bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of Nearly Monodisperse Iron Oxide and Oxyhydroxide Nanocrystals
Authors: Liang X. , Wang X. , Zhuang J. , Chen Y. , Wang D. , Li Y. 
Published: August 2006

AbstractUniform magnetite, hematite, and goethite nanocrystals were prepared through an attractive method based on an oleic acid/alcohol/water system. By adjusting the synthetic parameters (base concentration, alcohol content, categories of alcohols, etc.), the controlled synthesis of uniform magnetite, hematite, and goethite nanocrystals can be easily achieved. Detailed investigations on the effect of the experimental parameters on the morphology of the final products and the phase transitions among the magnetite, hematite, and goethite phases were carried out. Finally, a method of doping other metal ions into magnetite was developed and the magnetic properties of magnetite doped with different metal elements were studied.
A pH‐Responsive Gating Membrane System with Pumping Effects for Improved Controlled Release
Authors: Qu J.‐B. , Chu L.‐Y. , Yang M. , Xie R. , Hu L. , Chen W.‐M. 
Published: August 2006

AbstractIn this study, we report on a novel composite membrane system for pH‐responsive controlled release, which is composed of a porous membrane with linear grafted, positively pH‐responsive polymeric gates acting as functional valves, and a crosslinked, negatively pH‐responsive hydrogel inside the reservoir working as a functional pumping element. The proposed system features a large responsive release rate that goes effectively beyond the limit of concentration‐driven diffusion due to the pumping effects of the negatively pH‐responsive hydrogel inside the reservoir. The pH‐responsive gating membranes were prepared by grafting poly(methacrylic acid) (PMAA) linear chains onto porous polyvinylidene fluoride (PVDF) membrane substrates using a plasma‐graft pore‐filling polymerization, and the crosslinked poly(N,N‐dimethylaminoethyl methacrylate) (PDM) hydrogels were synthesized by free radical polymerization. The volume phase‐transition characteristics of PMAA and PDM were opposite. The proposed system opens new doors for pH‐responsive “smart” or “intelligent” controlled‐release systems, which are highly attractive for drug‐delivery systems, chemical carriers, sensors, and so on.
On the use of detailed models in the MPC algorithm: The pressure‐swing distillation case
Authors: Fissore Davide , Pin Marco , Barresi Antonello A. 
Published: August 2006

AbstractA novel approach to the design of a model predictive control (MPC) algorithm for a complex plant (with energy integration and mass recycles) is given. Sensitivity analysis and steady‐state optimization are used to determine the manipulated variables that have the strongest influence on the objective function of the operation. This allows a reduction of the number of variables that are optimized on‐line, as well as the use of detailed, first‐principle–based models in the MPC algorithm, thus resulting in more reliable predictions. Moreover, the same algorithm can be used to control plants of different size, without the need of a new calibration of the parameters of the model. The application of this procedure to a pressure‐swing distillation unit is given as an example. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Intraskeletal variability in bone mass
Authors: Peck Joshua J. , Stout Sam D. 
Published: August 2006

AbstractFor methodological or other reasons, a variety of skeletal elements are analyzed and subsequently used as a basis for describing general bone loss and mass. However, bone loss and mass may not be uniform within and among skeletal elements of the same individual because of biomechanical factors. We test the hypothesis that a homogeneity in bone mass exists among skeletal elements of the same individual. Measures indicative of bone mass were calculated from the midshafts of six skeletal elements from the same individuals (N = 41). The extent of intraskeletal variability in bone mass (relative cortical area) was then examined for the entire sample, according to age, sex, and pathological status. The results of the analysis showed that all measures reflect a heterogeneity in bone mass (P ≤ 0.001). Specifically, differences were observed between the bones of the upper limb and those of the lower limb. Both sexes showed intraskeletal variability in bone mass, but the difference between the sexes is not significant (P = 0.509). When the sample is subdivided according to age, all groups show intraskeletal variability in bone mass, but the difference did not differ significantly among the groups (P = 0.217). However, significant differences in intraskeletal variability are observed between individuals below and above the age of 50. Pathological individuals show intraskeletal variability in bone mass, but the difference between the pathological and non‐pathological groups is not significant (P = 0.095). These results indicate that the bone mass of any particular skeletal element is intricately tethered to its specific mechanical loading environment. Am J Phys Anthropol, 2006. © 2006 Wiley‐Liss, Inc.
Ruthenium‐Catalyzed Oxidation of Alkenes, Alkynes, and Alcohols to Organic Acids with Aqueous Hydrogen Peroxide
Authors: Che Chi‐Ming , Yip Wing‐Ping , Yu Wing‐Yiu 
Published: August 2006

