bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for a molecular mechanism of teratogenicity of SB‐236057, a 5‐HT1B receptor inverse agonist that alters axial formation
Authors: Augustine‐Rauch Karen A. , Zhang Qin J. , Leonard Jennifer L. , Chadderton Antony , Welsh Michael J. , Rami Harshad K. , Thompson Mervyn , Gaster Laramie , Wier Patrick J. 
Published: October 2004

AbstractBACKGROUNDSB‐236057 is a potent skeletal teratogen in rodents and rabbits, producing axial and posterior somite malformations in cultured rat embryos. The compound shares some structural similarity to cyclopamine.METHODSM13 phage display was used to identify amino acid motifs with binding affinity to SB‐236057. A 10 μM SB‐236057 solution was administered to cultured day 9 postcoitus rat embryos and real‐time PCR was conducted at 6 hr posttreatment to evaluate early transcriptional response of axial development genes. Whole‐mount in situ hybridization of selected transcripts was conducted on embryos at 48 hr post‐compound administration. The rat‐enhancer of split protein 1 (r‐esp1) expression‐functional characterization was done by transcriptional expression and morpholino antisense approaches.RESULTSWe identified several amino acid motifs that had high binding affinity to SB‐236057‐biotin conjugates, one with 100% sequence homology to a region of r‐esp1, one of the Groucho homologs transcribed by the enhancer of split complex (En[spl]C). SB‐236057 repressed expression of r‐esp1 and members of the Notch‐En[spl]C pathway. Goosecoid and HNF3‐β, both suspected to associate with Groucho proteins, were also responsive, although expression of another putative binding protein, engrailed‐1 (en‐1), and other en‐1 pathway members was not affected. R‐esp1 mRNA was localized along the axis and antisense inhibition produced similar somite malformations as SB‐236057 did. At 48 hr post–SB‐236057 or post–r‐esp1 antisense administration, affected embryos demonstrated unchanged sonic hedgehog (shh) expression, however HNF3‐β expression was either absent, altered, or reduced.CONCLUSIONSWe present experimental evidence that the mechanism of SB‐236057 teratogenicity includes transcriptional alterations to the Notch1‐En[spl] pathway. In addition, alterations in HNF3‐β expression were similar to those induced by cyclopamine. The relationships between r‐esp1 with Notch1 and shh signaling pathways and potential mechanisms of SB‐236057 teratogenicity are also discussed. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
Highly efficient baculovirus‐mediated gene transfer into rat chondrocytes
Authors: Ho Yi‐Chen , Chen Huang‐Chi , Wang Kuei‐Chun , Hu Yu‐Chen 
Published: October 2004

AbstractTo explore the potential of baculovirus serving as a gene delivery vector in tissue engineering of articular cartilage, the efficiencies of baculovirus‐mediated gene delivery into primary rat chondrocytes were evaluated and the transduction protocol commonly employed by others (using concentrated virus at multiplicity of infection [MOI] 200 for 1 h) was found to be ineffective (<1%). Therefore, a modified protocol was adopted, which markedly enhanced the efficiency (68%). Optimization of the transduction parameters, such as incubation time (8 h), temperature (25°C), and surrounding solutions (PBS), further increased the efficiency to 88% and prolonged the duration of expression to 21 days, suggesting that the cells previously considered nonpermissive to baculovirus transduction may be reexamined for their permissiveness using alternative transduction protocols. The elevated efficiency correlated well with increased virus uptake upon extended incubation time, as demonstrated by quantitative real‐time polymerase chain reaction (Q‐PCR). The Q‐PCR also revealed the degradation of viral DNA over culture time. Although the virus transduction somewhat hindered the cell proliferation, growth rate could be restored in the long‐term culture. More importantly, transduced cells could secrete articular cartilage‐specific type II collagen and glycosaminoglycan as well as mock‐transduced cells, confirming that normal differentiation state of rat chondrocytes is retained upon baculovirus transduction. Taken together, these data indicate that baculovirus is a safe and highly efficient gene delivery vehicle into rat chondrocytes. © 2004 Wiley Periodicals, Inc.
Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp. ATCC 39727
Authors: Gunnarsson Nina , Bruheim Per , Nielsen Jens 
Published: October 2004

