bluuebunny/crossref_metadata_2025 huggingface dataset:
Swine‐origin pandemic H1N1 influenza virus‐like particles produced in insect cells induce hemagglutination inhibiting antibodies in BALB/c mice
Authors: Krammer Florian , Nakowitsch Sabine , Messner Paul , Palmberger Dieter , Ferko Boris , Grabherr Reingard
Published: December 2009

Recent outbreaks of influenza A highlight the importance of rapid and sufficient supply for pandemic and inter‐pandemic vaccines. Classical manufacturing methods for influenza vaccines fail to satisfy this demand. Alternatively, cell culture‐based production systems and virus‐like particle (VLP)‐based technologies have been established. We developed swine‐origin pandemic H1N1 influenza VLPs consisting of hemagglutinin (A/California/04/2009) and matrix protein. Hemagglutinin and matrix protein were co‐expressed in insect cells by the baculovirus expression system. VLPs were harvested from infection supernatants, purified and used for intraperitoneal immunization of BALB/c mice. Immunization induced high serum antibody titers against A/California/04/2009 as well as hemagglutination inhibiting antibodies. Additionally, we compared VLP production in two different insect cell lines, Sf9 and BTI‐TN5B1‐4 (High Five™). Taken together VLPs represent a potential strategy for the fight against new pandemic influenza viruses.
Effects of culture conditions on N‐glycolylneuraminic acid (Neu5Gc) content of a recombinant fusion protein produced in CHO cells
Authors: Borys Michael C. , Dalal Nimish G. , Abu‐Absi Nicholas R. , Khattak Sarwat F. , Jing Ying , Xing Zizhuo , Li Zheng Jian
Published: December 2009

CHO cells express glycoproteins containing both the N‐acetylneuraminic acid (Neu5Ac) and minor amounts of the N‐glycolylneuraminic acid (Neu5Gc) forms of sialic acid. As Neu5Gc is not expressed in humans and can be recognized as a foreign epitope, there is the potential for immunogenicity issues for glycoprotein therapeutics. During process development of a glycosylated fusion protein expressed by CHO cells, a number of culture conditions were identified that affected the Neu5Gc content of the recombinant glycoprotein. Sodium butyrate (SB), a well‐known additive reported to enhance recombinant protein productivity in specific cases, minimally affected product titers here, but did decrease Neu5Gc levels by 50–62%. A shift in culture temperature to a lower value after the exponential growth phase was used to extend the culture period. It was found that the Neu5Gc levels were 59% lower when the temperature shift occurred later near the stationary phase of the culture compared to an early‐temperature shift, near the end of the exponential growth phase. Studies on the effects of pCO2 with this product showed that the Neu5Gc levels were 46% lower at high pCO2 conditions (140 mmHg) compared to moderate pCO2 levels (20–80 mmHg). Finally, a comparison of sodium carbonate versus sodium hydroxide as the base used for pH control resulted in a reproducible 33% decrease in Neu5Gc in bioreactors using sodium hydroxide. These results are of practical importance as SB is a commonly tested additive, and the other factors affecting Neu5Gc can conveniently be used to reduce or control Neu5Gc in processes for the manufacture of glycoprotein therapeutics. Biotechnol. Bioeng. 2010;105: 1048–1057. © 2009 Wiley Periodicals, Inc.
Development of a multiresidue method for the determination of multiclass pesticides in soil using GC
Authors: Park Jong‐Hyouk , Mamun Md. Iqbal Rouf , Choi Jeong‐Heui , Abd El‐Aty A. M. , Assayed M. E. , Choi Woo Jung , Yoon Kwang Sik , Han Seong‐Soo , Kim Hee Kweon , Park Byung Jun , Kim Kap Soon , Kim Sang Don , Choi Hun Geun , Shim Jae‐Han
Published: December 2009

The principal objective of the present study was to develop a multiresidue analytical method for 62 pesticides in a soil matrix. Soil samples were fortified with known quantities of pesticides at two different concentration levels (0.1 and 0.01 μg/g) and the analytes were extracted via a liquid–solid extraction method. The pesticides were separated on an HP5 capillary column and were detected by gas chromatography coupled to an electron capture detector (GC‐ECD). The method was validated, considering its good linearities (r2 = 0.978–0.999), specificity and recovery characteristics. Recoveries were found between 70.3 and 113.4% for all pesticides except edifenphos (67.5%) and dichlobenil (69.5%) spiked at a 0.1 μg/mL concentration level and 74.5–117% except ethalfluralin (63.3%) and dichlobenil (51.9%) spiked at a concentration of 0.01 μg/mL. The developed method could be utilized as a simple and cost‐effective method for the routine analysis of 62 pesticides in soil samples. Copyright © 2009 John Wiley & Sons, Ltd.
A multiparallel bioreactor for the cultivation of mammalian cells in a 3D‐ceramic matrix
Authors: Goralczyk Vicky , Driemel Gregor , Bischof Andreas , Peter Andrea , Berthold Almuth , Kroh Lothar , Blessing Lucienne , Schubert Helmut , King Rudibert
Published: December 2009

For adherently growing cells, cultivation is limited by the provided growth surface. Excellent surface‐to‐volume ratios are found in highly porous matrices, which have to face the challenge of nutrient supply inside the matrices' caverns. Therefore, perfusion strategies are recommended which often have to deal with the need of developing an encompassing bioreactor periphery. We present a modular bioreactor system based on a porous ceramic matrix that enables the supply of cells with oxygen and nutrients by perfusion. The present version of the reactor system focuses on simple testing of various inoculation and operation modes. Moreover, it can be used to efficiently test different foam structures. Protocols are given to set‐up the system together with handling procedures for long‐time cultivation of a CHO cell line. Experimental results confirm vital growth of cells inside the matrices' caverns. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Techno‐economic evaluation of a two‐step biological process for hydrogen production
Authors: Ljunggren Mattias , Zacchi Guido
Published: December 2009