AbstractA protocol that adopts aqueous hydrogen peroxide as a terminal oxidant and [(Me3tacn)(CF3CO2)2RuIII(OH2)]CF3CO2 (1; Me3tacn=1,4,7‐trimethyl‐1,4,7‐triazacyclononane) as a catalyst for oxidation of alkenes, alkynes, and alcohols to organic acids in over 80 % yield is presented. For the oxidation of cyclohexene to adipic acid, the loading of 1 can be lowered to 0.1 mol %. On the one‐mole scale, the oxidation of cyclohexene, cyclooctene, and 1‐octanol with 1 mol % of 1 produced adipic acid (124 g, 85 % yield), suberic acid (158 g, 91 % yield), and 1‐octanoic acid (129 g, 90 % yield), respectively. The oxidative CC bond‐cleavage reaction proceeded through the formation of cis‐ and trans‐diol intermediates, which were further oxidized to carboxylic acids via CC bond cleavage.
Highly Enantiomerically Enriched Planar Chiral Naphthalene Tricarbonylchromium Complexes
Authors: Cumming Graham R. , Bernardinelli Gérald , Kündig E. Peter 
Published: August 2006

AbstractLithiation/electrophile trapping reactions were carried out with the highly enantiomerically enriched complex [Cr(5‐bromonaphthalene)(CO)3]. Electrophile quenching with ClPPh2, PhCHO, and (Me3SiO)2 afforded the enantiomerically enriched (>97 % ee) planar chiral 5‐substituted naphthalene complexes with PPh2, CH(Ph)OH, and OH substituents, respectively. Very mild Pd‐catalyzed Suzuki–Miyaura cross‐coupling reactions were developed and applied to the highly labile [Cr(5‐bromonaphthalene)(CO)3] to give nine new planar chiral aryl‐, heteroaryl‐, alkynyl‐, and alkenylnaphthalene chromium complexes with high enantiomeric purity. The efficient ambient‐temperature coupling reactions with borinates prepared in situ were also applied to a number of chlorobenzene complexes and to aryl and vinyl halides.
Confirmatory Seamless Phase II/III Clinical Trials with Hypotheses Selection at Interim: Applications and Practical Considerations
Authors: Schmidli Heinz , Bretz Frank , Racine Amy , Maurer Willi 
Published: August 2006

AbstractAdaptive seamless phase II/III designs combine a phase II and a phase III study into one single confirmatory clinical trial. Several examples of such designs are presented, where the primary endpoint is binary, time‐to‐event or continuous. The interim adaptations considered include the selection of treatments and the selection of hypotheses related to a pre‐specified subgroup of patients. Practical aspects concerning the planning and implementation of adaptive seamless confirmatory studies are also discussed. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An Overview of Statistical Approaches for Adaptive Designs and Design Modifications
Authors: Schäfer Helmut , Timmesfeld Nina , Müller Hans‐Helge 
Published: August 2006

AbstractWith adaptive design methods for clinical trials, design elements such as sample size or further interim sample sizes may be changed during the course of the trial depending on all previously collected data. The focus of the overview is on group sequential approaches where the types of adaptations need not be specified in advance. An overview of the different statistical approaches for adaptive design methods proposed in the literature is given, relations between these methods are described and some perspectives of application and for future research are discussed. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Opening the Adaptive Toolbox
Authors: Wittes Janet , Lachenbruch Peter A. 
Published: August 2006

AbstractThis is a discussion of the following three papers appearing in this special issue on adaptive designs: ‘A regulatory view on adaptive/flexible clinical trial design’ by H. M. James Hung, Robert T. O'Neill, Sue‐Jane Wang and John Lawrence; ‘Confirmatory clinical trials with an adaptive design’ by Armin Koch; and ‘FDA's critical path initiative: A perspective on contributions of biostatistics’ by Robert T. O'Neill. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Some Aspects of the Application of Internal Pilot Studies
Authors: Lachenbruch Peter A. , Wittes Janet 
Published: August 2006

AbstractThis is a discussion of the paper' Sample size recalculation in internal pilot study designs' by Tim Friede and Meinhard Kieser, appearing in this special issue on adaptive designs. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Methodological Developments vs. Regulatory Requirements
Authors: Bauer Peter 
Published: August 2006

