bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiasthmatic Agents
Authors: Erb Klaus J. , Martyres Domnic H. , Seither Peter
Published: January 2010

The article contains sections titled:1.Introduction2.Bronchodilators (Relievers)2.1.Adrenoceptor Agonists2.1.1.Aminocatechol Derivatives2.1.2.Resorcinol Derivatives2.1.3.Saligenin Derivatives2.1.4.Further Arylalkylamines2.2.Xanthine Derivatives2.3.Anticholinergic Drugs3.Anti‐Inflammatory Drugs or Controllers3.1.Glucocorticosteroids3.2.Antileukotrienes3.3.Cromolyns3.4.Anti‐IgE Antibodies3.5.Allergen‐Specific Immunotherapy4.Fixed Dose Combination Therapies4.1.Fixed Dose Combinations of Adrenoceptor Agonists and Glucocorticosteroids4.2.Fixed Dose Combinations of Adrenoceptor Agonists and Anticholinergic Drugs4.3.Fixed Dose Combinations of Adrenoceptor Agonists and Cromolyns4.4.Fixed Dose Combinations of Xanthines5.Newer Concepts in Asthma Therapy
Bubble Columns
Authors: Deen N.G. , Mudde R.F. , Kuipers J.A.M. , Zehner Peter , Kraume Matthias
Published: January 2010

The article contains sections titled:1.Introduction2.Bubble Columns2.1.Design and Applications2.2.Gas Distribution2.3.Flow Regimes2.4.Bubble Size2.5.Bubble Rise Velocity2.6.Axial Dispersion2.7.Gas Holdup2.8.Specific Interfacial Area2.9.Mass Transfer2.10.Heat Transfer2.11.Fluid Dynamics3.Airlift Loop Reactors3.1.Design and Applications3.2.Mixing Behavior and Fluid Dynamics3.3.Gas Holdup3.4.Mass Transfer and Mixing3.5.Heat Transfer3.6.Computational Fluid Dynamics
Membrane Reactors
Authors: Drioli Enrico , Fontananova Enrica
Published: January 2010

Membrane reactors (MRs) are systems in which a membrane separation process is combined with a chemical (catalytic) reaction. Because there are different ways to combine a catalyst with a membrane in order to have a synergic effect on the entire process, there are numerous possible categorizations of these systems. Some useful classifications are presented to highlight the advantages and still‐existing limitations of MRs in comparison with traditional reactors. Classification can be based on the role of the membrane in the catalytic process (catalytically active or providing only a separation function), the type of transport through the membrane (extractor‐, distributor‐, and contactor‐type MRs), the natures of the membrane material (organic or inorganic) and catalyst (artificial or biological). Applications of MRs in high‐temperature reactions using inorganic membranes and in low‐temperature MRs using polymer membranes are presented, as well as large‐scale applications in membrane bioreactors for wastewater treatment.1.Introduction2.Extractor‐, Distributor‐, and Contactor‐Type Membrane Reactors3.Organic and Inorganic Membrane Reactors4.Biocatalytic Membrane Reactors5.Catalytically Active and Catalytically Inert Membranes
Adhesives, 2. Applications
Authors: Onusseit Hermann , Wefringhaus Rainer , Dreezen Gunther , Kneafsey Brendan , Wichelhaus Jürgen , Bachon Thomas , Becker Kevin , Chen Chunfu , Dausmann Dieter , Gillitzer Tatiana , Gossen Ralf , Gupta Shashi , Holloway Matthew , Iida Kazutoshi , Jacobine Anthony F. , Kopannia Siegfried , Lammerschop Olaf , Lu Daniel , Mayer Bernd , Meckel‐Jonas Claudia , Picker Stefan , Pröbster Manfred , Ruyters Michel , Sattler Hans‐Peter , Schöttmer Bernhard , Windhövel Udo
Published: January 2010

The article contains sections titled:1.Paper and Packaging Industry1.1.Graphic Products1.1.1.Bookbinding1.1.1.1.Perfect Binding (Unsewn Binding) of Books1.1.1.2.Book Manufacture1.1.2.Fold Gluing1.2.Adhesives for Packaging and Packaging Materials1.2.1.Manufacture of Corrugated Board1.2.2.Lamination of Paper and Board1.2.3.Folder Gluer1.2.4.Folding Cartons1.2.5.Flexible Packages1.2.6.Bags, Sacks, and Pouches1.2.7.Adhesive Coating of Paper and Board1.2.8.Adhesives for Automatic Packaging Machines1.2.9.Reclosure Systems for Liquid Packaging Boards1.2.10.Membrane Bonding1.2.11.Pallet Securing1.3.Envelopes and Advertising Mail1.4.Cigarette Manufacture1.5.Labeling1.6.Nonwovens Hygiene Industry1.7.Hygienic Tissue Papers2.Gluing of Wood and Wooden Materials3.Footwear Adhesives4.Bonding of Plastics5.Bonding of Elastomers5.1.Postvulcanization Bonding of Rubber5.2.Vulcanization Bonding of Rubber6.Bonding of Metals7.Adhesives for Wallcoverings8.Flooring Adhesives9.Building Construction Adhesives10.Adhesives for Bonding Textile Fabrics11.Flocking Adhesives12.Adhesives for Bonding Glass13.Adhesives in Automobile Manufacture14.Adhesives in Aircraft Construction15.Adhesives and Sealants in Electronics15.1.Introduction15.2.Conductive Adhesives15.3.Coating and Protection Products15.4.Surface Mounting Adhesives15.5.Adhesives for Flat‐Panel Display Manufacture16.Medical Adhesives17.Household Adhesives and Do‐It‐Yourself Products17.1.Household Adhesives17.1.1.Adhesive Rollers (Paper Adhesives in Cassette Form)17.2.Do‐It‐Yourself Products18.Applications of Anaerobic Adhesives18.1.Introduction18.2.Main Applications Types18.2.1.Threadlockers18.2.2.Threadsealants18.2.3.Chemical Gaskets18.2.4.Retaining Compounds18.2.5.Porous‐Metal Sealing (PMS)18.3.Limitations for Anaerobic Adhesive Applications18.4.Formulation Ingredients and Chemistry18.4.1.Methacrylate Esters18.4.2.Curatives18.4.3.Initiation or Polymerization Accelerators–Promoters18.4.4.Rheological Additives18.4.5.Performance Additives19.Adhesives in Transportation Industry19.1.Introduction19.2.Sandwich Elements19.3.Commercial Vehicles/Buses19.4.Recreational Vehicles19.5.Railway19.6.Shipbuilding19.7.Refrigerated Containers19.8.Future Trends20.Adhesives in Low‐Pressure Molding for Electronic Components
Pharmaceutical Coatings
Authors: Warnke Gernot
Published: January 2010