An integrated biological process for the production of hydrogen based on thermophilic and photo‐heterotrophic fermentation was evaluated from a technical and economic standpoint. Besides the two fermentation steps the process also includes pretreatment of the raw material (potato steam peels) and purification of hydrogen using amine absorption. The study aimed neither at determining the absolute cost of biohydrogen nor at an economic optimization of the production process, but rather at studying the effects of different parameters on the production costs of biohydrogen as a guideline for future improvements. The effect of the key parameters, hydrogen productivity and yield and substrate concentration in the two fermentations on the cost of the hydrogen produced was studied. The selection of the process conditions was based mainly on laboratory data. The process was simulated by use of the software Aspen Plus and the capital costs were estimated using the program Aspen Icarus Process Evaluator. The study shows that the photo‐fermentation is the main contributor to the hydrogen production cost mainly because of the cost of plastic tubing, for the photo‐fermentors, which represents 40.5% of the hydrogen production cost. The costs of the capital investment and chemicals were also notable contributors to the hydrogen production cost. Major economic improvements could be achieved by increasing the productivity of the two fermentation steps on a medium‐term to long‐term scale. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Using the rate of respiration to monitor events in the infection of Escherichia coli cultures by bacteriophage T4
Authors: Sauvageau Dominic , Allain Béatrice , Cooper David G.
Published: December 2009

The growing interest in applications of bacteriophages creates a need for improvements in the production processes. Continuous monitoring of the phage production is an essential aspect of any control strategy and, at present, there is no completely satisfactory option. The approach presented here uses IR‐spectrometry to continuously measure the rate of respiration (CO2 released) of Escherichia coli infected by phage T4 at various multiplicities of infection (MOI). Within the trends in these data, or in other aspects of the rate of respiration, it was possible to reliably and reproducibly identify five features that reflected specific events in the infection process. These included two events in the host cell apparent growth rate and events in the magnitude of the host cell density, in the measurement of OD600 or in the specific rate of respiration. All of these correlations were within 95% confidence showing that they are suitable for the monitoring and control of E. coli populations infected by phage T4. This method is reliable, cheap, and can be operated in‐line and in real time. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Switchgrass leaching requirements for solid‐state fermentation by Acidothermus cellulolyticus
Authors: VanderGheynst Jean S. , Rezaei Farzaneh , Dooley Todd M. , Berry Alison M.
Published: December 2009

Growth of Acidothermus cellulolyticus in solid‐state fermentation and its required growth conditions were investigated in this study. Extraction of switchgrass was required for growth. Under the experimental conditions, extraction ratio had the most significant effect on the growth of A. cellulolyticus. Heat treatment (in the form of autoclaving) of switchgrass did not have a significant effect on the growth rate; however, longer heat treatment times had a negative effect on the total growth. Moisture content adjustment had no effect on the release of inhibitors into extracts. Our results showed that leaching at a minimum 40:1 (gram water: gram dry biomass) removed inhibitory compound(s) from switchgrass. Upon extraction A. cellulolyticus colonized switchgrass in solid fermentation without exogenous addition of carbon and nitrogen sources. It is the first demonstration of growth of A. cellulolyticus in solid fermentation. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
pH measurement and a rational and practical pH control strategy for high throughput cell culture system
Authors: Zhou Haiying , Purdie Jennifer , Wang Tongtong , Ouyang Anli
Published: December 2009

The number of therapeutic proteins produced by cell culture in the pharmaceutical industry continues to increase. During the early stages of manufacturing process development, hundreds of clones and various cell culture conditions are evaluated to develop a robust process to identify and select cell lines with high productivity. It is highly desirable to establish a high throughput system to accelerate process development and reduce cost. Multiwell plates and shake flasks are widely used in the industry as the scale down model for large‐scale bioreactors. However, one of the limitations of these two systems is the inability to measure and control pH in a high throughput manner. As pH is an important process parameter for cell culture, this could limit the applications of these scale down model vessels. An economical, rapid, and robust pH measurement method was developed at Eli Lilly and Company by employing SNARF‐4F 5‐(‐and 6)‐carboxylic acid. The method demonstrated the ability to measure the pH values of cell culture samples in a high throughput manner. Based upon the chemical equilibrium of CO2, HCO, and the buffer system, i.e., HEPES, we established a mathematical model to regulate pH in multiwell plates and shake flasks. The model calculates the required %CO2 from the incubator and the amount of sodium bicarbonate to be added to adjust pH to a preset value. The model was validated by experimental data, and pH was accurately regulated by this method. The feasibility of studying the pH effect on cell culture in 96‐well plates and shake flasks was also demonstrated in this study. This work shed light on mini‐bioreactor scale down model construction and paved the way for cell culture process development to improve productivity or product quality using high throughput systems. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Disaggregation of high‐molecular weight species during downstream processing to recover functional monomer
Authors: Xu Xuankuo , Didio David M. , Leister Kirk J. , Ghose Sanchayita
Published: December 2009

