bluuebunny/crossref_metadata_2025_split huggingface dataset:
From preclinical to human – prediction of oral absorption and drug–drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach in an industrial setting: a workflow by using case example
Authors: Sinha Vikash Kumar , Snoeys Jan , Osselaer Nancy Van , Peer Achiel Van , Mackie Claire , Heald Donald 
Published: March 2012

ABSTRACTPurposeA case example is presented in which the physiologically based modeling approach has been used to model the absorption of a lipophilic BCS Class II compound predominantly metabolized by CYP3A4, and to assess the interplay of absorption related parameters with the drug–drug interaction (DDI) potential.MethodsThe PBPK model was built in the rat using Gastroplus® to study the absorption characteristics of the compound. Subsequently relevant model parameters were used to predict the non‐linear human PK observed during first‐in‐human study after optimizing the absorption model for colonic absorption, bile micelle solubilization and unbound fraction in gut enterocytes (fugut) using SIMCYP® simulator. The model fitted absorption parameters were then used to assess the drug–drug interaction (DDI) potential of the test compound when administered along with multiple doses of a potent CYP 3A4 inhibitor, ketoconazole. The impact of fugut in the extent of DDI was assessed using parameter sensitivity analysis.Results and ConclusionsAfter optimizing the preclinical model and taking into consideration bile micelle solubilization and colonic absorption, the non‐linear pharmacokinetics of the test compound was satisfactorily predicted in man. Sensitivity analysis performed with the absorption parameter fugut indicated that it could be an important parameter in predicting oral absorption. In addition, DDI simulations using SIMCYP® suggest that Cmax and AUC ratios may also be sensitive to the fugut input in the model. Since fugut cannot be measured experimentally, sensitivity analysis may help in assessing the importance of fugut in human PK and DDI prediction using SIMCYP®. Copyright © 2012 John Wiley & Sons, Ltd.
Using storage organelles for the accumulation and encapsulation of recombinant proteins
Authors: Khan Imran , Twyman Richard M. , Arcalis Elsa , Stoger Eva 
Published: March 2012

AbstractPlants have been used to produce many diverse and valuable recombinant proteins, including subunit vaccines, antibodies and antibody fragments, hormones, blood products, cytokines, and enzymes. Different plant species and platforms have been explored as production hosts, each with unique properties in terms of the gene transfer method, production time, environmental containment, scalability, downstream processing strategy, protein folding and accumulation, and overall costs. Seed‐based systems have many advantages because they exploit the natural storage properties of seeds, which facilitate batch processing and distribution. Seeds possess specialized storage organelles that may be used to accumulate recombinant proteins, offering stability both in planta and after harvest in the final preparation/formulation. The post‐harvest stabilizing effect of seeds allows recombinant subunit vaccines and antibodies to be delivered via the mucosal route because they are better able to withstand this harsh microenvironment when protected by the plant matrix. Native storage organelles such as starch granules and protein bodies offer this protective effect, but protein storage organelles can also be induced ectopically in vegetative tissues. In this paper, we discuss the technical capabilities of storage organelle‐based expression platforms and their potential applications.
Effect of light intensity on algal biomass accumulation and biodiesel production for mixotrophic strains Chlorella kessleri and Chlorella protothecoide cultivated in highly concentrated municipal wastewater
Authors: Li Yecong , Zhou Wenguang , Hu Bing , Min Min , Chen Paul , Ruan Roger R. 
Published: March 2012

AbstractIn this research, the effect of light intensity on biomass accumulation, wastewater nutrient removal through algae cultivation, and biodiesel productivity was investigated with algae species Chlorella kessleri and Chlorella protothecoide. The light intensities studied were 0, 15, 30, 60, 120, and 200 µmol m−2 s−1. The results showed that light intensity had profound impact on tested responses for both strains, and the dependence of these responses on light intensity varied with different algae strains. For C. kessleri, the optimum light intensity was 120 µmol m−2 S−1 for all responses except for COD removal. For C. protothecoide, the optimum light intensity was 30 µmol m−2 S−1. The major components of the biodiesel produced from algae biomass were 16‐C and 18‐C FAME, and the highest biodiesel contents were 24.19% and 19.48% of dried biomass for C. kessleri and C. protothecoide, respectively. Both species were capable of wastewater nutrients removal under all lighting conditions with high removal efficiencies. Biotechnol. Bioeng. 2012;109: 2222–2229. © 2012 Wiley Periodicals, Inc.
Self‐cycling operation increases productivity of recombinant protein in Escherichia coli
Authors: Storms Zachary J. , Brown Tobin , Sauvageau Dominic , Cooper David G. 
Published: March 2012