The article contains sections titled:

1.

Introduction

2.

Coating Substrates

3.

Types of Film Coatings

3.1.

Aesthetic Coatings

3.2.

Functional Coatings

3.3.

Coating Components

3.3.1.

Polymers

3.3.2.

Plasticizers

3.3.3.

Fillers

3.3.4.

Pigments

3.3.5.

Solvents

3.3.6.

Other Ingredients

4.

Processes and Equipment

4.1.

Wetting

4.2.

Drying

4.3.

Blending

5.

Troubleshooting

6.

Testing

6.1.

Tests on the Coating Formulation

6.2.

Tests on Cast Films

6.3.

Tests on the Finished Product
Long‐term mortality and renal outcome in a cohort of 100 patients with Lupus Nephritis
Authors: Faurschou Mikkel , Dreyer Lene , Kamper Anne‐Lise , Starklint Henrik , Jacobsen Søren
Published: January 2010

Objective

To evaluate the long‐term mortality and renal outcome in a cohort of Danish patients with lupus nephritis (LN) and to identify outcome predictors among findings registered at the time of the first renal biopsy.

Methods

The cohort consisted of 100 patients diagnosed with LN (World Health Organization classes I–VI) between 1971 and 1995 and followed for a median duration of 14.7 years (range 0.01–36.9 years). Standardized mortality ratios (SMRs) were calculated on the basis of national age‐, sex‐, and calendar‐year period–specific death rates.

Results

Thirty‐seven deaths occurred in the cohort, corresponding to an overall SMR of 6.8 (95% confidence interval [95% CI] 4.9–9.4). Excess mortality was observed throughout followup. The SMR estimates were 9.0 (95% CI 4.7–17.1), 6.2 (95% CI 4.0–9.5), and 6.6 (95% CI 3.1–13.8) for patients diagnosed during the calendar‐year periods 1971–1979, 1980–1989, and 1990–1995, respectively. The cumulative renal survival after 5, 10, and 20 years of followup was 87%, 83%, and 73%, respectively. The risk of end‐stage renal disease (ESRD) did not decrease significantly across calendar‐year periods. Systolic blood pressure ≥180 mm Hg, focal segmental nephritis, and advanced sclerosing nephritis were identified as baseline predictors of death in multivariate regression analyses, while systolic blood pressure ≥180 mm Hg, serum creatinine level ≥140 μmoles/liter, and diagnostic delay predicted progression to ESRD.

Conclusion

LN is associated with excess long‐term mortality, and patients may progress to ESRD even after prolonged followup. Our analyses indicate that focal segmental histopathology at disease onset constitutes an important risk factor for death among LN patients. Moreover, our data underscore the importance of early intervention, blood pressure control, and long‐term followup in LN.
Feeding ecology of a group of buffy‐headed marmosets (Callithrix flaviceps): fungi as a preferred resource
Authors: Hilário Renato R. , Ferrari Stephen F.
Published: January 2010

Mycophagy is a relatively rare behavior in primates and has only been recorded in five callitrichid species. Here, we present data on the feeding ecology of a free‐ranging group ofCallithrix flaviceps, which was studied in the Augusto Ruschi Biological Reserve, Southeastern Brazil, in 2008. In contrast with other marmosets, which are typically gummivorous, the study group was predominantly mycophagous–insectivorous, with fungi corresponding to 64.8% of total feeding records, and gum (6.1%) and fruit (3.3%) together providing only a minor part of the diet. Prey corresponded to 25.8% of the group's diet. The fungi (Mycocitrusspp.) consumed by the marmosets were found attached to the stems ofMerostachysbamboo. As the animal component of the group's diet was similar to that recorded in studies of other marmosets, we propose that fungi were exploited primarily as a substitute for plant material, in particular exudates. This highly mycophagous diet may be determined by two principal factors: (1) the abundance of fungi within the study area, and (2) the avoidance of bark gouging, for whichC. flavicepsmay be less specialized than most other marmosets. These conclusions are supported by comparisons with other marmoset groups, which indicate an ecological specialization for mycophagy inC. flaviceps, and that the species will resort to gummivory in habitats where fungi are scarce. Am. J. Primatol. 72:515–521, 2010. © 2010 Wiley‐Liss, Inc.
Protection against anti–citrullinated protein antibody–positive rheumatoid arthritis is predominantly associated with HLA–DRB1*1301: A meta‐analysis of HLA–DRB1 associations with anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis in four European populations
Authors: van der Woude Diane , Lie Benedicte A. , Lundström Emeli , Balsa Alejandro , Feitsma Anouk L. , Houwing‐Duistermaat Jeanine J. , Verduijn Willem , Nordang Gry B. N. , Alfredsson Lars , Klareskog Lars , Pascual‐Salcedo Dora , Gonzalez‐Gay Miguel A. , Lopez‐Nevot Miguel A. , Valero Fernando , Roep Bart O. , Huizinga Tom W. J. , Kvien Tore K. , Martín Javier , Padyukov Leonid , de Vries René R. P. , Toes René E. M.
Published: January 2010