The use of chaotropic agents to recover functional monomeric material was investigated for the downstream purification of an Fc‐fusion protein containing high levels of high‐molecular weight (HMW) species. In batch studies, chaotropic agents irreversibly disaggregated a majority of the aggregated protein. An integrated processing mode, termed as on‐column disaggregation, was developed in which the protein was captured on Protein A chromatography and then a chaotropic agent was used to simultaneously elute the bound protein and disaggregate the HMW species. On‐column disaggregation process resulted in protein recoveries of >95% and aggregation reduction of ∼50%. Analytical results are presented showing that the recovered monomeric material was comparable to the reference protein in biochemical, biophysical, and pharmacokinetic properties. The kinetic and molecular mechanisms governing protein aggregation and disaggregation will also be elucidated. For the Fc‐fusion protein studied here, incorporation of the disaggregation strategy in both batch and on‐column modes led to an increase of >10% in overall downstream yield. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
A cell leakproof PLGA‐collagen hybrid scaffold for cartilage tissue engineering
Authors: Kawazoe Naoki , Inoue Chieko , Tateishi Tetsuya , Chen Guoping
Published: December 2009

A cell leakproof porous poly(DL‐lactic‐co‐glycolic acid) (PLGA)‐collagen hybrid scaffold was prepared by wrapping the surfaces of a collagen sponge except the top surface for cell seeding with a bi‐layered PLGA mesh. The PLGA‐collagen hybrid scaffold had a structure consisting of a central collagen sponge formed inside a bi‐layered PLGA mesh cup. The hybrid scaffold showed high mechanical strength. The cell seeding efficiency was 90.0% when human mesenchymal stem cells (MSCs) were seeded in the hybrid scaffold. The central collagen sponge provided enough space for cell loading and supported cell adhesion, while the bi‐layered PLGA mesh cup protected against cell leakage and provided high mechanical strength for the collagen sponge to maintain its shape during cell culture. The MSCs in the hybrid scaffolds showed round cell morphology after 4 weeks culture in chondrogenic induction medium. Immunostaining demonstrated that type II collagen and cartilaginous proteoglycan were detected in the extracellular matrices. Gene expression analyses by real‐time PCR showed that the genes encoding type II collagen, aggrecan, and SOX9 were upregulated. These results indicated that the MSCs differentiated and formed cartilage‐like tissue when being cultured in the cell leakproof PLGA‐collagen hybrid scaffold. The cell leakproof PLGA‐collagen hybrid scaffolds should be useful for applications in cartilage tissue engineering. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Product and contaminant measurement in bioprocess development by SELDI‐MS
Authors: Berrill Alex , Ho Sa V. , Bracewell Daniel G.
Published: December 2009

Bioprocesses for therapeutic protein production typically require significant resources to be invested in their development. Underlying these efforts are analytical methods, which must be fit for the purpose of monitoring product and contaminants in the process. It is highly desirable, especially in early‐phase development when material and established analytical methods are limiting, to be able to determine what happens to the product and impurities at each process step with small sample volumes in a rapid and readily performed manner. This study evaluates the utility of surface‐enhanced laser desorption ionization mass spectroscopy (SELDI‐MS), known for its rapid analysis and minimal sample volumes, as an analytical process development tool. In‐process samples from an E. coli process for apolipoprotein A‐IM (ApoA‐IM) manufacture were used along with traditional analytical methods such as HPLC to check the SELDI‐MS results. ApoA‐IM is a naturally occurring variant of ApoA‐I that appears to confer protection against cardiovascular disease to those that carry the mutated gene. The results show that, unlike many other analytical methods, SELDI‐MS can handle early process samples that contain complex mixtures of biological molecules with limited sample pretreatment and thereby provide meaningful process‐relevant information. At present, this technique seems most suited to early‐phase development particularly when methods for traditional analytical approaches are still being established. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Impact of freezing on pH of buffered solutions and consequences for monoclonal antibody aggregation
Authors: Kolhe Parag , Amend Elizabeth , K. Singh Satish
Published: December 2009

Freezing of biologic drug substance at large scale is an important unit operation that enables manufacturing flexibility and increased use‐period for the material. Stability of the biologic in frozen solutions is associated with a number of issues including potentially destabilizing pH changes. The pH changes arise from temperature‐associated change in the pKas, solubility limitations, eutectic crystallization, and cryoconcentration. The pH changes for most of the common protein formulation buffers in the frozen state have not been systematically measured. Sodium phosphate buffer, a well‐studied system, shows the greatest change in pH when going from +25 to −30°C. Among the other buffers, histidine hydrochloride, sodium acetate, histidine acetate, citrate, and succinate, less than 1 pH unit change (increase) was observed over the temperature range from +25 to −30°C, whereas Tris‐hydrochloride had an ∼1.2 pH unit increase. In general, a steady increase in pH was observed for all these buffers once cooled below 0°C. A formulated IgG2 monoclonal antibody in histidine buffer with added trehalose showed the same pH behavior as the buffer itself. This antibody in various formulations was subject to freeze/thaw cycling representing a wide process (phase transition) time range, reflective of practical situations. Measurement of soluble aggregates after repeated freeze–thaw cycles shows that the change in pH was not a factor for aggregate formation in this case, which instead is governed by the presence or absence of noncrystallizing cryoprotective excipients. In the absence of a cryoprotectant, longer phase transition times lead to higher aggregation. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Predicting Muskingum flood routing parameters using spreadsheets
Authors: Karahan Halil
Published: December 2009