AbstractThis is a discussion of the following three papers appearing in this special issue on adaptive designs: ‘FDA’s critical path initiative: A perspective on contributions of biostatistics' by Robert T. O'Neill, ‘A regulatory view on adaptive/flexible clinical trial design’ by H. M. James Hung, Robert T. O'Neill, Sue‐Jane Wang and John Lawrence; and ‘Confirmatory clinical trials with an adaptive design’ by Armin Koch. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Adaptive Designs from the Viewpoint of an Academic Biostatistician
Authors: Schäfer Helmut 
Published: August 2006

AbstractThis is a discussion of the following three papers appearing in this special issue on adaptive designs: ‘FDA's critical path initiative: A perspective on contributions of biostatistics’ by Robert T. O'Neill, ‘A regulatory view on adaptive/flexible clinical trial design’ by H. M. James Hung, Robert T. O'Neill, Sue‐Jane Wang and John Lawrence; and ‘Confirmatory clinical trials with an adaptive design’ by Armin Koch. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Consultant's Perspective on the Regulatory Hurdles to Adaptive Trials
Authors: Mehta Cyrus R. , Jemiai Yannis 
Published: August 2006

AbstractThis is a discussion of the following two papers appearing in this special issue on adaptive designs: ‘A regulatory view on adaptive/flexible clinical trial design’ by H. M. James Hung, Robert T. O'Neill, Sue‐Jane Wang and John Lawrence and ‘Confirmatory clinical trials with an adaptive design’ by Armin Koch. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Challenges in Implementing Adaptive Designs: Comments on the Viewpoints Expressed by Regulatory Statisticians
Authors: Gallo Paul , Maurer Willi 
Published: August 2006

AbstractThis is a discussion of the following three papers appearing in this special issue on adaptive designs: ‘FDA's critical path initiative: A perspective on contributions of biostatistics’ by Robert T. O'Neill; ‘A regulatory view on adaptive/flexible clinical trial design’ by H. M. James Hung, Robert T. O'Neill, Sue‐Jane Wang and John Lawrence; and ‘Confirmatory clinical trials with an adaptive design’ by Armin Koch. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mapping and partial characterization of proteases expressed by a CHO production cell line
Authors: Sandberg H. , Lütkemeyer D. , Kuprin S. , Wrangel M. , Almstedt A. , Persson P. , Ek V. , Mikaelsson M. 
Published: August 2006

AbstractThe proteolytic activities expressed by a Chinese hamster ovary (CHO) cell line in the cultivation supernatant during the production of recombinant factor VIII were mapped with a broad spectrum protease assay and a series of different types of protease inhibitors. The destabilizing effect on the product emanated from a metalloproteinase, which could be effectively blocked by chelating agents to lead to product stabilization. Amino acid sequences of the isolated metalloproteinase were found to have sequence homology with matrix metalloproteinases (MMPs) MMP3, MMP10, and MMP12. Several species with metalloproteinase activity were characterized and found to be related to each other. The results indicate that an MMP pro‐enzyme of ≥200 kDa was released from the CHO cells during the production phase. The enzyme expressed collagenase/gelatinase activity when activated. Due to autoproteolysis, a number of smaller, less specific MMPs were formed with the smallest form, a 19.4 kDa protein, being the most active. These results may be of particular relevance for other production processes using CHO cells for the expression of recombinant proteins. © 2006 Wiley Periodicals, Inc.
Derivation and characterization of cholesterol‐independent non‐GS NS0 cell lines for production of recombinant antibodies
Authors: Hartman Taymar E. , Sar Nalin , Genereux Kimberly , Barritt Diana S. , He Yimin , Burky John E. , Wesson Mark C. , Tso J. Yun , Tsurushita Naoya , Zhou Weichang , Sauer Paul W. 
Published: August 2006