AbstractThe actinomycete Nonomuraea sp. ATCC 39727, producer of the glycopeptide A40926 that is used as precursor for the novel antibiotic dalbavancin, has an unusual carbon metabolism. Glucose is primarily metabolized via the Entner–Doudoroff (ED) pathway, although the energetically more favorable Embden–Meyerhof–Parnas (EMP) pathway is present in this organism. Moreover, Nonomuraea utilizes a PPi‐dependent phosphofructokinase, an enzyme that has been connected with anaerobic metabolism in eukaryotes and higher plants, but recently has been recognized in several actinomycetes. In order to study its primary carbon metabolism in further detail, Nonomuraea was cultivated with [1‐13C] glucose as the only carbon source and the 13C‐labeling patterns of proteinogenic amino acids were determined by GC‐MS analysis. Through this method, the fluxes in the central carbon metabolism during balanced growth were estimated. Moreover, a shift in the label incorporation pattern was observed in connection with phosphate limitation and increased antibiotic productivity in Nonomuraea. The shift indicated an increased flux through the EMP pathway at the expense of the flux through the ED pathway, a suggestion that was supported by alterations in intracellular metabolite levels during phosphate limitation. In contrast, expression levels of genes encoding enzymes in the ED and EMP pathways were not affected by phosphate limitation. © 2004 Wiley Periodicals, Inc.
Interaction of surface‐active drugs in rabbits
Authors: Rukhadze Marina D. , Alexishvili Maka M. , Gonashvili Maia V. , Sebiskveradze Maya V. 
Published: October 2004

AbstractThe interaction of chlorpromazine and promethazine in vivo has been investigated. The drugs were administered to the rabbit orally as a single dose (100 mg of each drug) as well as simultaneously with an interval of 15 min. The presence of multiple peaks at the separate administration of promethazine and chlorpromazine on the one hand, and increase of number of peaks, symbathic character of kinetic curves of mentioned drugs and its prolonged appearance in the systemic circulation of the blood by simultaneous administration on the other hand, may be explained by the intensive presystem metabolism and surface‐activity ability of these drugs, and by the periodic ‘lassitude’ of liver for their capture and elimination (either presystem or systemic). The micelle formation from these drugs in the gastro‐intestinal tract and formation of the mixed micelles on simultaneous administration were also taken into consideration. Chlorpromazine is more strongly captured by the liver at its ﬁrst pass through it than promethazine, from comparison of pharmacokinetics of these drugs administered separately. Therefore, chlorpromazine on simultaneous administration occupies the sites of the liver which were covered by promethazine at single dose, thereby substituting promethazine and promoting its transferral into the systemic blood circulation. This results in a large increase in promethazine content in blood, additional peaks appear and the presence of promethazine in the blood is prolonged. The inﬂuence of chlorpromazine on the kinetics of promethazine is especially obvious when chlorpromazine enters the organism ﬁrst and more easily occupies those sites in the liver which participate in the capture and elimination of both drugs. Concerning inﬂuence of promethazine on the kinetics of chlorpromazine, promethazine reinforces in some way the ability of liver to capture chlorpromazine, thereby intensifying the presystem metabolism of chlorpromazine and inhibiting its own metabolism. The analogous effect was observed in the study of the inﬂuence of promethazine on the kinetics of carbamazepine. Copyright © 2004 John Wiley & Sons, Ltd.
CFD Simulation of Liquid Film Flow on Inclined Plates
Authors: Gu F. , Liu C.J. , Yuan X.G. , Yu G.C. 
Published: October 2004

AbstractA two‐phase flow CFD model using the volume of fluid (VOF) method is presented for predicting the hydrodynamics of falling film flow on inclined plates, corresponding to the surface texture of structured packing. Using the proposed CFD model the influence of the solid surface microstructure, liquid properties and gas flow rate on the flow behavior was investigated. From the simulated results it was shown that under the condition of no gas flow the liquid flow patterns are dependent on the microstructure of the plates, and proper microstructuring of the solid surface will improve the formation of a continuous liquid film. It was also found that liquid properties, especially surface tension, play an important role in determining the thin‐film pattern. However, there are very different liquid film patterns under the action of gas flow. Thinner liquid films break easily, but thicker liquid films can remain continuous even at higher gas flow rates, which demonstrates that all factors affecting the liquid film thickness will affect the liquid film patterns under conditions of counter‐current two‐phase flow.
Adsorption Equilibrium and Adsorption Kinetics: A Unified Approach
Authors: Islam Md.A. , Khan Md.M.R. , Mozumder Md.S.I. 
Published: October 2004