In this study, two easy to use and high precision solution methods that can be used for educational and engineering purposes are proposed. The first of these methods is the “Trial–Error with Spreadsheet” procedure combining basic properties of spreadsheets and the other method is the “Nonlinear optimization with Solver” procedure that uses the nonlinear optimization code and the “Iterative calculation” which is one of the most effective properties of spreadsheets. Both of the proposed methods are tested on three samples given in literature and the comparisons of the model results, observation results, and the results of other solution techniques in literature are made. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 20: 280–286, 2012
Using virtual platform in embedded system education
Authors: Lim Heuiseok , Yu HeonChang , Suh Taeweon
Published: December 2009

This article presents our cost‐effective curriculum on embedded systems. Education on embedded systems requires coverage of both hardware and software aspects of the systems. Our curriculum uses one monolithic environment, virtual platform, to introduce all the layers of the system components (i.e., from hardware to operating systems to user applications). It is cost‐effective since a hardware system is replaced by a virtual platform. Correspondingly, hardware boards and a lab space are not required. Yet, students are able to make modifications easily on hardware and software components of interest, fully exercising the system. Students responded to the course survey that they are knowledgeable on how embedded systems work after taking the course. Especially, students responded that the virtual platform is effective to use, in place of a hardware platform to learn embedded systems. The course materials are available to the public from a website at Korea University. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 20: 346–355, 2012
Uracil‐Catalyzed Synthesis of Acetyl Phosphate: A Photochemical Driver for Protometabolism
Authors: Hagan William J.
Published: December 2009

Progress toward a protometabolism (the earliest energy storage networks) has been severely hindered by a shortage of driver reactions, which could have harnessed solar photons or coupled electron sources/sinks on the primordial Earth. Here, it is reported for the first time that thioacetate can be converted into a known metabolite, acetyl phosphate, by ultraviolet light and in aqueous solution at neutral pH. Of more compelling importance, the synthesis is catalyzed by uracil, which suggests that a genetic component may have also facilitated the emergence of metabolic pathways. The chemistry of acetyl phosphate has been extensively studied, and it is known to be a precursor of phosphate esters, pyrophosphate and possibly longer inorganic chains. Moreover, its bifunctional reactivity (as either an acetyl or phosphoryl donor) would have been integral for the first metabolic cycles.
Ionic Liquids Based on Azolate Anions
Authors: Smiglak Marcin , Hines C. Corey , Wilson Timothy B. , Singh Shailendra , Vincek Adam S. , Kirichenko Kostyantyn , Katritzky Alan R. , Rogers Robin D.
Published: December 2009

Compartmentalized molecular level design of new energetic materials based on energetic azolate anions allows for the examination of the effects of both cation and anion on the physiochemical properties of ionic liquids. Thirty one novel salts were synthesized by pairing diverse cations (tetraphenylphosphonium, ethyltriphenylphosphonium, N‐phenyl pyridinium, 1‐butyl‐3‐methylimidazolium, tetramethyl‐, tetraethyl‐, and tetrabutylammonium) with azolate anions (5‐nitrobenzimidazolate, 5‐nitrobenzotriazolate, 3,5‐dinitro‐1,2,4‐triazolate, 2,4‐dinitroimidazolate, 4‐nitro‐1,2,3‐triazolate, 4,5‐dinitroimidazolate, 4,5‐dicyanoimidazolate, 4‐nitroimidazolate, and tetrazolate). These salts have been characterized by DSC, TGA, and single crystal X‐ray crystallography. The azolates in general are surprisingly stable in the systems explored. Ionic liquids were obtained with all combinations of the 1‐butyl‐3‐methylimidazolium cation and the heterocyclic azolate anions studied, and with several combinations of tetraethyl‐ or tetrabutylammonium cations and the azolate anions. Favorable structure–property relationships were most often achieved when changing from 4‐ and 4,5‐disubstituted anions to 3,5‐ and 2,4‐disubstituted anions. The most promising anion for use in energetic ionic liquids of those studied here, was 3,5‐dinitro‐1,2,4‐triazolate, based on its contributions to the entire set of target properties.
Self‐Assembly of Ureido‐Pyrimidinone Dimers into One‐Dimensional Stacks by Lateral Hydrogen Bonding
Authors: Nieuwenhuizen Marko M. L. , de Greef Tom F. A. , van der Bruggen Rob L. J. , Paulusse Jos M. J. , Appel Wilco P. J. , Smulders Maarten M. J. , Sijbesma Rint P. , Meijer E. W.
Published: December 2009

Ureido‐pyrimidinone (UPy) dimers substituted with an additional urea functionality self‐assemble into one‐dimensional stacks in various solvents through lateral non‐covalent interactions. 1H NMR and DOSY studies in CDCl3 suggest the formation of short stacks (<10), whereas temperature‐dependent circular dichroism (CD) studies on chiral UPy dimers in heptane show the formation of much larger helical stacks. Analysis of the concentration‐dependent evolution of chemical shift in CDCl3 and the temperature‐dependent CD effect in heptane suggest that this self‐assembly process follows an isodesmic pathway in both solvents. The length of the aggregates is influenced by substituents attached to the urea functionality. In sharp contrast, UPy dimers carrying an additional urethane group do not self‐assemble into ordered stacks, as is evident from the absence of a CD effect in heptane and the concentration‐independent chemical shift of the alkylidene proton of the pyrimidinone ring in CDCl3.
Cluster‐Based Self‐Assembly Route toward MoO3 Single‐Walled Nanotubes
Authors: Hu Shi , Ling Xi , Lan Tian , Wang Xun
Published: December 2009