Objective

The protective effect of HLA–DRB1 alleles on the development of rheumatoid arthritis (RA) is poorly understood. The aim of this study was to perform a meta‐analysis of 4 European populations to investigate which HLA–DRB1 alleles are associated with protection in anti–citrullinated protein antibody (ACPA)–positive RA and ACPA‐negative RA.

Methods

Data for >2,800 patients and >3,000 control subjects for whom information on HLA–DRB1 typing and ACPA status was available were collected from 4 European countries: Norway, Sweden, The Netherlands, and Spain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the different HLA–DRB1 alleles were analyzed in a combined meta‐analysis focused on protective alleles and classifications. The analysis of ACPA‐positive RA was stratified for the shared epitope (SE) alleles, to correct for skewing due to this association.

Results

In ACPA‐positive RA, the only alleles that conveyed protection after stratification for SE were HLA–DRB1*13 alleles (OR 0.54 [95% CI 0.38–0.77]). The protective effect of the allele classifications based on the DERAA and D70 sequences was no longer present after exclusion of DRB1*13 (for D70, OR 0.97 [95% CI 0.75–1.25]), indicating that DRB1*13, rather than the DERAA or D70 sequence as such, is associated with protection. Among the DRB1*13 alleles, only DRB1*1301 was associated with protection (OR 0.24 [95% CI 0.09–0.59]). Protection appeared to follow a north‐to‐south gradient, with the strongest association in northern European countries. In ACPA‐negative RA, there were no robust associations with HLA–DRB1 alleles.

Conclusion

Our data do not support any of the classifications of protective alleles and indicate that protection against ACPA‐positive RA is predominantly associated with HLA–DRB1*1301.
Expanding the phenotypic spectrum of lupus erythematosus in Aicardi‐Goutières syndrome
Authors: Ramantani Georgia , Kohlhase Jürgen , Hertzberg Christoph , Innes A. Micheil , Engel Kerstin , Hunger Susan , Borozdin Wiktor , Mah Jean K. , Ungerath Kristina , Walkenhorst Hartmut , Richardt Hans‐Helmut , Buckard Johannes , Bevot Andrea , Siegel Corinna , von Stülpnagel Celina , Ikonomidou Chrysanthy , Thomas Kara , Proud Virginia , Niemann Frank , Wieczorek Dagmar , Häusler Martin , Niggemann Pascal , Baltaci Volkan , Conrad Karsten , Lebon Pierre , Lee‐Kirsch Min Ae
Published: January 2010

Objective

Aicardi‐Goutières syndrome (AGS) is an early‐onset encephalopathy resembling congenital viral infection that is characterized by basal ganglia calcifications, loss of white matter, cerebrospinal fluid (CSF) lymphocytosis, and elevated interferon‐α levels in the CSF. Studies have shown that AGS is an autosomal‐recessive disease linked to mutations in 5 genes, encoding the 3′‐repair DNA exonuclease 1 (TREX1), the 3 subunits of ribonuclease H2 (RNASEH2A–C), and sterile alpha motif domain and HD domain–containing protein 1 (SAMHD1). In this study we further characterized the phenotypic spectrum of this disease.

Methods

Clinical and laboratory data were obtained from 26 patients fulfilling the clinical diagnostic criteria for AGS. Genomic DNA was screened for mutations in all 5 AGS genes by direct sequencing, and sera were analyzed for autoantibodies.

Results

In 20 patients with AGS, 20 mutations, 12 of which were novel, were identified in all 5 AGS genes. Clinical and laboratory investigations revealed a high prevalence of features (some not previously described in patients with AGS) that are commonly seen in patients with systemic lupus erythematosus (SLE), such as thrombocytopenia, leukocytopenia, antinuclear antibodies, erythematous lesions, oral ulcers, and arthritis, which were observed in 12 (60%) of 20 patients with AGS. Moreover, the coexistence of AGS and SLE, was for the first time, demonstrated in 2 patients with molecularly proven AGS.

Conclusion

These findings expand the phenotypic spectrum of lupus erythematosus in AGS and provide further insight into its disease mechanisms by showing that activation of the innate immune system as a result of inherited defects in nucleic acid metabolism could lead to systemic autoimmunity.
Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice
Authors: Ramanujam Meera , Bethunaickan Ramalingam , Huang Weiqing , Tao Haiou , Madaio Michael P. , Davidson Anne
Published: January 2010

Objective

To determine whether BAFF or combined BAFF/APRIL blockade is effective in a mouse model of systemic lupus erythematosus (SLE) nephritis characterized by rapidly progressive glomerulosclerosis.

Methods

NZM2410 mice at early and late stages of SLE nephritis were treated with a short course of BAFF‐R‐Ig or TACI‐Ig fusion protein. Proteinuria and serologic profile were evaluated every 2 weeks. Immunohistochemical, flow cytometric, and enzyme‐linked immunospot analyses of the spleen, kidney, and bone marrow were performed after 8 weeks and after 33 weeks.