AbstractPresented is an antibody production platform based on the fed‐batch culture of recombinant NS0‐derived cell lines. NS0 host cells, obtained from the European Collection of Cell Cultures (ECACC, Salisbury, UK, Part No. 85110503), were first adapted to grow in a protein‐free, cholesterol‐free medium. The resulting host cell line was designated NS0‐PFCF (protein‐free, cholesterol‐free). The five production cell lines presented here were generated using a common protocol consisting of transfection by electroporation and subcloning. The NS0‐PFCF host cell line was transfected using a single expression vector containing the Escherichia coli xanthine‐guanine phosphoribosyl transferase gene (gpt), and the antibody heavy and light chain genes driven by the CMV promoter. The five cell lines were chosen after one to three rounds of iterative subcloning, which resulted in a 19–64% increase in antibody productivity when four mother–daughter cell pairs were cultured in a fed‐batch bioreactor process. The production cell lines were genetically characterized to determine antibody gene integrity, nucleotide sequences, copy number, and the number of insertion sites in the NS0 cell genome. Genetic characterization data indicate that each of the five production cell lines has a single stably integrated copy of the antibody expression vector, and that the antibody genes are correctly expressed. Stability of antibody production was evaluated for three of the five cell lines by comparing the early stage seed bank with the Working Cell Bank (WCB). Antibody productivity was shown to be stable in two of three cell lines evaluated, while one of the cell lines exhibited a 20% drop in productivity after passaging for approximately 4 weeks. These five NS0‐derived production cell lines were successfully cultured to produce antibodies with acceptable product quality attributes in a standardized fed‐batch bioreactor process, consistently achieving an average specific productivity of 20–60 pg/cell‐day, and a volumetric productivity exceeding 120 mg/L‐day (Burky et al., 2006). In contrast to the commonly available NS0 host cell line, which requires serum and cholesterol for growth, and the commonly used expression vector system, which uses a proprietary glutamine synthetase selection marker (GS‐NS0), these NS0 cells are cholesterol‐independent, grow well in a protein‐free medium, use a non‐proprietary selection marker, and do not require gene amplification for productivity improvement. These characteristics are advantageous for use of this NS0 cell line platform for manufacturing therapeutic antibodies. Biotechnol. Bioeng. 2007;96: 294–306. © 2006 Wiley Periodicals, Inc.
Thermally induced gelable polymer networks for living cell encapsulation
Authors: Lu Hong‐Fang , Targonsky Elisha D. , Wheeler Michael B. , Cheng Yu‐Ling 
Published: August 2006

AbstractWe report the encapsulation of MIN6 cells, a pancreatic β‐cell line, using thermally induced gelable materials. This strategy uses aqueous solvent and mild temperatures during encapsulation, thereby minimizing adverse effects on cell function and viability. Using a 2:1 mixture of PNIPAAm‐PEG‐PNIPAAm tri‐block copolymer and PNIPAAm homopolymer that exhibit reversible sol‐to‐gel transition at ∼30°C, gels were formed that exhibit mechanical integrity, and are stable in H2O, PBS and complete DMEM with negligible mass loss at 37°C for 60 days. MTT assays showed undetectable cytotoxicity of the polymers towards MIN6 cells. A simple microencapsulation process was developed using vertical co‐extrusion and a 37°C capsule collection bath containing a paraffin layer above DMEM. Spherical capsules with diameters ranging from 500 to 900 µm were formed. SEM images of freeze‐dried capsules with PBS as the core solution showed homogenous gel capsule membranes. Confocal microscopy revealed that the encapsulated cells tended to form small aggregates over 5 days, and staining for live and dead cells showed high viability post‐encapsulation. A static glucose challenge with day‐5 cultured microencapsulated cells exhibited glucose‐dependent insulin secretion comparable to controls of free MIN6 cells grown in monolayers. These results demonstrate the potential use of these thermo‐responsive polymers as cell encapsulation membranes. Biotechnol. Bioeng. 2007;96: 146–155. © 2006 Wiley Periodicals, Inc.
Salt stress effects on the central and carnitine metabolisms of Escherichia coli
Authors: Cánovas M. , Bernal V. , Sevilla A. , Iborra J.L. 
Published: August 2006