MoO3 has a unique rigid double‐layer structure, which makes it a real challenge to prepare nanotubular structures. The controlled synthesis of MoO3 single‐walled nanotubes (SWNTs) is achieved through a cluster‐based self‐assembly route on the dodecanethiol/water interface. Various factors are studied at length, including precursor type, reaction time, temperature, pH value, and their influence on the morphology of products. The concept of “self‐assembly—from simple clusters to nanostructures” is proposed here based on preliminary results from the synthesis of MoO3 SWNTs, which provides a new aspect for traditional synthetic chemistry of nanomaterials and polyoxometalates.
Synthesis and Affinity Evaluation of a Small Library of Bidentate Cholera Toxin Ligands: Towards Nonhydrolyzable Ganglioside Mimics
Authors: Cheshev Pavel , Morelli Laura , Marchesi Marco , Podlipnik Črtomir , Bergström Maria , Bernardi Anna
Published: December 2009

A small library of nonhydrolyzable mimics of GM1 ganglioside, featuring galactose and sialic acid as pharmacophoric carbohydrate residues, was synthesized and tested. All compounds were synthesized from readily available precursors using high‐performance reactions, including click chemistry protocols, and avoiding O‐glycosidic bonds. Some of the most active molecules also feature a point of further derivatization that can be used for conjugation with polyvalent aglycons. Their affinity towards cholera toxin was assessed by weak affinity chromatography, which allowed a systematic evaluation and selection of the best candidates. Affinity could be enhanced up to one or two orders of magnitude over the affinity of the individual pharmacophoric sugar residues.
A Panchromatic Supramolecular Fullerene‐Based Donor–Acceptor Assembly Derived from a Peripherally Substituted Bodipy–Zinc Phthalocyanine Dyad
Authors: Rio Yannick , Seitz Wolfgang , Gouloumis Andreas , Vázquez Purificacion , Sessler Jonathan L. , Guldi Dirk M. , Torres Tomás
Published: December 2009

A panchromatic 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene –zinc phthalocyanine conjugate (Bodipy–ZnPc) 1 was synthesized starting from phthalocyanine aldehyde 4, via dipyrromethane 3 and dipyrromethene 2. Conjugate 1 represents the first example in which a Bodipy unit is tethered to the peripheral position of a phthalocyanine core. Electrochemical and optical measurements provided evidence for strong electronic interactions between the Bodipy and ZnPc constituents in the ground state of 1. When conjugate 1 is subjected to photoexcitation in the spectral region corresponding to the Bodipy absorption, the strong fluorescence characteristic of the latter subunit is effectively quenched (i.e., ≥97 %). Excitation spectral analysis confirmed that the photoexcited Bodipy and the tethered ZnPc subunits interact and that intraconjugate singlet energy transfer occurs with an efficiency of ca. 25 %. Treatment of conjugate 1 with N‐pyridylfulleropyrrolidine (8), an electron‐acceptor system containing a nitrogen ligand, gives rise to the novel electron donor–acceptor hybrid 1↔8 through ligation to the ZnPc center. Irradiation of the resulting supramolecular ensemble within the visible range leads to a charge‐separated Bodipy–ZnPc.+–C60.− radical‐ion‐pair state, through a sequence of excited‐state and charge transfers, characterized by a remarkably long lifetime of 39.9 ns in toluene.
Platinum Nanoparticles: The Crucial Role of Crystal Face and Colloid Stabilizer in the Diastereoselective Hydrogenation of Cinchonidine
Authors: Schmidt Erik , Kleist Wolfgang , Krumeich Frank , Mallat Tamas , Baiker Alfons
Published: December 2009

The preparation of stable metal nanoparticles requires a strong interaction between the (organic) stabilizer and the metal surface that might alter the catalytic properties. This behavior has been described as “poisoning” since the stabilizer normally decreases the catalytic activity due to site blocking. Here we show a striking influence of the stabilizer on the selectivity in the hydrogenation of cinchonidine (CD) over poly(acrylic acid) (PAA)‐stabilized Pt nanoparticles with well‐defined shape distributions. In the hydrogenation of the heteroaromatic ring of cinchonidine in toluene, the diastereomeric excess of the (S)‐hexahydrocinchonidine increased upon increasing Pt{111}/Pt{100} ratio, but this distinct shape selectivity was observed only after the oxidative removal of PAA at 473 K. The use of the as‐prepared nanoparticles inverted the major diastereomer to R, and this isomer was formed also in acetic acid. This striking change in the diastereoselectivity indicates that poly(acrylic acid), which remains on the Pt surface after preparation, interacts with CD during hydrogenation almost as strongly as the solvent acetic acid. The PAA stabilizer plays a dual role: it allows one to control the size and shape of the nanoparticles during their synthesis, and it affects the rate and diastereoselectivity of the hydrogenation of CD probably through a “surface‐localized acidification”.
Gold(I)‐Catalyzed Glycosylation with Glycosyl ortho‐Alkynylbenzoates as Donors: General Scope and Application in the Synthesis of a Cyclic Triterpene Saponin
Authors: Li Yao , Yang Xiaoyu , Liu Yunpeng , Zhu Cunsheng , Yang You , Yu Biao
Published: December 2009

