bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualization of human immunodeficiency virus protease inhibition using a novel Förster resonance energy transfer molecular probe
Authors: Jin Sha , Ellis Erika , Veetil Jithesh V. , Yao Huantong , Ye Kaiming 
Published: April 2011

AbstractThe in vivo high‐throughput screening (HTS) of human immunodeficiency virus (HIV) protease inhibitors is a significant challenge because of the lack of reliable assays that allow the visualization of HIV targets within living cells. In this study, we developed a new molecular probe that utilizes the principles of Förster resonance energy transfer (FRET) to visualize HIV‐1 protease inhibition within living cells. The probe is constructed by linking two fluorescent proteins: AcGFP1 (a mutant green fluorescent protein) and mCherry (a red fluorescent protein) with an HIV‐1 protease cleavable p2/p7 peptide. The cleavage of the linker peptide by HIV‐1 protease leads to separation of AcGFP1 from mCherry, quenching FRET between AcGFP1 and mCherry. Conversely, the addition of a protease inhibitor prevents the cleavage of the linker peptide by the protease, allowing FRET from AcGFP1 to mCherry. Thus, HIV‐1 protease inhibition can be determined by measuring the FRET signal's change generated from the probe. Both in vitro and in vivo studies demonstrated the feasibility of applying the probe for quantitative analyses of HIV‐1 protease inhibition. By cotransfecting HIV‐1 protease and the probe expression plasmids into 293T cells, we showed that the inhibition of HIV‐1 protease by inhibitors can be visualized or quantitatively determined within living cells through ratiometric FRET microscopy imaging measurement. It is expected that this new probe will allow high‐content screening (HCS) of new anti‐HIV drugs. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Process development and cGMP manufacturing of a recombinant ricin vaccine: An effective and stable recombinant ricin a‐chain vaccine—RVEc™
Authors: Meagher Michael M. , Seravalli Javier G. , Swanson S. Todd , Ladd Roger G. , Khasa Yogender P. , Inan Mehmet , Harner Jay C. , Johnson Scott K. , Van Cott Kevin , Lindsey Changhong , Wannemacher Robert , Smith Leonard A. 
Published: April 2011

AbstractRicin is a potent toxin and a potential bioterrorism weapon with no specific countermeasures or vaccines available. The holotoxin is composed of two polypeptide chains linked by a single disulfide bond: the A‐chain (RTA), which is an N‐glycosidase enzyme, and the B‐chain (RTB), a lectin polypeptide that binds galactosyl moieties on the surface of the mammalian target cells. Previously (McHugh et al.), a recombinant truncated form of RTA (rRTA1‐33/44‐198 protein, herein denoted RVEa™) expressed in Escherichia coli using a codon‐optimized gene was shown to be non‐toxic, stable, and protective against a ricin challenge in mice. Here, we describe the process development and scale‐up at the 12 L fermentation scale, and the current Good Manufacturing Practice (cGMP)‐compliant production of RVEc™ at the 40 L scale. The average yield of the final purified bulk RVEc™ is approximately 16 g/kg of wet cell weight or 1.2 g/L of fermentation broth. The RVEc™ was >99% pure by three HPLC methods and SDS‐PAGE. The intact mass and peptide mapping analysis of RVEc™ confirmed the identity of the product and is consistent with the absence of posttranslational modifications. Potency assays demonstrated that RVEc™ was immunoprotective against lethal ricin challenge and elicited neutralizing anti‐ricin antibodies in 95–100% of the vaccinated mice. Published 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011.
Isolation and characterization of a subset of erythropoietin glycoforms with cytoprotective but minimal erythropoietic activity
Authors: Mattio Mónica , Ceaglio Natalia , Oggero Marcos , Perotti Norma , Amadeo Ignacio , Orozco Gustavo , Forno Guillermina , Kratje Ricardo , Etcheverrigaray Marina 
Published: April 2011