Results

A short course of selective blockade of BAFF alone was sufficient to prevent and treat SLE nephritis in NZM2410 mice, despite the formation of pathogenic autoantibodies. Decreases in spleen size and B cell depletion persisted for more than 33 weeks after treatment and resulted in secondary decreases in CD4 memory T cell formation and activation of splenic and peripheral monocytes. Immune complex deposition in the kidneys was dissociated from renal damage and from activation of renal endothelial and resident dendritic cells.

Conclusion

Selective blockade of BAFF alone, which resulted in B cell depletion and splenic collapse, was sufficient to prevent and treat the disease in this model of noninflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.
Strategies to enhance cell growth and achieve high‐level oil production of a Chlorella vulgaris isolate
Authors: Chen Chun‐Yen , Yeh Kuei‐Ling , Su Huei‐Meei , Lo Yung‐Chung , Chen Wen‐Ming , Chang Jo‐Shu
Published: January 2010

The autotrophic growth of an oil‐rich indigenous microalgal isolate, identified as Chlorella vulgaris CC, was promoted by using engineering strategies to obtain the microalgal oil for biodiesel synthesis. Illumination with a light/dark cycle of 14/10 (i.e., 14 h light‐on and 10 h light‐off) resulted in a high overall oil production rate (voil) of 9.78 mg/L/day and a high electricity conversion efficiency (Ec) of 23.7 mg cell/kw h. When using a NaHCO3 concentration of 1,500 mg/L as carbon source, the voil and Ec were maximal at 100 mg/L/day and 128 mg/kw h, respectively. A Monod type model was used to describe the microalgal growth kinetics with an estimated maximum specific growth rate (μmax) of 0.605 day−1 and a half saturation coefficient (Ks) of 124.9 mg/L. An optimal nitrogen source (KNO3) concentration of 625 mg/L could further enhance the microalgal biomass and oil production, leading to a nearly 6.19 fold increase in voil value. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Rationally engineered biotransformation of p‐nitrophenol
Authors: Mattozzi Matthew de la Peña , Keasling Jay D.
Published: January 2010

An operon encoding enzymes responsible for degradation of the EPA priority contaminant para‐nitrophenol (PNP) from Pseudomonas sp. ENV2030 contains more genes than would appear to be necessary to mineralize PNP. To determine some necessary genes for PNP degradation, the genes encoding the proposed enzymes in the degradation pathway (pnpADEC) were assembled into a broad‐host‐range, BioBricks‐compatible vector under the control of a constitutive promoter. These were introduced into Escherichia coli DH10b and two Pseudomonas putida strains, one with a knockout of the aromatic transport TtgB and the parent with the native transporter. The engineered strains were assayed for PNP removal. E. coli DH10b harboring several versions of the refactored pathway was able to remove PNP from the medium up to a concentration of 0.2 mM; above which PNP was toxic to E. coli. A strain of P. putida harboring the PNP pathway genes was capable of removing PNP from the medium up to 0.5 mM. When P. putida harboring the native PNP degradation cluster was exposed to PNP, pnpADEC were induced, and the resulting production of β‐ketoadipate from PNP induced expression of its chromosomal degradation pathway (pcaIJF). In contrast, pnpADEC were expressed constitutively from the refactored constructs because none of the regulatory genes found in the native PNP degradation cluster were included. Although P. putida harboring the refactored construct was incapable of growing exclusively on PNP as a carbon source, evidence that the engineered pathway was functional was demonstrated by the induced expression of chromosomal pcaIJF. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Paracoccus denitrificans for the effluent recycling during continuous denitrification of liquid food
Authors: Tippkötter Nils , Roikaew Wipa , Ulber Roland , Hoffmann Alexander , Denzler Hans‐Jörg , Buchholz Heinrich
Published: January 2010

Nitrate is an undesirable component of several foods. A typical case of contamination with high nitrate contents is whey concentrate, containing nitrate in concentrations up to 25 l. The microbiological removal of nitrate by Paracoccus denitrificans under formation of harmless nitrogen in combination with a cell retention reactor is described here. Focus lies on the resource‐conserving design of a microbal denitrification process. Two methods are compared. The application of polyvinyl alcohol‐immobilized cells, which can be applied several times in whey feed, is compared with the implementation of a two step denitrification system. First, the whey concentrate's nitrate is removed by ion exchange and subsequently the eluent regenerated by microorganisms under their retention by crossflow filtration. Nitrite and nitrate concentrations were determined by reflectometric color measurement with a commercially available Reflectoquant® device. Correction factors for these media had to be determined. During the pilot development, bioreactors from 4 to 250 mg·L−1 and crossflow units with membrane areas from 0.02 to 0.80 m2 were examined. Based on the results of the pilot plants, a scaling for the exemplary process of denitrifying 1,000 tons per day is discussed. © 2010 American Institute of Chemical Engineers Biotechnol. Prog. 2010
Cellular level models as tools for cytokine design
Authors: Radhakrishnan Mala L. , Tidor Bruce
Published: January 2010