Glycosyl ortho‐alkynylbenzoates have emerged as a new generation of donors for glycosidation under the catalysis of gold(I) complexes such as Ph3PAuOTf and Ph3PAuNTf2 (Tf=trifluoromethanesulfonate). A wide variety of these donors, including 2‐deoxy sugar and sialyl donors, are easily prepared and shelf stable. The glycosidic coupling yields with alcohols are generally excellent; even direct coupling with the poorly nucleophilic amides gives satisfactory yields. Moreover, excellent α‐selective glycosylation with a 2‐deoxy sugar donor and β‐selective sialylation have been realized. Application of the present glycosylation protocol in the efficient synthesis of a cyclic triterpene tetrasaccharide have further demonstrated the versatility and efficacy of this new method, in that a novel chemoselective glycosylation of the carboxylic acid and a new one‐pot sequential glycosylation sequence have been implemented.
Cobalt‐Mediated Radical Coupling (CMRC): An Unusual Route to Midchain‐Functionalized Symmetrical Macromolecules
Authors: Debuigne Antoine , Poli Rinaldo , De Winter Julien , Laurent Pascal , Gerbaux Pascal , Dubois Philippe , Wathelet Jean‐Paul , Jérôme Christine , Detrembleur Christophe
Published: December 2009

Cobalt‐mediated radical coupling (CMRC) is a straightforward approach to the synthesis of symmetrical macromolecules that relies on the addition of 1,3‐diene compounds onto polymer precursors preformed by cobalt‐mediated radical polymerization (CMRP). Mechanistic features that make this process so efficient for radical polymer coupling are reported here. The mechanism was established on the basis of NMR spectroscopy and MALDI‐MS analyses of the coupling product and corroborated by DFT calculations. A key feature of CMRC is the preferential insertion of two diene units in the middle of the chain of the coupling product mainly according to a trans‐1,4‐addition pathway. The large tolerance of CMRC towards the diene structure is demonstrated and the impact of this new coupling method on macromolecular engineering is discussed, especially for midchain functionalization of polymers. It is worth noting that the interest in CMRC goes beyond the field of polymer chemistry, since it constitutes a novel carbon–carbon bond formation method that could be applied to small organic molecules.
Multifunctional Magnetic Materials Obtained by Insertion of a Spin‐Crossover FeIII Complex into Bimetallic Oxalate‐Based Ferromagnets
Authors: Clemente‐León Miguel , Coronado Eugenio , López‐Jordà Maurici , Mínguez Espallargas Guillermo , Soriano‐Portillo Alejandra , Waerenborgh João C.
Published: December 2009

The syntheses, structures and magnetic properties of the compounds of formula [FeIII(sal2‐trien)][MnIICrIII(ox)3]⋅CH2Cl2 (1; H2sal2‐trien=N,N′‐disalicylidenetriethylenetetramine, ox=oxalate), [FeIII(sal2‐trien)][MnIICrIII(ox)3]⋅CH3OH (2), [InIII(sal2‐trien)][MnIICrIII(ox)3]⋅0.25 H2O ⋅0.25 CH3OH⋅0.25 CH3CN (3), and [InIII(sal2‐trien)][MnIICrIII(ox)3]⋅CH3NO2 ⋅0.5 H2O (4) are reported. The structure of 1 presents a 2D honeycomb anionic layer formed by MnII and CrIII ions linked through oxalate ligands and a cationic layer of [Fe(sal2‐trien)]+ complexes intercalated between the 2D oxalate network. The structures of 2, 3, and 4 present a 3D achiral anionic network formed by MnII and CrIII ions linked through oxalate ligands with [Fe(sal2‐trien)]+ or [In(sal2‐trien)]+ complexes and solvent molecules intercalated within the 3D oxalate network. The magnetic properties and Mössbauer spectroscopy of 1 and 2 indicate that these compounds undergo a long‐range ferromagnetic ordering at around 5 K and a spin crossover of the intercalated [Fe(sal2‐trien)]+ complexes above 130 K, which is complete in the case of 1. The magnetic properties of the compounds 3 and 4 confirm the ferromagnetic ordering of the bimetallic oxalate network.
Dynamic Kinetic Asymmetric Transformation (DYKAT) by Combined Amine‐ and Transition‐Metal‐Catalyzed Enantioselective Cycloisomerization
Authors: Zhao Gui‐Ling , Ullah Farman , Deiana Luca , Lin Shuangzheng , Zhang Qiong , Sun Junliang , Ibrahem Ismail , Dziedzic Pawel , Córdova Armando
Published: December 2009

The first examples of one‐pot highly chemo‐ and enantioselective dynamic kinetic asymmetric transformations (DYKATs) involving α,β‐unsaturated aldehydes and propargylated carbon acids are presented. These DYKATs, which proceed by a combination of catalytic iminium activation, enamine activation, and Pd0‐catalyzed enyne cycloisomerization, give access to functionalized cyclopentenes with up to 99 % eeand can be used for the generation of all‐carbon quaternary stereocenters.
Identification, SAR Studies, and X‐ray Co‐crystallographic Analysis of a Novel Furanopyrimidine Aurora Kinase A Inhibitor
Authors: Coumar Mohane Selvaraj , Tsai Ming‐Tsung , Chu Chang‐Ying , Uang Biing‐Jiun , Lin Wen‐Hsing , Chang Chun‐Yu , Chang Teng‐Yuan , Leou Jiun‐Shyang , Teng Chi‐Huang , Wu Jian‐Sung , Fang Ming‐Yu , Chen Chun‐Hwa , Hsu John T.‐A. , Wu Su‐Ying , Chao Yu‐Sheng , Hsieh Hsing‐Pang
Published: December 2009

Herein we reveal a simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in‐house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in‐house compound library collection prior to testing. Five new series of Aurora kinase inhibitors were identified through this strategy, with IC50 values ranging from ∼300 nM to ∼15 μM, by testing only 133 compounds from a database of ∼125 000 compounds. Structure–activity relationship studies and X‐ray co‐crystallographic analysis of the most potent compound, a furanopyrimidine derivative with an IC50 value of 309 nM toward Aurora kinase A, were carried out. The knowledge gained through these studies could help in the future design of potent Aurora kinase inhibitors.
Ovarian metastases from breast cancer
Authors: Bigorie Veronique , Morice Philippe , Duvillard Pierre , Antoine Martine , Cortez Annie , Flejou Jean François , Uzan Serge , Darai Emile , Barranger Emmanuel
Published: December 2009

BACKGROUND:

The objective of this study was to describe the characteristics and survival outcomes of patients with breast cancer who had ovarian metastases.