AbstractSelf‐cycling fermentation (SCF), a cyclical, semi‐continuous process that induces cell synchrony, was incorporated into a recombinant protein production scheme. Escherichia coli CY15050, a lac− mutant lysogenized with temperature‐sensitive phage λ modified to over‐express β‐galactosidase, was used as a model system. The production scheme was divided into two de‐coupled stages. The host cells were cultured under SCF operation in the first stage before being brought to a second stage where protein production was induced. In the first stage, the host strain demonstrated a stable cycling pattern immediately following the first cycle. This reproducible pattern was maintained over the course of the experiments and a significant degree of cell synchrony was obtained. By growing cells using SCF, productivity increased 50% and production time decreased by 40% compared to a batch culture under similar conditions. In addition, synchronized cultures induced from the end of a SCF cycle displayed shorter lysis times and a more complete culture‐wide lysis than unsynchronized cultures. Finally, protein synthesis was influenced by the time at which the lytic phase was induced in the cell life cycle. For example, induction of a synchronized culture immediately prior to cell division resulted in the maximum protein productivity, suggesting protein production can be optimized with respect to the cell life cycle using SCF. Biotechnol. Bioeng. 2012;109: 2262–2270. © 2012 Wiley Periodicals, Inc.
What if Web site editorial content and ads are in two different languages? A study of bilingual consumers' online information processing
Authors: Li Cong , Kalyanaraman Sriram 
Published: March 2012

ABSTRACTThis study examined banner ads' communication effects when they were written in the same or different language from the editorial content of a Web site. A total of 60 bilingual consumers who spoke both Chinese (as their first language) and English (as their second language) participated in an experiment, in which they viewed a designated news story Web site. The editorial content of the Web site and the banner ads on it were written in either Chinese or English. It was found that the participants considered the Chinese Web sites to be more readable. However, they generated higher recalls and purchase intentions for the ads on the English Web sites. Moreover, they revealed more favorable attitudes toward the brands when the ads were written in English than in Chinese. Copyright © 2012 John Wiley & Sons, Ltd.
A Model for the Phosphorus Dynamics of VPO Catalysts during the Selective Oxidation of n‐Butane to Maleic Anhydride in a Tubular Reactor
Authors: Diedenhoven Jelka , Reitzmann Andreas , Mestl Gerhard , Turek Thomas 
Published: March 2012

AbstractA model for the phosphorus dynamics in vanadium‐phosphorus oxide (VPO) catalysts for the oxidation of n‐butane to maleic anhydride was developed. According to the model, reversible sorption processes determine the phosphorus content of the catalyst. Simulations reveal that several phenomena can be successfully described. If no phosphorus is added to the reactant feed, the catalytic activity increases until runaway occurs. With addition of a proper amount of phosphorus, the loss can be compensated while excessive phosphorus addition results in complete catalyst deactivation. Adjusting the model parameters to experimental data may result in a model that can be used to optimize the performance of maleic anhydride reactors.
MgCl2/Et3N Base System as a New Catalyst for the Synthesis of α‐Hydroxyphosphonate
Authors: Tajbakhsh Mahmood , Khaksar Samad , Tafazoli Zahra , Bekhradnia Ahmadreza 
Published: March 2012

AbstractAn efficient and simple synthesis of α‐hydroxyphosphonates via reaction of aldehydes and ketones with dimethylphosphite in the presence of MgCl2/Et3N base system is reported. The use of readily available and easy to handle reagent MgCl2/Et3N makes this method simple, convenient, and practical.
Ground State Structures, Electronic and Magnetic Properties of ScnFe (n=2–10) Clusters
Authors: Yao Jiangang , Xu Bin , Wang Yuanxu 
Published: March 2012