AbstractAlthough historically used for the treatment of anemia, erythropoietin (EPO) has emerged as a neurotrophic and neuroprotective agent in different conditions of neuronal damage (traumatic brain injury, ischemia, spinal cord compression, peripheral neuropathy, retinal damage, epilepsy, Parkinson's Disease, among others). Nonetheless, EPO's therapeutic application is limited due to its hematological side‐effects. With the aim of obtaining EPO derivatives resembling the hormone isolated from cells and tissues of neural origin, a novel combination of less acidic EPO glycoforms ‐designated as neuroepoetin (rhNEPO)‐ was purified to homogeneity from the supernatant of a CHO‐producing cell line by a four‐step chromatographic procedure. This simple and single process allowed us to prepare two EPO derivatives with distinct therapeutic expectations: the hematopoietic version and a minimally hematopoietic, but mainly in vitro cytoprotective, alternative. Further biological characterization showed that the in vivo erythropoietic activity of rhNEPO was 25‐times lower than that of rhEPO. Interestingly, using different in vitro cytoprotective assays we found that this molecule exerts cytoprotection equivalent to, or better than, that of rhEPO in cells of neural phenotype. Furthermore, despite its shorter plasma half‐life, rhNEPO was rapidly absorbed and promptly detected in the cerebrospinal fluid after intravenous administration in rats (5 min postinjection, in comparison with 30 min for rhEPO). Therefore, our results support the study of neuroepoetin as a potential drug for the treatment of neurological diseases, combining high cytoprotective activity with reduced hematological side‐effects. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
CFD‐aided cell settler design optimization and scale‐up: Effect of geometric design and operational variables on separation performance
Authors: Shen Yuyi , Yanagimachi Kurt 
Published: April 2011

AbstractThe inclined multiplate (lamella) gravity settler has proven to be an effective cell retention device in industrial perfusion cell culture applications. Investigations on the effects of geometric design and operational variables of the cell settler are crucial to understanding how to best improve the settler performance. Maximizing the harvest/perfusion flow rate while minimizing viable cell loss out of the harvest is the primary challenge for optimization of the settler design. This study demonstrated that computational fluid dynamics (CFD) can be utilized to accurately model and evaluate the settler separation performance for near‐monodisperse suspensions and therefore aid in the design optimization of the settler under these baseline conditions. With the preferred geometric features that were identified from CFD modeling results, we proposed design guidelines for the scale‐up of these multiplate settler systems. With these guidelines and performance verification using the CFD model, a new large‐scale settler was designed and fabricated for a perfusion cell culture process using a minimally aggregating production cell line. Perfusion cell culture runs with this particular cell line were performed with this settler, and the CFD model was able to predict the initial ramp‐up performance, proving it to be a valuable scale‐up design tool for this production process. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Phenoxazine Dyes for Dye‐Sensitized Solar Cells: Relationship Between Molecular Structure and Electron Lifetime
Authors: Karlsson Karl Martin , Jiang Xiao , Eriksson Susanna K , Gabrielsson Erik , Rensmo Håkan , Hagfeldt Anders , Sun Licheng 
Published: April 2011

AbstractA series of metal‐free organic dyes with a core phenoxazine chromophore have been synthesized and tested as sensitizers in dye‐sensitized solar cells. Overall conversion efficiencies of 6.03–7.40 % were reached under standard AM 1.5G illumination at a light intensity of 100 mW cm−2. A clear trend in electron lifetime could be seen; a dye with a furan‐conjugated linker showed a shorter lifetime relative to dyes with the acceptor group directly attached to the phenoxazine. The addition of an extra donor unit, which bore insulating alkoxyl chains, in the 7‐position of the phenoxazine could increase the lifetime even further and, together with additives in the electrolyte to raise the conduction band, an open circuit voltage of 800 mV could be achieved. From photoelectron spectroscopy and X‐ray absorption spectroscopy of the dyes adsorbed on TiO2 particles, it can be concluded that the excitation is mainly of cyano character (i.e., on average, the dye molecules are standing on, and pointing out, from the surface of TiO2 particles).
Porphyrin‐Based Switchable Molecular Turnstiles
Authors: Guenet Aurélie , Graf Ernest , Kyritsakas Nathalie , Hosseini Mir Wais 
Published: April 2011

AbstractThe design, synthesis and structural characterisation, in solution, of two new molecular turnstiles based on Sn–porphyrin derivatives are described. The system is composed of a stator (5‐(4‐pyridyl)‐10,15,20‐triphenylporphyrin), a hinge (SnIV) and a rotor (handle equipped with 2,6‐pyridinedicarboxamide as a tridentate coordinating site or its PdII complex). The presence of interaction sites, both on the stator and the rotor, offers the possibility of switching between an open state (free rotation of the handle around the porphyrin) and a closed state (blockage of the rotation) by either establishment of hydrogen bonds between the stator and the rotor or by the simultaneous binding of Pd by both coordinating groups.
Direct Arylation of Heteroaromatic Compounds with Congested, Functionalised Aryl Bromides at Low Palladium/Triphosphane Catalyst Loading
Authors: Roy David , Mom Sophal , Lucas Dominique , Cattey Hélène , Hierso Jean‐Cyrille , Doucet Henri 
Published: April 2011