METHODS:

Data from 29 women who underwent surgery were reviewed retrospectively (from 1998 to 2007). Patient characteristics, tumor characteristics, and treatment data were collected. Pelvic extent of disease was documented using a system analogous to the International Federation of Gynecology and Obstetrics classification for ovarian cancer. Global survival, disease‐free intervals, and the distribution to other metastatic sites over time were studied. Outcomes were compared between the group who underwent macroscopic resection of lesions and the group who did not undergo resection.

RESULTS:

The data indicated a predominance of premenopausal and hormone receptor‐positive status and a greater prevalence of lobular infiltrating carcinoma, bilateral breast cancer, and predisposing genetic factors compared with the global population with breast cancer. Ovarian disease was diagnosed at a median of 5 years after breast cancer. Seventy‐five percent of patients were asymptomatic, and advanced‐stage pelvic extent or extra‐abdominal metastases were observed in 41.5% of patients. The median survival was 3 years, and the median follow‐up was 2 years. Survival improved significantly when optimal debulking surgery was performed.

CONCLUSIONS:

Breast cancers may be associated with ovarian metastases. The current results indicated that surgical resection tends to increase survival, which may be long; however, larger series would be needed to confirm other prognostic factors. The high rates of hormone receptor‐positive tumors and premenopausal patients led the authors to suggest that the surgical option should consist of at least bilateral oophorectomy, even when the contralateral ovary appears to be normal. Cancer 2010. © 2010 American Cancer Society.
Knowledge of hepatitis C virus screening in long‐term pediatric cancer survivors
Authors: Lansdale Meagan , Castellino Sharon , Marina Neyssa , Goodman Pamela , Hudson Melissa M. , Mertens Ann C. , Smith Stephanie M. , Leisenring Wendy , Robison Leslie L. , Oeffinger Kevin C.
Published: December 2009

BACKGROUND:

Pediatric cancer survivors who were treated before routine hepatitis C virus (HCV) screening of blood donors in 1992 have an elevated risk of transfusion‐acquired HCV.

METHODS:

To assess long‐term pediatric cancer survivors' knowledge of HCV testing and blood transfusion history, a questionnaire was administered to 9242 participants in the Childhood Cancer Survivor Study who are at risk for transfusion‐acquired HCV after cancer therapy from 1970 to 1986.

RESULTS:

More than 70% of survivors reported either no prior HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting prior testing. One half recalled having a treatment‐related blood transfusion; those who recalled a transfusion were more likely to report HCV testing (39%) than those who did not (18%) or were unsure (20%). In multivariate models, survivors who reported no prior HCV testing were more likely to be older (odds ratio [OR] per 5‐year increase, 1.1; 95% confidence interval [CI], 1.0‐1.1) and to report no care at a cancer center within the past 2 years (OR, 1.2; 95% CI, 1.0‐1.4), no cancer treatment summary (OR, 1.3; 95% CI, 1.2‐1.5), and no transfusions (OR, 2.6; 95% CI, 2.3‐3.0) or uncertainty about transfusions (OR, 2.2; 95% CI, 1.9‐2.6), and less likely to be racial/ethnic minorities (OR, 0.9; 95% CI, 0.8‐1.0) or survivors of acute myeloid leukemia (OR, 0.7; 95% CI, 0.5‐1.0).

CONCLUSIONS:

Many pediatric cancer survivors at risk for transfusion‐acquired HCV are unaware of their transfusion history and prior testing for HCV and would benefit from programs to increase HCV knowledge and screening. Cancer 2010. © 2010 American Cancer Society.
Correlation of pretransplant and early post‐transplant response assessment with outcomes after reduced‐intensity allogeneic hematopoietic stem cell transplantation for non‐Hodgkin's lymphoma
Authors: Bishop Michael R. , Dean Robert M. , Steinberg Seth M. , Odom Jeanne , Pollack Seth M. , Pavletic Steven Z. , Sportes Claude , Gress Ronald E. , Fowler Daniel H.
Published: December 2009

BACKGROUND:

Chemotherapy sensitivity, defined simply as at least a partial response to chemotherapy, is an important outcome predictor for non‐Hodgkin lymphoma (NHL) patients undergoing reduced‐intensity allogeneic hematopoietic stem cell transplantation (allo‐HCT). The authors hypothesized that further differentiation of chemotherapy sensitivity by specific response, complete remission (CR) versus partial remission (PR) versus stable disease (SD) versus progression of disease (PD), correlates with post‐transplant outcomes.

METHODS:

The impact of pretransplant and early (28 days) post‐transplant disease response on transplant outcomes was analyzed in 63 NHL patients treated with reduced‐intensity allo‐HCT.