AbstractConventional methods for the characterization of adsorption systems (determination of equilibrium and kinetic parameters) have been discussed. It is shown that the kinetic parameters determined by conventional methods are completely inconsistent with the equilibrium parameters. This inconsistency is due to the application of completely different models for equilibrium and kinetic study. In the present study adsorption is viewed as a Langmuir type physico‐chemical reversible process and a three‐parameter model is proposed which describes an adsorption system from both equilibrium and kinetic viewpoints. The model satisfactorily describes the kinetic and the equilibrium data reported by previous authors.
The Use of the VOF‐Model to Study the Wetting of Solid Surfaces
Authors: Ataki A. , Bart H.‐J. 
Published: October 2004

AbstractThe laminar liquid rivulet flow on an inclined flat metal plate and wavy metal plate is taken as a test case to validate the CFD‐simulation results using the VOF (Volume of Fluid) multiphase flow model. The local rivulet thickness was measured using an optically assisted mechanical sensor and compared with the simulation results. The circular shape of the rivulet profile has been proven for an inclined plate. Glycerin water mixtures with different concentrations were used in the experiments. Two theoretical models to describe this laminar rivulet flow in comparison to the experimental and CFD results are discussed.
Washing Processes for Disperse Particulate Systems – Process Spectrum and Aspects for the Process Choice
Authors: Hoffner B. , Fuchs B. , Heuser J. 
Published: October 2004

AbstractWashing of disperse solid systems is a widely used and complex operation. Since the washing step is mostly integrated into other process operations, it is subject to numerous demands exceeding by far the primary demands, like a good separation result and a low specific wash liquid demand. Because of the phenomenology and limits of different washing processes it is difficult to choose an appropriate washing process. Additionally, the acting transport mechanisms of some washing processes are not yet sufficiently understood. This work gives a broad overview of the existing washing processes, the numerous parameters, and the demands they have to meet. Based on a categorization of washing processes and the classification of these processes according to their macroscopic transport phenomena, an evaluation scheme has been developed which compares and assesses existing washing processes and shows their individual limits. The present work can be used as a rough guideline for the choice of an appropriate washing process.
Multiple Binding Modes of the Camptothecin Family to DNA Oligomers
Authors: Bocian Wojciech , Kawȩcki Robert , Bednarek Elzbieta , Sitkowski Jerzy , Pietrzyk Agnieszka , Williamson Michael P. , Hansen Poul Erik , Kozerski Lech 
Published: October 2004

AbstractThe binding constants of camptothecin, topotecan and its lactone ring‐opened carboxylate derivative to DNA octamers were measured by UV and NMR spectroscopy. The self‐association of topotecan (TPT) was also measured. The carboxylate form of TPT binds in the same way as the lactone, but more weakly. Titration of TPT into d(GCGATCGC)2 shows a preferred location stacked onto the terminal G1 base. However, the intermolecular NOEs cannot be reconciled with a single conformation of the complex, and suggest a model of a limited number of conformations in fast exchange. MD calculations on four pairs of starting structures with TPT stacked onto the G1–C8 base pair in different orientations were therefore performed. The use of selected experimental “docking” restraints yielded ten MD trajectories covering a wide conformational space. From a combination of calculated free energies, NOEs and chemical shifts, some of the structures produced could be eliminated, and it is concluded that the data are consistent with two major families of conformations in fast exchange. One of these is the conformation found in a crystal of a TPT/DNA/topoisomerase I ternary complex [Proc. Natl. Acad. Sci. USA 2002, 99, 15 387–15 392].
RNA Is More UV Resistant than DNA: The Formation of UV‐Induced DNA Lesions is Strongly Sequence and Conformation Dependent
Authors: Kundu Lal Mohan , Linne Uwe , Marahiel Mohamed , Carell Thomas 
Published: October 2004

AbstractDNA and RNA hairpins, which represent well‐folded oligonucleotide structures, were irradiated and the amount of damaged hairpins was directly quantified by using ion‐exchange HPLC. The types of photoproducts formed in the hairpins were determined by ESI‐HPLC‐MS/MS experiments. Irradiation of hairpins with systematically varied sequences and conformations (A versus B) revealed remarkable differences regarding the amount of photolesions formed. UV‐damage formation is, therefore, a strongly sequence and conformation dependent process.
Lanthanide(III) Complexes of DOTA–Glycoconjugates: A Potential New Class of Lectin‐Mediated Medical Imaging Agents
Authors: André João P. , Geraldes Carlos F. G. C. , Martins José A. , Merbach André E. , Prata Maria I. M. , Santos Ana C. , de Lima João J. P. , Tóth Éva 
Published: October 2004