Cytokines and growth factors are critical regulators that connect intracellular and extracellular environments through binding to specific cell‐surface receptors. They regulate a wide variety of immunological, growth, and inflammatory response processes. The overall signal initiated by a population of cytokine molecules over long time periods is controlled by the subtle interplay of binding, signaling, and trafficking kinetics. Building on the work of others, we abstract a simple kinetic model that captures relevant features from cytokine systems as well as related growth factor systems. We explore a large range of potential biochemical behaviors, through systematic examination of the model's parameter space. Different rates for the same reaction topology lead to a dramatic range of biochemical network properties and outcomes. Evolution might productively explore varied and different portions of parameter space to create beneficial behaviors, and effective human therapeutic intervention might be achieved through altering network kinetic properties. Quantitative analysis of the results reveals the basis for tensions among a number of different network characteristics. For example, strong binding of cytokine to receptor can increase short‐term receptor activation and signal initiation but decrease long‐term signaling due to internalization and degradation. Further analysis reveals the role of specific biochemical processes in modulating such tensions. For instance, the kinetics of cytokine binding and receptor activation modulate whether ligand–receptor dissociation can generally occur before signal initiation or receptor internalization. Beyond analysis, the same models and model behaviors provide an important basis for the design of more potent cytokine therapeutics by providing insight into how binding kinetics affect ligand potency. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Alternating current electric field effects on neural stem cell viability and differentiation
Authors: Matos Marvi A. , Cicerone Marcus T.
Published: January 2010

Methods utilizing stem cells hold tremendous promise for tissue engineering applications; however, many issues must be worked out before these therapies can be routinely applied. Utilization of external cues for preimplantation expansion and differentiation offers a potentially viable approach to the use of stem cells in tissue engineering. The studies reported here focus on the response of murine neural stem cells encapsulated in alginate hydrogel beads to alternating current electric fields. Cell viability and differentiation was studied as a function of electric field magnitude and frequency. We applied fields of frequency (0.1–10) Hz, and found a marked peak in neural stem cell viability under oscillatory electric fields with a frequency of 1 Hz. We also found an enhanced propensity for astrocyte differentiation over neuronal differentiation in the 1 Hz cultures, as compared to the other field frequencies we studied. Published 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Optimization of cultivation conditions in spin tubes for Chinese hamster ovary cells producing erythropoietin and the comparison of glycosylation patterns in different cultivation vessels
Authors: Strnad Jure , Brinc Matjaž , Spudić Vatroslav , Jelnikar Nadja , Mirnik Lidija , Čarman Barbara , Kravanja Zdravko
Published: January 2010

This article describes the optimization of cultivation factor settings, that is the shaking rate and working volume in 50 mL spin tubes for a Chinese hamster ovary cell line expressing recombinant human α‐erythropoietin, using a response D‐optimal surface method. The main objectives of the research were, firstly, to determine a setting in which the product titer and product quality attributes in spin tubes are equivalent to those in 250 mL shake flasks in a seven day batch and, secondly, to find a setting in which the product titer is maximal. The model for product titer prediction as a function of shaking rate and working volume in the defined design space was successfully applied to the optimization of cultivation conditions in spin tubes for the tested cell line. Subsequently, validation experiments were carried out simultaneously in spin tubes, shake flasks and bench scale bioreactors to compare cell culture performance parameters such as growth, productivity and product quality attributes in the form of isoform profiles and glycan antennarity structures. The results of the experiments showed that similar cell culture performance and product quality could be achieved in spin tubes when compared to shake flasks. Additionally, bioreactor titers could be reproduced in spin tubes at high shaking rates and low working volumes, but with differing product quality. Cultivation at lower shaking rates in spin tubes and shake flasks produced a glycoprotein with a product quality slightly comparable to that from bioreactors, but with titers being only two thirds. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Recombinant murine growth hormone from E. coli inclusion bodies: Expression, high‐pressure solubilization and refolding, and characterization of activity and structure
Authors: Fradkin Amber Haynes , Boand Carl S. , Eisenberg Stephen P. , Rosendahl Mary S. , Randolph Theodore W.
Published: January 2010

We expressed recombinant murine growth hormone (rmGH) in E. coli as a cost‐effective way to produce large quantities (gram scale) of the protein for use in murine studies of immunogenicity to therapeutic proteins. High hydrostatic pressure was used to achieve high solubility and high refolding yields of rmGH protein produced in E. coli inclusion bodies. A two‐step column purification protocol was used to produce 99% pure monomeric rmGH. Secondary and tertiary structures of purified rmGH were investigated using circular dichroism and 2D‐UV spectroscopy. The purified rmGH produced was found to be biologically active in hypophysectomized rats. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Solvent‐Induced Structural Transition of Self‐Assembled Dipeptide: From Organogels to Microcrystals
Authors: Zhu Pengli , Yan Xuehai , Su Ying , Yang Yang , Li Junbai
Published: January 2010

Organogels that are self‐assembled from simple peptide molecules are an interesting class of nano‐ and mesoscale soft matter with simplicity and functionality. Investigating the precise roles of the organic solvents and their effects on stabilization of the formed organogel is an important topic for the development of low‐molecular‐weight gelators. We report the structural transition of an organogel self‐assembled from a single dipeptide building block, diphenylalanine (L‐Phe‐L‐Phe, FF), in toluene into a flower‐like microcrystal merely by introducing ethanol as a co‐solvent; this provides deeper insights into the phase transition between mesostable gels and thermodynamically stable microcrystals. Multiple characterization techniques were used to reveal the transitions. The results indicate that there are different molecular‐packing modes formed in the gels and in the microcrystals. Further studies show that the co‐solvent, ethanol, which has a higher polarity than toluene, might be involved in the formation of hydrogen bonds during molecular self‐assembly of the dipeptide in mixed solvents, thus leading to the transition of organogels into microcrystals. The structural transformation modulated by the co‐solvent might have a potential implication in controllable molecular self‐assembly.
Mechanism of the Asymmetric Autocatalytic Soai Reaction Studied by Density Functional Theory
Authors: Schiaffino Luca , Ercolani Gianfranco
Published: January 2010