AbstractThe aim was to understand how interaction of the central carbon and the secondary carnitine metabolisms is affected under salt stress and its effect on the production of L‐carnitine by Escherichia coli. The biotransformation of crotonobetaine into L‐carnitine by resting cells of E. coli O44 K74 was improved by salt stress, a yield of nearly twofold that for the control being obtained with 0.5 M NaCl. Crotonobetaine and the L‐carnitine formed acted as an osmoprotectant during cell growth and biotransformation in the presence of NaCl. The enzyme activities involved in the biotransformation process (crotonobetaine hydration reaction and crotonobetaine reduction reaction), in the synthesis of acetyl‐CoA/acetate (pyruvate dehydrogenase, acetyl‐CoA synthetase [ACS] and ATP/acetate phosphotransferase) and in the distribution of metabolites for the tricarboxylic acid cycle (isocitrate dehydrogenase [ICDH]) and glyoxylate shunt (isocitrate lyase [ICL]) were followed in batch with resting cells both in the presence and absence of NaCl and in perturbation experiments performed on growing cells in a high density cell recycle membrane reactor. Further, the levels of carnitine, crotonobetaine, γ‐butyrobetaine and ATP and the NADH/NAD+ ratio were measured in order to know how the metabolic state was modified and coenzyme pools redistributed as a result of NaCl's effect on the energy content of the cell. The results provided the first experimental evidence of the important role played by salt stress during resting and growing cell biotransformation (0.5 M NaCl increased the L‐carnitine production in nearly 85%), and the need for high levels of ATP to maintain metabolite transport and biotransformation. Moreover, the main metabolic pathways and carbon flow operating during cell biotransformation was that controlled by the ICDH/ICL ratio, which decreased from 8.0 to 2.5, and the phosphotransferase/ACS ratio, which increased from 2.1 to 5.2, after a NaCl pulse fivefold the steady‐state level. Resting E. coli cells were seen to be made up of heterogeneous populations consisting of several types of subpopulation (intact, depolarized, and permeabilized cells) differing in viability and metabolic activity as biotransformation run‐time and the NaCl concentration increased. The results are discussed in relation with the general stress response of E. coli, which alters the NADH/NAD+ ratio, ATP content, and central carbon enzyme activities. Biotechnol. Bioeng. 2007;96:722–737. © 2006 Wiley Periodicals, Inc.
Successful transfection of hepatoma cells after encapsulation of plasmid DNA into negatively charged liposomes
Authors: Zhang Hong‐Wei , Zhang Ling , Sun Xun , Zhang Zhi‐Rong 
Published: August 2006

AbstractThe application of conventional cationic liposomes/DNA complexes in gene transfer was hampered due to their large size, instability, and limited transfection site in vivo. In this report, we described a dialysis‐based method and produced small, stable, and negatively charged DNA‐containing liposomes composed of low content of cationic lipid and high content of fusogenic lipid. The liposomes were relatively spherical with a condensed core inside, and exhibited small size with narrow particle size distribution. The encapsulation efficiency of the liposomes was 42.53 ± 2.29%. They were stable and showed enough protective ability to plasmid DNA from degradation after incubation with different amounts of DNase. Twenty‐fold higher transfection efficiency for the liposomes was achieved when compared with that of naked plasmid DNA and no toxicities to hepatocellular carcinoma cells were observed. Our results indicate that the negatively charged DNA‐containing liposomes can facilitate gene transfer in cultured cells, and may alleviate the drawbacks of the conventional cationic liposomes/DNA complexes for gene delivery in vivo. Biotechnol. Bioeng. 2007;96: 118–124. © 2006 Wiley Periodicals, Inc.
Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long‐term to Zidovudine
Authors: Divi Rao L. , Haverkos Kathryn J. , Humsi Juliette A. , Shockley Marie E. , Thamire Chandrasekhar , Nagashima Kunio , Olivero Ofelia A. , Poirier Miriam C. 
Published: August 2006

AbstractLong‐term use of antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs) as therapy for human immunodeficiency virus‐1 (HIV‐1) infection is limited by mitochondrial toxicity. Here we document mitochondrial pathology during the long‐term culture of human HeLa cells in the presence or absence of the NRTI Zidovudine® (AZT, 800 μM) for up to 77‐passages (p), with samples taken at early (p5–p11), middle (p36 and p37), and late (p70–p77) passages. Samples were analyzed for changes in mitochondrial morphology, mitochondrial (mt)DNA quantity, nuclear and mitochondrial gene expression, and mitochondrial membrane potential. Mitochondria showed abnormal proliferation at p5 and abnormal morphology ≥p36. mtDNA quantity was increased at p5 and p11, and 65% depleted at p71. Hierarchical clustering of nuclear gene expression, examined at p37 by the NCI cDNA microarray in AZT‐exposed cells, showed down‐regulation of 13 out of 16 lipid‐metabolizing genes, and up‐regulation of most oxidative phosphorylation (OXPHOS) genes. OXPHOS genes encoded by mtDNA, examined at p5, p36, and p75 using the Mitochondrial Gene Mini Array, revealed up‐regulation of genes coding for polypeptides of NADH dehydrogenase, ATP synthase, and cytochrome c oxidase. Mitochondrial membrane potential, monitored by JC1 staining, was elevated at p10 and p32, and essentially completely absent at p71. The data show that during chronic exposure of HeLa cells to AZT, a compensatory response was induced at the earlier passages (p5–p37), and by p71 there was widespread mitochondrial morphological damage, severe mtDNA depletion, and a substantial loss of mitochondrial membrane potential. Environ. Mol. Mutagen., 2006. Published 2006 Wiley‐Liss, Inc.