AbstractThe synthesis and characterization of a new class of DOTA (1,4,7,10‐tetrakis(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane) monoamide‐linked glycoconjugates (glucose, lactose and galactose) of different valencies (mono, di and tetra) and their SmIII, EuIII and GdIII complexes are reported. The 1H NMR spectrum of EuIII–DOTALac2 shows the predominance of a single structural isomer of square antiprismatic geometry of the DOTA chelating moiety and fast rotation about the amide bond connected to the targeting glycodendrimer. The in vitro relaxivity of the GdIII–glycoconjugates was studied by 1H nuclear magnetic relaxation dispersion (NMRD), yielding parameters close to those reported for other DOTA monoamides. The known recognition of sugars by lectins makes these glycoconjugates good candidates for medical imaging agents (MRI and gamma scintigraphy).
Regioselectivity in Iron‐Catalyzed [2+2+1] Cycloadditions: A DFT Investigation of Substituent Effects in 1,4‐Diazabutadienes
Authors: Imhof Wolfgang , Anders Ernst 
Published: October 2004

AbstractThe transition‐metal‐catalyzed [2+2+1] cycloaddition reaction of 1,4‐diazabutadienes, in which the imine‐carbon atoms are part of an oxazine ring system, with ethylene and carbon monoxide leads to the regioselective formation of pyrrolidinone derivatives. To explain this regioselectivity, the transition states and intermediates of the rate‐determining step of the catalysis are determined by high‐level DFT calculations. The experimentally observed regioselectivity is consistent with the lower activation energy of the addition of ethylene towards the carbon atom next to the oxazine oxygen atom. Furthermore, the activation barrier of a conceivable back reaction is higher for the intermediates with the experimentally observed regioselectivity. These thermodynamic and kinetic arguments at first sight appear to be confirmed by the calculated NPA charges in the transition states, which reveal that the differences in these charges are greatest for those transition states that lead to the formation of the energetically favored transition structures. Nevertheless, calculations of analogous transition structures and reaction products starting from 1,4‐diazabutadienes with a 2‐fluoro, 2‐hydroxo or 2‐amino substituent revealed that the regioselectivity is not determined by the electronegativity of the heteroatom and thus by the differences in the NPA charges or the resulting Coulombic interactions in the transition structures. The main reason for the observed regioselectivities is the π‐donor ability of the substituent to contribute to a delocalized π system incorporating the adjacent imine moiety. The increasing π‐donor capability results in decreased reactivity of this moiety and increases the (relative) reactivity of the second imine group. This effect can even overcompensate for strong intramolecular Coulombic attractions in the transition structures.
An Insight into a Novel Class of Self‐Assembled Porphyrins: Geometric Structure, Electronic Structure, One‐ and Two‐Photon Absorption Properties
Authors: Zhou Xin , Ren Ai‐Min , Feng Ji‐Kang 
Published: October 2004

AbstractWe have theoretically investigated a series of butadiyne‐linked porphyrin derivatives that exhibit large two‐photon absorption (TPA) cross sections in the visible‐IR range. The electronic structure, one‐photon absorption (OPA), and TPA properties have been studied in detail. We found that the introduction of a butadiyne linkage and the increase of the molecular dimensionality from monomer to dimer determine the OPA intensities of Q band and Soret band, respectively. A most important role for the enhancement of the TPA cross section is played by introducing a butadiyne bridge. The complementary coordination and the combination of the terminal free base and the core zinc porphyrin are also two effective factors for the enhancement of the TPA efficiency. The dimer with two porphyrins linked at meso‐positions by a butadiyne linkage results in a maximum TPA cross section (79.35×10−48 cm4 s per photon). Our theoretical findings are consistent with the recent experimental observations. This series of porphyrin derivatives as promising TPA materials are the subject of further investigation.
Novel Metathesis Catalysts Based on Ruthenium 1,3‐Dimesityl‐3,4,5,6‐tetrahydropyrimidin‐2‐ylidenes: Synthesis, Structure, Immobilization, and Catalytic Activity
Authors: Yang Liangru , Mayr Monika , Wurst Klaus , Buchmeiser Michael R. 
Published: October 2004