AbstractThe authors predict that the magnetic moment of the scandium clusters can not be efficiently enhanced with the encapsulation of Fe atom, which is different from previous works with Fe atom doped in Bn, Sin, and Gen clusters. It was found that starting from n=6, the growth patterns of the ground state structures of the ScnFe clusters are dominated by the octahedron structures with Fe atom falling into the center of the host framework. The calculated results manifest that doping of the Fe atom contributes to strengthening the stabilities of the scandium framework. Maximum peaks are observed for clusters of n=3, 6 and 8 on the size dependence of the second‐order energy differences, implying that these clusters possess relatively higher stability. The HOMO‐LUMO gap of the ScnFe clusters exhibits an oscillational odd‐even character with the local peaks of n=4, 6 and 8. Especially, there is the largest oscillation of the gap with n=4 and 5. Additionally, the doped Fe atom exhibits the antiferromagnetic alignment at n=4, 5, 7 and 9. Also, the quench of the magnetic moments as n=6, 8 and 10 may be ascribed to the model of close‐shell electrons.
Pd‐NHC‐Catalyzed Direct Arylation of 1,4‐Disubstituted 1,2,3‐Triazoles with Aryl Halides
Authors: He Tao , Wang Min , Li Pinhua , Wang Lei 
Published: March 2012

AbstractA highly efficient method for the synthesis of unsymmetrical multi‐substituted 1,2,3‐triazoles via a direct Pd‐NHC system catalyzed C(5)‐arylation of 1,4‐disubstituted triazoles, which are readily accessible via "click" chemistry has been developed. It is important to note that CH bond functionalizations of 1,2,3‐triazoles with a variety of differently substituted aryl iodides and bromides as electrophiles can be conveniently achieved through this catalytic system at significantly milder reaction temperatures of 100°C under air.
Identification of the Most Stable Sc2C80 Isomers: Structure, Electronic Property, and Molecular Spectra Investigations
Authors: Wu Jingyi , Wang Taishan , Shu Chunying , Lü Xin , Wang Chunru 
Published: March 2012

AbstractA systematic density functional theory investigation has been carried out to explore the possible structures of Sc2C80 at the BMK/6‐31G(d) level. The results clearly show that Sc2@C80‐Ih, Sc2@C80‐D5h, and Sc2C2@C78‐C2v can be identified as three isomers of Sc2C80 metallofullerene with the lowest energy. Frontier molecular orbital analysis indicates that the two Sc2@C80 isomers have a charge state as (Sc3+)2@C806−and the Sc2C2@C78 has a charge state of (Sc3+)2C22−@C784−. Moreover, the metal‐cage covalent interactions have been studied to reveal the dynamics of endohedral moiety. The vertical electron affinity, vertical ionization potential, infrared spectra and 13C nuclear magnetic resonance spectra have been also computed to further disclose the molecular structures and properties.
Sodium Acetate‐catalyzed Regiospecific and High Stereoselective Aminobromination of β,β‐Dicyanostyrene Derivatives with NBS as Nitrogen/Bromine Source
Authors: Li Wenli , Chen Zhanguo , Zhou Jimei , Hu Junli , Xia Wei 
Published: March 2012

AbstractAn easy and efficient method for the aminobromination of β,β‐dicyanostyrene derivatives with NBS as the aminobrominating reagent in CH3CN catalyzed by NaOAc (10 mol%) is developed. This protocol provides convenient process to convert β,β‐dicyanostyrene derivatives into the vicinal haloamines with full regiospecificity and high stereoselectivety in the ice‐water bath in air. The reaction is high efficient in yielding the corresponding aminobrominated products in excellent yields (up to 95%) under these conditions. The outcome indicated that the reaction has an electrophilic addition feature. 12 Eexamples of β,β‐dicyanostyrene derivatives have been investigated.
A Novel and Facile Synthesis of 2‐(Benzofuran‐2‐yl)benzo[h]quinoline‐3‐carboxylic Acid Derivatives
Authors: Gao Wentao , Jiang Yun , Li Yang , Li Feng , Yan Yan 
Published: March 2012

AbstractA simple and concise approach for the synthesis of a series of new heterocyclic systems of 2‐(benzofuran‐2‐yl)benzo[h]quinoline‐3‐carboxylic acid derivatives (3a–3g) is described. The synthetic strategy features the one‐pot reaction of ethyl 2‐(chloromethyl)benzo[h]quinoline‐3‐carboxylate (2) with various substituted salicylaldehydes as well as 2‐hydroxy‐1‐naphthaldehyde as a key step. The substrate 2 was prepared in good yield by a mild, efficient and direct reaction of 1‐naphthylamine (1) with Vilsmeier‐Haack reagent. The structures of all the new compounds were identified by spectral data and elemental analysis.
Michael Addition Reaction of Fluorinated Nitro Compounds
Authors: Huan Feng , Hu Huawei , Huang Yangen , Chen Qingyun , Guo Yong 
Published: March 2012

