity. Severer depressive symptoms and memory deficits were found in the aMCI group than in the CN group. Partial correlation analysis identified that the RAVLT‐DR scores were significantly correlated with the AFC network in the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial and anterior prefrontal cortex, posterior cingulate cortex (PCC), middle occipital gyrus, right inferior parietal cortex, and left middle temporal gyrus (MTG). The GDS scores were positively correlated with the AFC network in the bilateral PCC and MTG, and left DLPFC. The interactive effects of the GDS and RAVLT‐DR scores on the AFC network were seen in the bilateral PCC, MTG, and left DLPFC. These findings not only supported that there were interactive neural links between depressive symptoms and memory functions in nondemented elderly at the system level, but also demonstrated that R‐fMRI has advantages in investigating the interactive nature of different neural networks involved in complex functions, such as emotion and cognition. Hum Brain Mapp , 2011. © 2011 Wiley‐Liss, Inc.
fMRI investigation of speed–accuracy strategy switching
Authors: Vallesi Antonino , McIntosh Anthony R. , Crescentini Cristiano , Stuss Donald T.
Published: May 2011

Switching between rapid and accurate responses is an important aspect of decision‐making. However, the brain mechanisms important to smoothly change the speed–accuracy strategy remain mostly unclear. This issue was addressed here by using functional magnetic resonance imaging (fMRI). On each trial, right‐handed healthy participants had to stress speed or accuracy in performing a color discrimination task on a target stimulus according to the instructions given by an initial cue. Participants were capable of trading speed for accuracy and vice versa. Analyses of cue‐related fMRI activations revealed a significant recruitment of left middle frontal gyrus and right cerebellum when switching from speed to accuracy. The left superior parietal lobule was activated in the same switching condition but only after the target onset. The anterior cingulate cortex was more recruited, also after target presentation, when speed had to be maintained from one trial to the next. These results are interpreted within a theoretical framework that attributes a role in criterion‐setting to the left lateral prefrontal cortex, perceptual evidence accumulation to the superior parietal lobule, and action energization to the anterior cingulate cortex, extending previous findings to the domain of speed–accuracy tradeoff regulations. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.