AbstractThe synthesis of novel ruthenium‐based metathesis catalysts containing the saturated 1,3‐bis(2,4,6‐trimethylphenyl)‐3,4,5,6‐tetrahydropyrimidin‐2‐ylidene ligand, that is, [RuCl2(NHC){CH‐2‐(2‐PrO)‐5‐NO2‐C6H3}] (1) and [Ru(CF3COO)2(NHC){CH‐2‐(2‐PrO)‐5‐NO2‐C6H3}] (2) (NHC=1,3‐bis(2,4,6‐trimethylphenyl)‐3,4,5,6‐tetrahydropyrimidin‐2‐ylidene) is described. Both catalysts are highly active in ring‐closing metathesis (RCM) and ring‐opening cross‐metathesis (ROCM). Compound 1 shows moderate activity in enyne metathesis. Compound 2 is not applicable to enyne metathesis since it shows high activity in the cyclopolymerization of diethyl dipropargylmalonate (DEDPM). Poly(DEDPM) prepared by the action of 2 consists of 95 % five‐membered rings, that is, poly(cyclopent‐1‐enevinylene)s, and 5 % of six‐membered rings, that is, poly(cyclohex‐1‐ene‐3‐methylidene)s. The polymerization proceeds in a nonliving manner and results in polyenes with broad polydispersities (1.9≦PDI≦2.3). Supported analogues of 2 were prepared by immobilization on hydroxymethyl‐Merrifield resin and a monolithic support derived from ring‐opening‐metathesis polymerization (ROMP). Catalyst loadings of 1 and 2.5 %, respectively, were obtained. Both supported versions of 2 showed excellent reactivity. With 0.24–2 % of the supported catalysts, yields in RCM and ROCM were in the range of 76–100 %. Leaching of ruthenium was low and resulted in Ru contaminations of the products of less than 0.000014 % (0.14 ppm).
Gaseous H5P2O8− Ions: A Theoretical and Experimental Study on the Hydrolysis and Synthesis of Diphosphate Ion
Authors: Pepi Federico , Ricci Andreina , Rosi Marzio , Di Stefano Marco 
Published: October 2004

AbstractThe structure and reactivity of gaseous H5P2O8− ions obtained from the chemical ionization (CI) of an H4P2O7/H2O mixture and from electrospray ionization (ESI) of CH3CN/H2O/H4P2O7 solutions were investigated by Fourier transform ion cyclotron (FTICR) and triple quadrupole mass spectrometry. Theoretical calculations performed at the B3LYP/6‐31+G* level of theory and collisionally activated dissociation (CAD) mass spectrometric results allowed the ionic population obtained in the CI conditions to be structurally characterized as a mixture of gaseous [H3P2O7⋅⋅⋅H2O]−, [H3PO4⋅⋅⋅H2PO4]−, and [PO3⋅⋅⋅H3PO4⋅⋅⋅H2O]− clusters. The energy profile emerging from theoretical calculations affords insight into the mechanism of diphosphate ion hydrolysis and synthesis.
Hydrogen Bonding of Water Confined in Mesoporous Silica MCM‐41 and SBA‐15 Studied by 1H Solid‐State NMR
Authors: Grünberg Bob , Emmler Thomas , Gedat Egbert , Shenderovich Ilja , Findenegg Gerhard H. , Limbach Hans‐Heinrich , Buntkowsky Gerd 
Published: October 2004

AbstractThe adsorption of water in two mesoporous silica materials with cylindrical pores of uniform diameter, MCM‐41 and SBA‐15, was studied by 1H MAS (MAS=magic angle spinning) and static solid‐state NMR spectroscopy. All observed hydrogen atoms are either surface SiOH groups or hydrogen‐bonded water molecules. Unlike MCM‐41, some strongly bound water molecules exist at the inner surfaces of SBA‐15 that are assigned to surface defects. At higher filling levels, a further difference between MCM‐41 and SBA‐15 is observed. Water molecules in MCM‐41 exhibit a bimodal line distribution of chemical shifts, with one peak at the position of inner‐bulk water, and the second peak at the position of water molecules in fast exchange with surface SiOH groups. In SBA‐15, a single line is observed that shifts continuously as the pore filling is increased. This result is attributed to a different pore‐filling mechanism for the two silica materials. In MCM‐41, due to its small pore diameter (3.3 nm), pore filling by pore condensation (axial‐pore‐filling mode) occurs at a low relative pressure, corresponding roughly to a single adsorbed monolayer. For SBA‐15, owing to its larger pore diameter (8 nm), a gradual increase in the thickness of the adsorbed layer (radial‐pore‐filling mode) prevails until pore condensation takes place at a higher level of pore filling.