AbstractThe Michael addition reactions of fluorinated nitro compounds with electron deficient olefins to give γ‐fluoro‐γ‐nitro‐esters, nitriles and ketones which bear a fluorinated quaternary carbon center were reported. The reactions were promoted by TMG, affording the desired adducts in acceptable to good yields.
Water‐Promoted Kinetic Separation of trans‐ and cis‐Limonene Oxides
Authors: Xu Zhao‐Bing , Qu Jin 
Published: March 2012

AbstractThe efficient hydrolytic kinetic separation of trans/cis‐(R)‐(+)‐limonene oxides was realized in a 1:1 mixed solvent of water and 1,4‐dioxane without additional catalyst. Optically pure trans‐(R)‐(+)‐limonene oxide was recovered in high yield (77%).
Synthesis, Characterization and Ethylene Oligomerization Behavior of Neutral Nickel Complexes Bearing N‐Fluorinated Phenyl Salicylaldiminato Chelate Ligands
Authors: Song Liping , Song Shaodi , Huang Jiling 
Published: March 2012

AbstractA series of neutral nickel complexes featuring N‐fluorinated phenyl salicylaldiminato chelate ligands was synthesized, and the novel molecular structure of complex C14 was further confirmed by X‐ray crystallographic analysis. The neutral nickel complexes showed high activity up to 9.96×105 g oligomers/(mol Ni·h) and high selectivity of C6 in catalyzing ethylene oligomerization using methylaluminoxane (MAO) as cocatalyst. It was observed that the strong electron‐withdrawing effect of the fluorinated salicylaldiminato ligand was able to significantly increase the catalytic activity for oligomerization of ethylene. In addition, the influence of reaction parameters such as Al/Ni molar ratio, reaction temperature, a variety of cocatalyst and ethylene pressure on catalytic activity was investigated.
Determination of Uric Acid in Human Urine by Ion‐exclusion Chromatography with UV Detection Using Pure Water as Mobile Phase
Authors: Hou Shengjie , Yang Chengdui , Wang Hui , Tanaka Kazuhiko , Ding Mingyu 
Published: March 2012

AbstractA simple, rapid and accurate ion‐exclusion chromatographic method coupled with a UV detector for the determination of uric acid in human urine samples has been developed. The separation was carried out on an ion‐exclusion column using only pure water as mobile phase. The detection wavelength was 254 nm and urine sample was injected directly without any pretreatment. Furthermore, the retention behavior of uric acid on the ion‐exclusion column was researched when pure water and 1 mmol·L−1 HCl were used as mobile phase, respectively. The stability of uric acid was also further investigated within 28 days. In this method, the linear range of the calibration curve for uric acid was 0.25–100 mg·L−1, and the detection limit calculated at S/N=3 was 0.02 mg·L−1. The proposed ion‐exclusion chromatographic method has been used for the determination of uric acid in human urine.
The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53
Authors: Carney Bruce K. , Caruso Silva Victoria , Cassimeris Lynne 
Published: March 2012

AbstractIn several cancer cell lines, depleting the microtubule (MT)‐destabilizing protein stathmin/oncoprotein18 leads to a G2 cell cycle delay and apoptosis. These phenotypes are observed only in synergy with low levels of p53, but the pathway(s) activated by stathmin depletion to delay the cell cycle are unknown. We found that stathmin depletion caused greater MT stability in synergy with loss of p53, measured by the levels of acetylated α‐tubulin and the rate of centrosomal MT nucleation. Nocodazole or vinblastine‐induced MT depolymerization abrogated the stathmin‐depletion induced G2 delay, measured by the percentage of cells staining positive for several markers (TPX2, CDK1 with inhibitory phosphorylation), indicating that MTs are required to lengthen G2. Live cell imaging showed that stathmin depletion increased time in G2 without an impact on the duration of mitosis, indicating that the longer interphase duration is not simply a consequence of a previous slowed mitosis. In contrast, stabilization of MTs with paclitaxel (8 nM) slowed mitosis without lengthening the duration of interphase, demonstrating that increased MT stability alone is not sufficient to delay cells in G2. © 2012 Wiley Periodicals, Inc
Structural and Pharmacological Characterization of Phenylalanine‐Based AMPA Receptor Antagonists at Kainate Receptors
Authors: Venskutonytė Raminta , Frydenvang Karla , Valadés Elena Antón , Szymańska Ewa , Johansen Tommy N. , Kastrup Jette S. , Pickering Darryl S. 
Published: March 2012