RESULTS:

The 3‐year event‐free survival (EFS) and overall survival (OS) (median potential follow‐up after reduced‐intensity allo‐HCT = 58 months) for all patients was 37% and 47%, respectively. The 3‐year EFS based on pretransplant response was: CR = 50%; PR = 66%; SD = 18%; no patient with PD pretransplant reached 3‐year follow‐up. The 3‐year OS based on pretransplant response was: CR = 63%; PR = 69%; SD = 45%. The 3‐year EFS based on post‐transplant response was: CR = 57%; PR = 32%; SD = 33%; no patient with PD post‐transplant reached 3‐year follow‐up. The 3‐year OS based on post‐transplant response was: CR = 65%; PR = 43%; SD = 50%. In multivariate analyses, pretransplant response was the best predictor of EFS (P< .0001). Pretransplant response (P< .0001) and age (P= .0035) were jointly associated with OS.

CONCLUSIONS:

These data suggest that NHL patients with pretransplant SD, generally considered inappropriate candidates, may benefit from reduced‐intensity allo‐HCT, and patients with pretransplant PD should only receive this therapy in clinical trials. Cancer 2010. © 2010 American Cancer Society.
Altered balance of γ‐aminobutyic acidergic and glutamatergic afferent inputs in rostral ventrolateral medulla‐projecting neurons in the paraventricular nucleus of the hypothalamus of renovascular hypertensive rats
Authors: Biancardi Vinicia Campana , Campos Ruy Ribeiro , Stern Javier Eduardo
Published: December 2009

An imbalance of excitatory and inhibitory functions has been shown to contribute to numerous pathological disorders. Accumulating evidence supports the idea that a change in hypothalamic γ‐aminobutyic acid (GABA)‐ergic inhibitory and glutamatergic excitatory synaptic functions contributes to exacerbated neurohumoral drive in prevalent cardiovascular disorders, including hypertension. However, the precise underlying mechanisms and neuronal substrates are still not fully elucidated. In the present study, we combined quantitative immunohistochemistry with neuronal tract tracing to determine whether plastic remodeling of afferent GABAergic and glutamatergic inputs into identified RVLM‐projecting neurons of the hypothalamic paraventricular nucleus (PVN‐RVLM) contributes to an imbalanced excitatory/inhibitory function in renovascular hypertensive rats (RVH). Our results indicate that both GABAergic and glutamatergic innervation densities increased in oxytocin‐positive, PVN‐RVLM (OT‐PVN‐RVLM) neurons in RVH rats. Despite this concomitant increase, time‐dependent and compartment‐specific differences in the reorganization of these inputs resulted in an altered balance of excitatory/inhibitory inputs in somatic and dendritic compartments. A net predominance of excitatory over inhibitory inputs was found in OT‐PVN‐RVLM proximal dendrites. Our results indicate that, along with previously described changes in neurotransmitter release probability and postsynaptic receptor function, remodeling of GABAergic and glutamatergic afferent inputs contributes as an underlying mechanism to the altered excitatory/inhibitory balance in the PVN of hypertensive rats. J. Comp. Neurol. 518:567–585, 2010. © 2010 Wiley‐Liss, Inc.
The Temperature‐Dependent Hydrogen‐Bonding Signature of Lipids Monitored in the Far‐Infrared Domain
Authors: Hielscher Ruth , Hellwig Petra
Published: December 2009

Phospholipids are studied by means of Fourier transform infrared (FTIR) spectroscopy in the mid‐ and far‐infrared spectral ranges, thereby establishing the hydrogen‐bonding continuum as a function of the temperature. The well‐known mid‐infrared spectrum of the phospholipid layer clearly shows a temperature‐dependent phase transition. In the far‐infrared region (from 300 to 50 cm−1), an alternation of the interaction between the phospholipids and water molecules is found. The hydrogen‐bonding network ensemble and bound water molecules can be monitored in this spectral region. The lipid structure is found to strongly influence the intermolecular hydrogen‐bonding interplay. Thus, studies in the far‐infrared region provide significant information—at the molecular level—about the intermolecular hydrogen‐bonding signature of self‐assembled phospholipids.
The Relevance of the Collaborative Effect in Determining the Performances of Photorefractive Polymer Materials
Authors: Angelone Rocco , Ciardelli Francesco , Colligiani Arturo , Greco Francesco , Masi Paolo , Romano Annalisa , Ruggeri Giacomo
Published: December 2009

A derivative of 2‐methylindole, 3‐[2‐(4‐nitrophenyl)ethenyl]‐1‐allyl‐2‐methylindole, NPEMI‐A, is studied for its photoconductivity and photorefractivity behaviour. Its blends with the organic polymer poly‐(2,3‐dimethyl‐N‐vinylindole), PVDMI, are also investigated. Due to the expected and devised mutual solubility of the two components of the blends, it is possible to carry out measurements with the weight percent of the chromophore NPEMI‐A changing from zero to 100. Films were produced by a squeezing process between two ITO‐covered glass sheets. No opacity phenomena, that are so common for many other organic blends due to the segregation of the dissolved chromophore, are observed. The photorefractive optical gain Γ2 is obtained as a function of the chromophore content. Differential scanning calorimetry measurements (DSC) are also carried out to obtain the whole change of the glass transition temperature Tg as a function of the amount of chromophore contained in the blends. From the experimental trend of Tg a meaningful quantitative estimate of the value of the electrostatic interactions acting in the studied blends, is obtained. The importance of the value of Tg, and of the electrostatic interactions, in determining the extent of the photorefractivity is clearly evident. The results are compared for NPEMI‐A (Γ2=210 cm−1) and for NPEMI‐E (Γ2 ≈ 2000 cm−1) that has a N‐2‐ethylhexyl group instead of a N‐allyl group. The Pockels and Kerr contributions and—for the first time—a “collaborative effect” of the photorefractivity of NPEMI‐A are distinguished and quantitatively evaluated.