The mechanism of the Soai reaction has been thoroughly investigated at the M05‐2X/6‐31G(d) level of theory, by considering ten energetically distinct paths. The study indicates the fully enantioselective catalytic cycle of the homochiral dimers to be the dominant mechanism. Two other catalytic cycles are shown to both be important for correct understanding of the Soai reaction. These are the catalytic cycle of the heterochiral dimer and the non‐enantioselective catalytic cycle of the homochiral dimers. The former has been proved to be not really competitive with the principal cycle, as required for the Soai reaction to manifest chiral amplification, whereas the latter, which is only slightly competitive with the principal one, nicely explains the experimental enantioselectivity observed in the reaction of 2‐methylpyrimidine‐5‐carbaldehyde. The study has also evidenced the inadequacy of the B3LYP functional for mechanistic investigations of the Soai reaction.
Dipolar Compounds Containing Fluorene and a Heteroaromatic Ring as the Conjugating Bridge for High‐Performance Dye‐Sensitized Solar Cells
Authors: Chen Chih‐Hsin , Hsu Ying‐Chan , Chou Hsien‐Hsin , Thomas K. R. Justin , Lin Jiann T. , Hsu Chao‐Ping
Published: January 2010

A novel series of dipolar organic dyes containing diarylamine as the electron donor, 2‐cyanoacrylic acid as the electron acceptor, and fluorene and a heteroaromatic ring as the conjugating bridge have been developed and characterized. These metal‐free dyes exhibited very high molar extinction coefficients in the electronic absorption spectra and have been successfully fabricated as efficient nanocrystalline TiO2 dye‐sensitized solar cells (DSSCs). The solar‐energy‐to‐electricity conversion efficiencies of DSSCs ranged from 4.92 to 6.88 %, which reached 68–96 % of a standard device of N719 fabricated and measured under the same conditions. With a TiO2 film thickness of 6 μm, DSSCs based on these dyes had photocurrents surpassing that of the N719‐based device. DFT computation results on these dyes also provide detailed structural information in connection with their high cell performance.
A phase 2 pilot trial of low‐dose, continuous infusion, or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma
Authors: Bhatt Rupal S. , Merchan Jaime , Parker Robert , Wu Hua‐Kang , Zhang Liang , Seery Virginia , Heymach John V. , Atkins Michael B. , McDermott David , Sukhatme Vikas P.
Published: January 2010

BACKGROUND:

Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX‐2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM.

METHODS:

Patients received paclitaxel 10 mg/m2 for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6‐week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study.

RESULTS:

Twenty patients were enrolled. Twelve of 20 patients (60%) had received ≥2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment‐related grade 3/4 toxicities were limited to catheter‐related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43‐151 days), and the median overall survival was 212 days (95% confidence interval, 147‐811 days).

CONCLUSIONS:

Low‐dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010. © 2010 American Cancer Society.
Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy
Authors: Auer Rebecca C. , White Rebekah R. , Kemeny Nancy E. , Schwartz Lawrence H. , Shia Jinru , Blumgart Leslie H. , DeMatteo Ronald P. , Fong Yuman , Jarnagin William R. , D'Angelica Michael I.
Published: January 2010

BACKGROUND:

During chemotherapy, some colorectal liver metastases (LMs) disappear on serial imaging. This disappearance may represent a complete response (CR) or a reduction in the sensitivity of imaging during chemotherapy. The objective of the current study was to determine the fate of disappearing LMs (DLMs) and the factors that predict a true CR.

METHODS:

Between 2000 and 2003, 435 patients who were evaluated by hepatobiliary surgeons received chemotherapy before they were considered for resection. Inclusion criteria were <12 LMs before chemotherapy, at least 1 DLM on a computed tomography (CT) scan, and either surgical resection or 1 year of clinical follow‐up after the disappearance of LMs. A true CR was defined as either a pathologic CR (no tumor detected in the resection specimen) or a durable clinical CR (did not reappear on follow‐up imaging). Clinical and pathologic factors were analyzed to identify those associated with a true CR.

RESULTS:

During chemotherapy, 39 patients (9%) had a total of 118 DLMs on follow‐up CT scans. Sixty‐eight DLMs were resected, and 50 were followed clinically. Overall, 75 DLMs (64%) were true CRs, including 44 pathologic CRs and 31 durable clinical CRs. On multivariate analysis, the use of hepatic arterial infusion (HAI) chemotherapy (odds ratio [OR], 6.2; P = .02), the inability to observe the DLM on a magnetic resonance image (OR, 4.7; P = .005), and normalization of serum carcinoembryonic antigen levels (OR, 4.6; P = .006) were associated independently with a true CR.

CONCLUSIONS:

Approximately 66% of DLMs represented a true CR according to assessment by resection or radiologic follow‐up. Predictive factors may help to stratify patients who are likely to harbor residual disease. Cancer 2010. © 2010 American Cancer Society.
Native American breast cancer survivors' physical conditions and quality of life
Authors: Burhansstipanov Linda , Krebs Linda U. , Seals Brenda F. , Bradley Alice A. , Kaur Judith S. , Iron Pamela , Dignan Mark B. , Thiel Carol , Gamito Eduard
Published: January 2010

BACKGROUND:

Based on Survivors' Guidance, an interactive, Web‐based, culturally relevant Native American cancer survivorship program, Native American Cancer Education for Survivors (NACES), was developed. The focus of the program is to improve quality of life (QOL) for Native American breast cancer survivors.