AbstractContinued efforts into the discovery of ligands that target ionotropic glutamate receptors (iGluRs) are important for studies of the physiological roles of the various iGluR subtypes as well as for the search for drugs that can be used in the treatment of diseases of the central nervous system. A new series of phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors. Herein we report our studies of these compounds at the kainate receptors GluK1–3. Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not bind GluK2. The crystal structure of the most potent compound in the ligand binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2, due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a domain closure similar to that observed in GluK1 structures with partial agonists.
Neuronal clustering and fasciculation phenotype in Dscam‐ and Bax‐deficient mouse retinas
Authors: Keeley Patrick W. , Sliff Buranee J. , Lee Sammy C.S. , Fuerst Peter G. , Burgess Robert W. , Eglen Stephen J. , Reese Benjamin E. 
Published: March 2012

AbstractWild‐type mouse retina immunofluorescently labeled to reveal the populations of melanopsin‐positive ganglion cells (green) and dopaminergic amacrine cells (magenta). Each cell type shows abnormal clustering and fasciculation in both Dscam‐ and Bax‐ deficient mice, though the profile of these features is distinct in the two mutants. The Journal of Comparative Neurology, Volume 520, Number 7, pages 1349–1364.
Selective Production of 1,2‐Propylene Glycol from Jerusalem Artichoke Tuber using Ni–W2C/AC Catalysts
Authors: Zhou Likun , Wang Aiqin , Li Changzhi , Zheng Mingyuan , Zhang Tao 
Published: March 2012

AbstractA series of Ni‐promoted W2C/activated carbon (AC) catalysts were investigated for the catalytic conversion of Jerusalem artichoke tuber (JAT) under hydrothermal conditions and hydrogen pressure. Even a small amount of Ni could greatly promote the conversion of JAT to 1,2‐propylene glycol (1,2‐PG), whereas the pure W2C/AC catalyst resulted in the selective formation of acetol. The product distribution profiles involving the reaction temperature, time, and H2 pressure indicated that 1,2‐PG formed as a result of acetol hydrogenation, which was catalyzed by Ni. Thus, there was a synergy between W2C and Ni, and the best performance yielded 38.5 % of 1,2‐PG over a 4 % Ni–20 % W2C/AC catalyst at 245 °C, 6 MPa H2, and 80 min. To understand the reaction process, some important intermediates, such as inulin, fructose, acetol, glyceraldehyde, and 1,3‐dihydroxyacetone, were used as the feedstock. Based on the product distributions derived from these intermediates, a reaction pathway was proposed, where JAT was first hydrolyzed into a mixture of fructose and glucose under the catalysis of H+, then the sugars underwent a retro‐aldol reaction followed by hydrogenation catalyzed by Ni–W2C.
A novel and rapid apoptosis assay based on thiol redox status
Authors: Skindersoe Mette E. , Rohde Mikkel , Kjaerulff Soeren 
Published: March 2012

AbstractWe present here a novel probe, VitaBright‐48, for the evaluation of the cellular level of reduced thiols. Using different cell lines and apoptogenic agents we show that a decrease in the level of reduced thiols correlates with well‐known apoptotic markers such as phosphatidylserine translocation and caspase activity. The cell population to be investigated is added to the nonfluorescent stain VitaBright‐48, which immediately permeates the cell membrane and reacts with intracellular thiols, forming a fluorescent compound. Quantification of the cell fluorescence directly after staining (without washing) can then be used to determine the population's cellular thiol level at the single cell level. Based on the results presented here, we suggest that measurement of changes in the level of free thiols should be added to the list of phenotypes which may be investigated in order to detect apoptosis. © 2012 International Society for Advancement of Cytometry
Maternal care in the African striped mouse Rhabdomys pumilio: A behaviorally flexible phenotype that is modified by experience
Authors: Rymer Tasmin L. , Pillay Neville 
Published: March 2012

AbstractThe development of maternal care in mammals can be influenced by the type and quality of maternal care received. Using biparental striped mice Rhabdomys pumilio, we investigated whether development of maternal care is influenced by the mother during early rearing and by an adult female's experience and that of her mate. Offspring were raised in one of three treatments, by: both parents; mothers alone; and mothers separated from the father with a barrier. Since female striped mice increase their care when raising litters alone, which influences expression of parental care of their adult sons, we expected daughters to respond like sons. However, there was no treatment effect in the development of maternal care in daughters. In subsequent experiments, experienced and inexperienced females decreased care when raising their offspring with experienced but not inexperienced males. Therefore, maternal care in striped mice is modulated in response to prevailing environmental and social conditions. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 265–274, 2013