AbstractA new ferrocenyl triphosphane ligand associated to palladium was found to be an efficient catalyst for the direct coupling of highly congested, functionalised aryl bromides with a variety of heteroarenes. These coupling reactions can generally be performed by using a low‐loading (0.1–0.5 mol %) of the catalyst. The present protocol tolerates important and useful functional groups, which allows for further elaboration into more sophisticated heterocyclic molecules. The straightforward arylation of heteroaromatic compounds with congested ortho‐substituted aryl bromides may permit further convergent syntheses of diverse ligands, biologically active molecules and molecular materials in only a few steps.
Current Methods for Asymmetric Halogenation of Olefins
Authors: Castellanos Alejandro , Fletcher Stephen P. 
Published: April 2011

AbstractThis Minireview discusses the progress made in developing reactions where an olefin is subjected to an asymmetric halogenation. It aims to serve as a reference for the studies reported to date, including preliminary work and mechanistic studies. The current state of the art, scope, and limitations of these processes are discussed.
Contribution of Explicit Solvent Effects to the Binding Affinity of Small‐Molecule Inhibitors in Blood Coagulation Factor Serine Proteases
Authors: Abel Robert , Salam Noeris K. , Shelley John , Farid Ramy , Friesner Richard A. , Sherman Woody 
Published: April 2011

AbstractThe prevention of blood coagulation is important in treating thromboembolic disorders, and several serine proteases involved in the coagulation cascade have been classified as pharmaceutically relevant. Whereas structure‐based drug design has contributed to the development of some serine protease inhibitors, traditional computational methods have not been able to fully describe structure–activity relationships (SAR). Here, we study the SAR for a number of serine proteases by using a method that calculates the thermodynamic properties (enthalpy and entropy) of the water that solvates the active site. We show that the displacement of water from specific subpockets (such as S1–4 and the ester binding pocket) of the active site by the ligand can govern potency, especially for cases in which small chemical changes (i.e., a methyl group or halogen) result in a substantial increase in potency. Furthermore, we describe how relative binding free energies can be estimated by combining the water displacement energy with complementary terms from an implicit solvent molecular mechanics description binding.
Development of Novel Peptidomimetics Containing a Vinyl Sulfone Moiety as Proteasome Inhibitors
Authors: Ettari Roberta , Bonaccorso Cinzia , Micale Nicola , Heindl Cornelia , Schirmeister Tanja , Calabrò Maria Luisa , Grasso Silvana , Zappalà Maria 
Published: April 2011

AbstractProteasome inhibition is a topic of great interest in anticancer research. The proteolytic activity of this multicatalytic complex relies on three subunits, β1, β2 and β5, containing a caspase‐like, a trypsin‐like and a chymotrypsin‐like active site, respectively. Several studies have demonstrated that, of the three activities, the chymotrypsin‐like activity was the most necessary for cell viability and protein processing. Thus, most efforts towards the development of proteasome inhibitors have focused on the selective inhibition of the β5 subunit active site. Herein, we report the design and synthesis of a series of conformationally constrained tripeptidyl vinyl sulfones were determined to be good inhibitors of the chymotrypsin‐like activity of proteasome, with KI values in the sub‐micromolar to micromolar range. These compounds were also tested against bovine pancreatic α‐chymotrypsin and human cathepsin B and L, revealing a good selectivity for the target enzyme over these related enzymes.
Dissociative Electron Attachment to β‐Alanine
Authors: Vizcaino Violaine , Bartl Peter , Gschliesser David , Huber Stefan E. , Probst Michael , Märk Tilmann D. , Scheier Paul , Denifl Stephan 
Published: April 2011