METHODS:

NACES is a community‐driven research and education project, based on the Social Cognitive Theoretical Model. Participants complete a QOL survey that includes physical, psychosocial, spiritual, and social components. This publication focuses on the physical component of the survey collected by trained Native American patient advocates, and compares physical conditions among Native American breast cancer survivors who were diagnosed within 1 year, those diagnosed between 1 and 4 years, and those who are long‐term survivors (diagnosed ≥5 years ago).

RESULTS:

For the first time, survivorship issues are reported specifically for Native American breast cancer patients (n = 266). Selected access issues document situations that contribute to disparities. Comorbidities such as high blood pressure and arthritis are common in the survivors, with more than a third having diabetes, in addition to breast cancer. Numerous side effects from cancer treatments are experienced by these survivors.

CONCLUSIONS:

These data describe what Native American breast cancer patients are experiencing based on self‐reported information. Clearly there is need for much more work and long‐term tracking of Native American patients to begin to document if or how the severity of physical symptoms lessens over time and if their experiences are significantly different from non‐Native Americans. Cancer 2010. © 2010 American Cancer Society.
Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase
Authors: Kantarjian Hagop M. , Cortes Jorge , La Rosée Paul , Hochhaus Andreas
Published: January 2010

Identification of BCR‐ABL as the defining leukemogenic event in chronic myelogenous leukemia (CML) revolutionized the treatment of the disease. Imatinib, a potent BCR‐ABL inhibitor, is the standard of care for the first‐line treatment of patients with chronic‐phase CML because of its high long‐term response rates and favorable tolerability profile compared with previous standard therapies. However, resistance to imatinib develops in 2% to 4% of patients annually. For patients with acquired cytogenetic resistance to standard‐dose imatinib (400 mg daily), imatinib dose escalation (600‐800 mg daily) is an excellent first option for managing patients and achieving cytogenetic responses. However, for patients with primary resistance to imatinib, hematologic disease recurrence, or emergent BCR‐ABL kinase domain mutations, imatinib dose escalation may not be sufficient to control the disease. For these patients, the potent second‐generation tyrosine kinase inhibitors dasatinib and nilotinib are available. Both agents provide effective therapeutic options for patients with imatinib resistance or intolerance. For the current overview, the authors reviewed the data supporting the use of both dasatinib and nilotinib in imatinib‐resistant or imatinib‐intolerant patients, and they have highlighted the future of CML therapy. Overall, the article is intended to offer physicians a comprehensive review of the current literature and to provide data supporting various treatment options for patients with CML throughout the course of imatinib therapy and beyond. Cancer 2010. © 2010 American Cancer Society.
Pharyngoesophageal reconstruction with the anterolateral thigh flap after total laryngopharyngectomy
Authors: Yu Peirong , Hanasono Matthew M. , Skoracki Roman J. , Baumann Donald P. , Lewin Jan S. , Weber Randal S. , Robb Geoffrey L.
Published: January 2010

BACKGROUND:

Pharyngoesophageal defects traditionally have been reconstructed using a jejunal or radial forearm flap. In 2002, the authors began using the anterolateral thigh flap for pharyngoesophageal reconstruction, and it has become our preferred method. The purpose of this study was to analyze the clinical and functional outcomes achieved using this technique.

METHODS:

The medical records of 91 male and 23 female patients who underwent pharyngoesophageal reconstruction using an anterolateral thigh flap were retrospectively reviewed. Outcomes analyzed included length of hospital and intensive care unit stay, fistula and anastomotic stricture formation and other complications, swallowing and tracheoesophageal speech function, and survival. Most patients had primary (27%) or recurrent (42%) squamous cell carcinoma. Before reconstruction, 71% of patients had undergone surgery, radiotherapy, or both. There were 67 circumferential and 47 near‐circumferential defects.

RESULTS:

Mean intensive care unit stay was 1.9 ± 2.2 days, and mean hospital stay was 9.0 ± 4.7 days. Two patients experienced total flap loss, and 1 patient had partial flap necrosis. Pharyngocutaneous fistulas and strictures occurred in 9% and 6% of patients, respectively. Ninety‐one percent of patients tolerated an oral diet without the need for tube feeding. Tracheoesophageal puncture was performed for speech rehabilitation in 51 patients. Eight‐one percent of patients with a secondary tracheoesophageal puncture achieved fluent speech versus 41% of patients with a primary tracheoesophageal puncture.

CONCLUSIONS:

This series demonstrates that excellent clinical and functional outcomes, with minimal donor site morbidity and quick recovery, are possible with pharyngoesophageal reconstruction using an anterolateral thigh flap. Cancer 2010. © 2010 American Cancer Society.
Differential distribution of tight junction proteins suggests a role for tanycytes in blood‐hypothalamus barrier regulation in the adult mouse brain
Authors: Mullier Amandine , Bouret Sebastien G. , Prevot Vincent , Dehouck Bénédicte
Published: January 2010

The median eminence is one of the seven so‐called circumventricular organs. It is located in the basal hypothalamus, ventral to the third ventricle and adjacent to the arcuate nucleus. This structure characteristically contains a rich capillary plexus and features a fenestrated endothelium, making it a direct target of blood‐borne molecules. The median eminence also contains highly specialized ependymal cells called tanycytes, which line the floor of the third ventricle. It has been hypothesized that one of the functions of these cells is to create a barrier that prevents substances in the portal capillary spaces from entering the brain. In this paper, we report on our use of immunohistochemistry to study the expression of tight junction proteins in the cells that compose the median eminence in adult mice. Our results indicate that tanycytes of the median eminence express occludin, ZO‐1, and claudin 1 and 5, but not claudin 3. Remarkably, these molecules are organized as a continuous belt around the cell bodies of the tanycytes that line the ventral part of the third ventricle. In contrast, the tanycytes at the periphery of the arcuate nucleus do not express claudin 1 and instead exhibit a disorganized expression pattern of occludin, ZO‐1, and claudin 5. Consistent with these observations, permeability studies using peripheral or central injections of Evans blue dye show that only the tanycytes of the median eminence are joined at their apices by functional tight junctions, whereas tanycytes located at the level of the arcuate nucleus form a permeable layer. In conclusion, this study reveals a unique expression pattern of tight junction proteins in hypothalamic tanycytes, which yields new insights into their barrier properties. J. Comp. Neurol. 518:943–962, 2010. © 2009 Wiley‐Liss, Inc.
Structural, optical, and electrical properties of electron beam evaporated CdSe thin films
Authors: Syed Basheer Ahamed M. G. , Balu A. R. , Nagarethinam V. S. , Thayumanavan A. , Murali K. R. , Sanjeeviraja C. , Jayachandran M.
Published: January 2010

CdSe films have been deposited on glass substrates at different substrate temperatures between room temperature and 300 °C. The films exhibited hexagonal structure with preferential orientation in the (002) direction. The crystallinity improved and the grain size increased with temperature. Band gap values are found decreasing from about 1.92 eV to 1.77 eV with increase of the substrate temperature. It is observed that the resistivity decreases continuously with temperature. Laser Raman studies show the presence of 2 LO and 3 LO peaks at 416 cm‐1 and 625 cm‐1respectively. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
1‐Substituted Cyclopentylamines from Nitriles and Tetramethylenebismagnesium Dibromide in the Presence of Ti(OiPr)4
Authors: Tomashenko Olesya A. , Rudenko Andrei E. , Sokolov Viktor V. , Tomashevskiy Alexander A. , de Meijere Armin
Published: January 2010

Various 1‐substituted cyclopentylamines (25 examples, 10–89 % yield) have been prepared according to a one‐pot procedure by the addition of tetramethylenebismagnesium dibromide in the presence of Ti(OiPr)4 to aliphatic, aromatic and heteroaromatic nitriles, respectively.
Silica spheres coated with C18‐modified gold nanoparticles for capillary LC and pressurized CEC separations
Authors: Qu Qishu , Peng Shengwei , Mangelings Debby , Hu Xiaoya , Yan Chao
Published: January 2010

Nonporous monodispersed silica spheres of 1.3 μm were coated with gold nanoparticles (AuNPs) and subsequently coated with n‐octadecanethiol. By transmission electron microscopy analysis, the average diameter of the AuNPs on the silica spheres was determined to be 12 nm. The chromatographic and electrochromatographic properties of self‐assembled n‐octadecanethiol AuNP‐coated silica microspheres (C18‐AuNPs‐SiO2) were investigated using a group of nonpolar PAHs. The stationary phase appears to display a characteristic reversed‐phase behavior. Higher separation efficiency and shorter separation times were obtained using pressurized CEC (pCEC) compared with capillary LC (CLC). A maximum column efficiency of about 2.5×105 plates per meter and less than 18 min separation time for benzene were obtained in pCEC while only 66 507 plates per meter and an analysis time of nearly 100 min were observed in CLC mode. A chemical stability test of the C18‐AuNPs‐SiO2 stationary phase under extremely high and low pH conditions demonstrated that it is stable at pH 12 and 1 for at least 60 h. The results confirm that C18‐AuNPs‐SiO2 possesses a high rigidity to withstand high packing pressures and can be used as a good stationary phase for CLC and pCEC.
Study on steady‐state kinetics of nucleotide analogues incorporation by non‐gel CE
Authors: Li Wujie , Cao Mou , Pei Lu , Ling Xiaomei , Li Bingchao , Yang Zhenjun
Published: January 2010

A method for studying steady‐state kinetics of nucleotide analogues incorporation into DNA strand by non‐gel CE (NGCE) with LIF was developed. Nucleoside analogue is a kind of antiviral agent used to inhibit viral replication in infected cells, especially HIV. Steady‐state parameter Km for nucleotide analogues is determined to imply the relationship between nucleoside analogues and the enzyme in the DNA chain elongation and predict the antiviral efficacy in vivo. Samples were prepared by single nucleotide incorporation assays catalyzed by Taq DNA polymerase at 58°C and HIV reverse transcriptase (RT) at 37°C, and then were separated using NGCE under optimized conditions: 25 mmol/L Tris‐boric‐EDTA buffer (pH 8.0) with 7 mmol/L urea in the presence of 20% w/v PEG 35000 at 30°C and −20 kV. Km(dTTP), Km(d4TTP) and Km(AZTTP) were measured by NGCE for the first time and their values for Taq DNA polymerase were 0.29±0.04, 32.1±3.3 and 74.5±6.6 μmol/L, respectively. For HIV RT, the values were 0.15±0.05, 0.31±0.03 and 0.17±0.03 μmol/L, respectively. The trend of data for HIV RT measured by NGCE was consistent with that measured by PAGE. The reported method by NGCE for the Km determination was powerful, sensitive and fast, and required less amounts of reagents compared with PAGE. It be employed as a reliable alternative method and further applied in other relative studies of nucleoside analogue substrates and DNA polymerases or RTs.