AbstractA detailed study on dissociative electron attachment (DEA) to β‐alanine (βA) in the gas phase is presented. Ion yields as a function of the incident electron energy from about 0 to 15 eV have been measured for most of the fragments. As for all α‐amino acids, the main reaction corresponds to the loss of a hydrogen atom, although many other fragments have been observed that involved more complex bond cleavages. Threshold energies have been calculated by using the G4(MP2) method for various decomposition reactions. Fragmentation pathways were also investigated to measure metastable decays of the intermediate fragment anion (βA−H)− by using the mass‐analyzed ion kinetic energy (MIKE) scan technique. Comparisons with α‐alanine and other amino acids are made when relevant.
Correlation between Luminescence and EPR Spectroscopy as Evidence of Ytterbium Pair Formation in Li6Ln(BO3)3:Yb3+ (Ln=Gd, Y) Borate Single Crystals
Authors: Jubera Véronique , Chavoutier Marie , Artemenko Alla , Veber Philippe , Velazquez Matias , Garcia Alain 
Published: April 2011

AbstractSynthesized powders and grown single crystals of nominal compositions Li6Ln(BO3)3:Yb3+ (Ln=Y, Gd) were investigated by means of powder and single‐crystal X‐ray diffraction (XRD), as well as optical near‐IR spectroscopy in conjunction with electron paramagnetic resonance (EPR) spectroscopy. The appearance of two distinct zero‐phonon lines suggests the existence of two kinds of Yb3+ ions in the single crystals. The XRD results exclude the possibility of a phase transition occurring between room and low temperatures. EPR spectra of single crystals show the presence of both isolated ions and pairs of ytterbium ions substituted for Y3+. A strong temperature dependence of the intensity of Yb–Yb pairs resonance lines coincides with temperature dependence of emission peak at 978 nm, confirming a common origin of the defect giving rise to these spectra. Calculated from EPR spectra, the distance between pairs of Yb3+ is in good agreement with crystallographic ones: R=3.856 Å, Rcryst=3.849 Å.
Semiquinone Intermediates in the Two‐Electron Reduction of Quinones in Aqueous Media and their Exceptionally High Reactivity towards Oxygen Reduction
Authors: Li Qian , Batchelor‐McAuley Christopher , Lawrence Nathan S. , Hartshorne Robert S. , Compton Richard G. 
Published: April 2011

AbstractWe report the catalytic anthraquinone‐mediated reduction of oxygen at a boron‐doped diamond electrode. Scheme of squares modelling confirms the existence of and reveals the role of the semiquinone intermediates, which are shown to have an exceptional reactivity towards oxygen (as compared to the di‐reduced anthraquinone).
Design of Ru–Zeolites for Hydrogen‐Free Production of Conjugated Linoleic Acids
Authors: Philippaerts An , Goossens Steven , Vermandel Walter , Tromp Moniek , Turner Stuart , Geboers Jan , Van Tendeloo Gustaaf , Jacobs Pierre A. , Sels Bert F. 
Published: April 2011

AbstractWhile conjugated vegetable oils are currently used as additives in the drying agents of oils and paints, they are also attractive molecules for making bio‐plastics. Moreover, conjugated oils will soon be accepted as nutritional additives for “functional food” products. While current manufacture of conjugated vegetable oils or conjugated linoleic acids (CLAs) uses a homogeneous base as isomerisation catalyst, a heterogeneous alternative is not available today. This contribution presents the direct production of CLAs over Ru supported on different zeolites, varying in topology (ZSM‐5, BETA, Y), Si/Al ratio and countercation (H+, Na+, Cs+). Ru/Cs‐USY, with a Si/Al ratio of 40, was identified as the most active and selective catalyst for isomerisation of methyl linoleate (cis‐9,cis‐12 (C18:2)) to CLA at 165 °C. Interestingly, no hydrogen pre‐treatment of the catalyst or addition of hydrogen donors is required to achieve industrially relevant isomerisation productivities, namely, 0.7 g of CLA per litre of solvent per minute. Moreover, the biologically most active CLA isomers, namely, cis‐9,trans‐11, trans‐10,cis‐12 and trans‐9,trans‐11, were the main products, especially at low catalyst concentrations. Ex situ physicochemical characterisation with CO chemisorption, extended X‐ray absorption fine structure measurements, transmission electron microscopy analysis, and temperature‐programmed oxidation reveals the presence of highly dispersed RuO2 species in Ru/Cs‐USY(40).
Power‐efficient analog design based on the class AB super source follower
Authors: Lopez‐Martin Antonio J. , Acosta Lucia , Garcia‐Alberdi Coro , Carvajal Ramon G. , Ramirez‐Angulo Jaime 
Published: April 2011

SUMMARYA class AB version of the conventional super source follower (SSF) is described. The circuit greatly increases slew rate (SR) and current efficiency, maintaining the low distortion and low output resistance of the SSF. Class AB operation is achieved without extra power dissipation or supply requirements, and without bandwidth or noise degradation. The circuit can advantageously replace the SSF in a wide variety of analog systems, opening a new research line in analog design. To illustrate the widespread application of this cell, a class AB differential unity‐gain buffer, a class AB differential current mirror and two class AB differential transconductors are designed, fabricated in a 0.5µm CMOS technology and tested. Measurement results using a dual supply of ±1.65V show that the proposed class AB version of the SSF improves SR by a factor 21.5 and increases bandwidth by 10%, keeping noise level, input range, power consumption, and supply requirements unaltered. The fabricated class AB current mirror features a THD at 100 kHz of − 62dB for signal currents 20 times larger than the bias current. The fabricated transconductors feature an IM3 at 1 MHz of − 56.6dB for output currents more than 13 times larger than the bias currents. Copyright © 2011 John Wiley & Sons, Ltd.
The synaptic cytoskeleton in development and disease
Authors: Goellner Bernd , Aberle Hermann 
Published: April 2011

AbstractThe cytoskeleton forms the backbone of neuronal architecture, sustaining its form and size, subcellular compartments and cargo logistics. The synaptic cytoskeleton can be categorized in the microtubule‐based core cytoskeleton and the cortical membrane skeleton. While central microtubules form the fundamental basis for the construction of elaborate neuronal processes, including axons and synapses, cortical actin filaments are generally considered to function as mediators of synapse dynamics and plasticity. More recently, the submembranous network of spectrin and ankyrin molecules has been involved in the regulation of synaptic stability and maintenance. Disruption of the synaptic cytoskeleton primarily affects the stability and maturation of synapses but also secondarily disturbs neuronal communication. Consequently, a variety of inherited diseases are accompanied by cytoskeletal malfunctions, including spastic paraplegias, spinocerebellar ataxias, and mental retardation. Since the primary reasons for many of these diseases are still unknown model organisms with a conserved repertoire of cytoskeletal elements help to understand the underlying biological mechanisms. The astonishing technical as well as genetic accessibility of synapses in Drosophila has shown that loss of the cytoskeletal architecture leads to axonal transport defects, synaptic maturation deficits, and retraction of synaptic boutons, before synaptic terminals finally detach from their target cells, suggesting that similar processes could be involved in human neuronal diseases. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 111–125, 2012
3D expression patterns of cell cycle genes in the developing chick wing and comparison with expression patterns of genes implicated in digit specification
Authors: Welten Monique , Pavlovska Gordana , Chen Yu , Teruoka Yuko , Fisher Malcolm , Bangs Fiona , Towers Matthew , Tickle Cheryll 
Published: April 2011

AbstractSonic hedgehog (Shh) signalling controls integrated specification of digit pattern and growth in the chick wing but downstream gene networks remain to be unravelled. We analysed 3D expression patterns of genes encoding cell cycle regulators using Optical Projection Tomography. Hierarchical clustering of spatial matrices of gene expression revealed a dorsal layer of the wing bud, in which almost all genes were expressed, and that genes encoding positive cell cycle regulators had similar expression patterns while those of N‐myc and CyclinD2 were distinct but closely related. We compared these patterns computationally with those of genes implicated in digit specification and Ptch1, 50 genes in total. Nineteen genes have similar posterior expression to Ptch1, including Hoxd13, Sall1, Hoxd11, and Bmp2, all likely Gli targets in mouse limb, and cell cycle genes, N‐myc, CyclinD2. We suggest that these genes contribute to a network integrating digit specification and growth in response to Shh. Developmental Dynamics 240:1278–1288, 2011. © 2011 Wiley‐Liss, Inc.
Summary of ‘Lactulose versus polyethylene glycol for chronic constipation’
Authors: Canadian Editorial Office Evidence‐Based Child Health 
Published: April 2011

AbstractThis is a summary of a Cochrane review, published in this issue of EBCH, first published as: Lee‐Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD007570. DOI: 10.1002/14 651 858.CD007570.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Lactulose versus polyethylene glycol for chronic constipation’
Authors: Vandenplas Yvan , Greef Elisabeth De , Smeets Nathalie , Hauser Bruno 
Published: April 2011

AbstractThis is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Lee‐Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD007570. DOI: 10.1002/14 651 858.CD007570.pub2.Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration