bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed‐dose oral etoposide in patients with solid tumors
Authors: Rocha Lima Caio M. S. , Catapano Carlo V. , Pacheco Daniel , Sherman Carol A. , Oakhill Greg , Mushtaq Chaudhry , Freeman Kimberly D. , Green Mark R. 
Published: May 2004

AbstractBACKGROUNDBased on preclinical findings and on the clinical antitumor efficacy of sequential paclitaxel/topotecan and topotecan/etoposide, the authors sought to define the maximum tolerated doses (MTDs) and dose‐limiting toxicities (DLTs) associated with a sequential combination of paclitaxel, topotecan, and etoposide in patients with solid tumors.METHODSThe MTDs were determined through standard dose escalation in cohorts of three patients. Patients with refractory solid tumors and performance status ≤ 2 were treated with intravenous paclitaxel 50–110 mg/m2 (Day 1), oral topotecan 0.5–2.0 mg/m2 (Days 2–4), and oral etoposide 160 mg/m2 (Days 5–7) during every 21‐day cycle. For dose‐limiting neutropenia, granulocyte–colony‐stimulating factor (G‐CSF) was administered on Day 8 in subsequent cohorts. Blood samples were obtained before treatment during Cycle 1 (Days 1, 2, and 5) for topoisomerase I assessment.RESULTSTwenty‐eight patients received a combined total of 129 cycles. The MTDs were paclitaxel 80 mg/m2, topotecan 1.5 mg/m2, and etoposide 160 mg/m2 without G‐CSF. In minimally pretreated patients, G‐CSF allowed paclitaxel dose escalation to 110 mg/m2. Three patients (11%) had radiologic partial responses, and 4 patients (14%) had stable disease. Day 2 topoisomerase I levels increased by 2–15 times relative to baseline levels in 7 of 14 patients analyzed (50%).CONCLUSIONSThe novel sequential combination that was evaluated generally was well tolerated and active in patients with refractory solid tumors. Based on hematologic DLTs, the authors recommend further evaluation of paclitaxel 110 mg/m2, topotecan 1.5 mg/m2, and etoposide 160 mg/m2 with G‐CSF support in minimally pretreated patients. Cancer 2004. © 2004 American Cancer Society.
Dynamic deactivation for advection‐dominated contaminant transport
Authors: Löhner Rainald , Camelli Fernando 
Published: May 2004

AbstractA simple dynamic deactivation procedure for advection‐dominated contaminant transport is presented. The key idea is to avoid any work in regions where the solution cannot change, i.e. where sources vanish and unknowns do not exhibit any spatial change. Saving factors in CPU of 1: 3–1: 10 are commonly achieved. The procedure is general and simple to implement, and should be applicable to a large number of codes and transport problems. Copyright © 2004 John Wiley & Sons, Ltd.
Photophysical Aspects of Single‐Molecule Detection by Two‐Photon Excitation with Consideration of Sequential Pulsed Illumination
Authors: Niesner R. , Roth W. , Gericke Karl‐Heinz 
Published: May 2004

AbstractAn important goal in single molecule fluorescence correlation spectroscopy is the theoretical simulation of the fluorescence signal stemming from individual molecules and its autocorrelation function. The simulation approaches developed up to now are based exclusively on continuous‐wave (cw) illumination and consequently on cw‐excitation. However, this approximation is no longer valid in the case of two‐photon excitation, for which pulsed illumination is usually employed. We present a novel theoretical model for the simulation of the fluorescence signal of single molecules and its autocorrelation function with consideration of the time dependence of the excitation flux and thus of all illumination‐dependent photoprocesses: two‐photon excitation, induced emission and photobleaching. Further important characteristics of our approach are the consideration of the dependence of the photobleaching rate on illumination and the low intersystem‐crossing rates of the studied coumarins. Moreover, using our approach, we can predict quantitatively the effect of the laser pulse width on the fluorescence signal of a molecule, that is, the contributions of the photobleaching and saturation effects, and thus we can calculate the optimal laser pulse width. The theoretical autocorrelation functions were fitted to the experimental data, and we could ascertain a good agreement between the resulting and the expected parameters. The most important parameter is the photobleaching constant σ, the cross section of the transition Sn←S1, which characterises the photostability of the molecules independent of the experimental conditions. Its value is 1.7×10−23 cm2 for coumarin 153 and 5×10−23 cm2 for coumarin 314.
Dissolution of Crystallites: Surface Energetic Control and Size Effects
Authors: Tang Ruikang , Orme Christine A. , Nancollas George H. 
Published: May 2004

AbstractTraditional understanding of dissolution assumes that the reaction is spontaneous and continues until equilibrium is reached. This paper presents theoretical and experimental data to support a dissolution mechanism that involves the existence of critical conditions for dissolution, in which the reaction is accompanied by the formation of pits and the subsequent displacement of pit steps. The accompanying increase in surface roughness leads to changes in surface energy with losses of crystal mass that are positive rather than negative and the existence of critical dissolution conditions. Critical pits and dissolution steps are verified experimentally and a relationship between the size and rate of displacement of steps is also demonstrated, in which the rate decreases with size and approaches zero at a critical size, r*. These microscopic step dynamics are consistent with the observed size‐effects in bulk dissolution, which cannot be explained using traditional dissolution theories. The observed size effects include self‐inhibition, in which the dissolution rate decreases with extent of reaction, dissolution suppression, and periodic resumption. These interesting dissolution phenomena are only readily displayed when the sizes of dissolving crystallites fall in the same range as the critical size (i.e., within 50r*). It is interesting to note that natural biominerals and many nanoparticles fall into this category, so that their suspensions can be dynamically stabilized without dissolution in undersaturated supporting media. The current research implies that dissolution kinetics cannot be understood well without appealing to fundamental physical concepts about the energetic control of dissolution steps on a molecular level. A new dissolution model for crystallites is introduced systemically.
Comparison of Properties of Aib‐Rich Peptides in Crystal and Solution: A Molecular Dynamics Study
Authors: Yu Haibo , Ramseier Maaike , Bürgi Roland , van Gunsteren Wilfred F. 
Published: May 2004

AbstractIn order to study the differences of the structural properties of Aib‐rich peptides in solution and in the crystalline state, molecular dynamics (MD) simulations of the Aib‐containing peptide II (pBrBz‐(Aib)5‐Leu‐(Aib)2‐OMe) were performed in the crystalline state, starting from two different conformers obtained experimentally by X‐ray diffraction. The structural properties as derived from X‐ray crystallography (e.g., torsional angles and hydrogen bonds) are well‐reproduced in both constant‐volume and constant‐pressure simulations, although the force‐field parameters used result in a too‐high density of the crystals. Through comparison with the results from previous MD and nuclear magnetic resonance (NMR) studies of the very similar peptide I (Z‐(Aib)5‐Leu‐(Aib)2‐OMe) in dimethylsulfoxide (DMSO) solution, it is found that, in the crystal simulation, the conformational distribution of peptide II is much narrower than that in the solution simulation of peptide I. This leads to a significant difference in 3J(HN, HCα) coupling constant values, in agreement with experimental data, whereas the NOE intensities or proton–proton distance bounds appear insensitive to the difference in conformational distribution. For small peptides the differences between their conformational distribution in the crystalline form and in solution may be much larger than for proteins, a fact which should be kept in mind when interpretating molecular properties in the solution state by using X‐ray crystallographic data.
Quantum Dynamics of Gas‐Phase SN2 Reactions
Authors: Schmatz Stefan 
Published: May 2004

AbstractUnderstanding the state‐resolved dynamics of elementary chemical reactions involving polyatomic molecules, such as the well‐known reaction mechanism of nucleophilic bimolecular substitution (SN2), is one of the principal goals in chemistry. In this Review, the progress in the quantum mechanical treatment of SN2 reactions in the gas phase is reviewed. The potential energy profile of this class of reactions is characterized by two relatively deep wells, which correspond to pre‐ and post‐reaction charge–dipole complexes. As a consequence, the complex‐forming reaction is dominated by Feshbach resonances. Calculations in the energetic continuum constitute a major challenge because the high density of resonance states imposes considerable requirements on the convergence and the energetic resolution of the scattering data. However, the effort is rewarding because new insights into the details of multimode quantum dynamics of elementary chemical reactions can be obtained.
Electronic Structure and Chemical Reactivity of Carbon Nanotubes: A Chemist's View
Authors: Joselevich Ernesto 
Published: May 2004

AbstractA qualitative description of the electronic structure of single‐wall carbon nanotubes from a chemical perspective is presented using real‐space orbital representations and traditional concepts of aromaticity, orbital symmetry and frontier orbitals. This unusual view of carbon nanotubes allows us to merge the solid‐state physics description of band structures with the molecular orbitals framework of reaction mechanisms used in organic chemistry and to predict intriguing chemical selectivity based on electronic structure.
Kinetics and Mechanism of the C6H5 + CH3CHO Reaction: Experimental Measurement and Theoretical Prediction of the Reactivity toward Four Molecular Sites
Authors: Choi Y. M. , Park J. , Lin M. C. 
Published: May 2004

AbstractThe kinetics and mechanism of the reaction of C6H5 with CH3CHO have been investigated experimentally and theoretically. The total rate constant for the reaction has been measured by means of the cavity ring‐down spectrometry (CRDS) in the temperature range 299–501 K at pressures covering 20–75 Torr. The overall bimolecular rate constant can be represented by the expression k=(2.8±0.2)×1011 exp[−(700±30)/T] cm3 mol−1 s−1, which is slightly faster than for the analogous C6H5+CH2O reaction determined with the same method in the same temperature range. The reaction mechanism for the C6H5+CH3CHO reaction was also explored with quantum‐chemical calculations at various hybrid density functional theories (DFTs) and using ab initio high‐level composite methods. The theories predict that the reaction may occur by two hydrogen‐abstraction and two addition channels with the aldehydic hydrogen‐abstraction reaction being dominant. The rate constant calculated by the transition state theory for the aldehydic hydrogen‐abstraction reaction is in good agreement with the experimental result after a very small adjustment of the predicted reaction barrier (+0.3 kcal mol−1). Contributions from other product channels are negligible under our experimental conditions. For combustion applications, we have calculated the rate constants for key product channels in the temperature range of 298–2500 K under atmospheric‐pressure conditions; they can be represented by the following expressions in units of cm3 mol−1 s−1: k1,cho=8.8×103 T2.6 exp(−90/T), k2,ch3=6.0×101 T3.3 exp(−950/T), k3a(C6H5COCH3+H)=4.2×105 T0.6 exp(−410/T) and k3b(C6H5CHO+CH3)=6.6×109 T−0.5 exp(−310/T).
Ultrafast Proton‐Coupled Electron‐Transfer Dynamics in Pyrene‐Modified Pyrimidine Nucleosides: Model Studies towards an Understanding of Reductive Electron Transport in DNA
Authors: Raytchev Milen , Mayer Elke , Amann Nicole , Wagenknecht Hans‐Achim , Fiebig Torsten 
Published: May 2004

Abstract5‐(Pyren‐1‐yl)‐2′‐deoxyuridine (PydU) and 5‐(Pyren‐1‐yl)‐2′‐deoxycytidine (PydC) were used as model nucleosides for DNA‐mediated reductive electron transport (ET) in steady‐state fluorescence and femtosecond time‐resolved transient absorption spectroscopy studies. Excitation of the pyrene moiety in PydU and PydC leads to an intramolecular electron transfer that yields the pyrenyl radical cation and the corresponding pyrimidine radical anion (dU.− and dC.−. By comparing the excited state dynamics of PydC and PydU, we derived information about the energy difference between the two pyrimidine radical anion states. To determine the influence of protonation on the rates of photoinduced intramolecular ET, the spectroscopic investigations were performed in acetonitrile, MeCN, and in water at different pH values. The results show a significant difference in the basicity of the generated pyrimidine radical anions and imply an involvement of proton transfer during electron hopping in DNA. Our studies revealed that the radical anion dC.− is being protonated even in basic aqueous solution on a picosecond time scale (or faster). These results suggest that protonation of dC.− may also occur in DNA. In contrast, efficient ET in PydU could only be observed at low pH values (<5). In conclusion, we propose—based on the free energy differences and the different basicities—that only dT.− but not dC.− can participate as an intermediate charge carrier for excess electron migration in DNA.
Electronic gel protein transfer and identification using matrix‐assisted laser desorption/ionization‐mass spectrometry
Authors: Cooper Jonathan W. , Gao Jun , Lee Cheng S. 
Published: May 2004

AbstractAn electronic protein transfer technique is described for achieving the rapid and efficient recovery of sodium dodecyl sulfate (SDS)‐protein complexes from polyacrylamide gels. This process involves the use of small‐dimension capillaries in physical contact with a resolved protein band within the polyacrylamide gel, providing a large potential drop and high electric field strength at the capillary/gel interface. Several factors controlling the electronic protein transfer, including the applied electric field strength, the electrophoresis buffer concentration, and the capillary dimension, are studied to further enhance the use of field‐amplification for sample stacking of extracted SDS‐protein complexes. As a result of sample stacking, the extracted proteins from a 50 ng gel loading are present in a narrow (∼80 nL) and highly concentrated (0.46 mg/mL or 3.3×10−5 M for cytochrome c) solution plug. Three model proteins with molecular mass ranging from 14 kDa (cytochrome c) to 116 kDa (β‐galactosidase) are stained by Coomassie blue and electrophoretically extracted from gels with protein loadings as low as 50 ng. The capillary format of the electronic protein transfer technique allows direct deposition of extracted proteins onto a matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) target. Various matrices and solvent compositions are evaluated for the analysis of extracted and concentrated SDS‐protein complexes using MALDI‐MS. The electronic protein transfer technique, when operated under optimized conditions, is demonstrated for the effective (>70% recovery), speedy (less than 5 min), and sensitive MS identification of gel resolved proteins (as low as 50 ng).
Analysis of the sinusitis nasal lavage fluid proteome using capillary liquid chromatography interfaced to electrospray ionization‐quadrupole time of flight‐ tandem mass spectrometry
Authors: Casado Begona , Pannell Lewis K. , Viglio Simona , Iadarola Paolo , Baraniuk James N. 
Published: May 2004

AbstractThe nasal lavage fluids (NLFs) from four subjects with acute sinusitis were analyzed to investigate the amount of proteins expressed in this pathology at the beginning of the event (day 1) and after 6 days of treatment with antibiotics and a nasal steroid spray. The protein identification was performed with capillary liquid chromatography‐electrospray‐quadrupole time of flight‐(LC‐ESI‐Q‐TOF)‐mass spectrometry. The samples collected on the first day contained high‐abundant plasma proteins, such as albumin and immunoglobulins, glandular serous cell proteins (lysozyme, lactoferrin, and polymeric immunoglobulin receptor), epithelial keratins, and inflammatory cell proteins (myeloperoxidase, IL‐16, and IL‐17E). After six days of therapy, the complexity of the proteome was reduced to plasma proteins and lysozyme with no inflammatory markers. The presence of hemoglobin, however, suggested that significant squamous metaplasia with breaches in the epithelial barrier, or nasal steroid‐related bleeding, had occurred. The proteomic approach presented here allowed us to identify, in the high complexity of acute sinusitis nasal secretions, the proteins that respond to a pharmacological treatment and that could be suitable as markers of this pathology.
Chiral cyclodextrin‐modified microemulsion electrokinetic chromatography
Authors: Mertzman Melissa D. , Foley Joe P. 
Published: May 2004

AbstractCyclodextrin (CD)‐modified microemulsion electrokinetic chromatography (MEEKC) or CD‐MEEKC has not previously been applied to the area of chiral separations. Herein, the results of investigations of various microemulsions with CD additives are presented. Two different microemulsions are explored: an ethyl acetate sodium dodecyl sulfate microemulsion, and a chiral dodecoxycarbonylvaline (DDCV) microemulsion. Each microemulsion is paired separately with a neutral CD (hydroxypropyl‐β‐CD) and an anionic CD (sulfated‐β‐CD). In addition, the chiral DDCV microemulsion is investigated in both the R‐ and S‐ form. By varying simple parameters such as buffer system, applied voltage, surfactant enantiomer, and type of cyclodextrin, dramatic improvements in the chiral separations were noted. Resolution was found to be highly dependent on buffer identity and concentration, and somewhat dependent on whether the CDs used were randomly or highly sulfated. Under optimized conditions, the resolution ranged from 0.8 to 4.8, with plate counts ranging from 4000 to 26 000. Additionally, S‐ and R‐levetiracetam, which had never before been enantioseparated via capillary electrophoresis (CE) methodologies, were separated in less than 8 min, with a resolution of 1.1.
Capillary electrophoresis of cationic random coil peptide standards: Effect of anionic ion‐pairing reagents and comparison with reversed‐phase chromatography
Authors: Popa Traian V. , Mant Colin T. , Hodges Robert S. 
Published: May 2004

AbstractThe present study compares a charge/hydrophobicity capillary electrophoresis (CE) approach to reversed‐phase high‐performance liquid chromatography (RP‐HPLC) for the separation of three series of four synthetic, random coil peptide standards. Each series has peptides of the same positive charge (+1, +2 and +3 series) and length but differing in hydrophobicity. Complete resolution of the 12 peptides was achieved via a novel CE approach: a capillary zone electrophoresis (CZE) mode effected a separation of identically charged peptides; within each charged group of peptides, the addition of perfluorinated acid anionic ion‐pairing reagents allowed resolution of the peptides through a mechanism based on peptide hydrophobicity which we have termed ioninteraction (II)‐CZE. The peak capacity and peptide resolution of this CE approach was superior to that of RP‐HPLC and stresses an important role for CE for peptide/proteomic applications.
Single‐isomer sulfated α‐cyclodextrins for capillary electrophoresis. Part 2. Hexakis(6‐O‐sulfo)‐α‐cyclodextrin: Synthesis, analytical characterization, and initial screening tests
Authors: Li Shulan , Vigh Gyula 
Published: May 2004

AbstractThe second member of the family of single‐isomer sulfated α‐cyclodextrins, the sodium salt of hexakis(6‐O‐sulfo)‐α‐cyclodextrin (HxS), has been synthesized, analytically characterized, and used as the resolving agent for the capillary electrophoretic separation of the enantiomers of nonionic, weak‐acid and weak‐base analytes present in our initial screening kit. HxS interacted less strongly with many of the analytes tested than the larger‐ring analogs, heptakis(6‐O‐sulfo)‐β‐cyclodextrin (HS) and octakis(6‐O‐sulfo)‐γ‐cyclodextrin (OS). For some of the analytes, the separation selectivities obtained with HxS were complementary to those observed with hexakis(2,3‐di‐O‐acetyl‐6‐O‐sulfo)‐α‐cyclodextrin (HxDAS), HS, and OS. For all analytes, the effective mobilities and separation selectivities as a function of the background electrolyte concentration of HxS followed the trends that were found for HxDAS, HS, and OS.
Determination of dissociation constants for a heparin‐binding domain of amyloid precursor protein and heparins or heparan sulfate by affinity capillary electrophoresis
Authors: McKeon Jocelyn , Holland Lisa A. 
Published: May 2004

AbstractDynamic affinity capillary electrophoresis (ACE) was used for determining the binding constants between heparin‐like glycosaminoglycans and the (96–110) heparin‐binding domain of amyloid precursor protein (APP). The migration time shift of the (96–110) APP peptide was monitored as the concentration of heparin was increased in the background electrolyte. The compounds investigated included low‐molecular‐weight heparin, porcine mucosa heparin, and heparan sulfate. Change in mobility as a function of glycosaminoglycan concentration was plotted using both linear regression (Scatchard analysis) and nonlinear regression. Dissociation constants (Kd) were determined and compared for both sets of analyses with the low‐molecular‐weight heparin giving the most reproducible results and best fit with a Kd value of 3.9 μM.
Upper flammability limits of some organosilicon compounds
Authors: Hshieh Fu‐Yu , Hirsch David B. , Williams James H. , Beeson Harold D. 
Published: May 2004

AbstractThis paper reports the upper flammability limits of 26 organosilicon compounds commonly used in the silicone industry and investigates the correlation between the upper flammability limit and the net heat of combustion. An empirical equation has been developed to predict the upper flammability limit of organosilicon compounds using the net heat of combustion. Copyright © 2004 John Wiley & Sons, Ltd.
Adaptive mesh refinement and coarsening for aerodynamic flow simulations
Authors: Scalabrin Leonardo Costa , Azevedo João Luiz F. 
Published: May 2004

AbstractA new mesh refinement technique for unstructured grids is discussed. The new technique presents the important advantage of maintaining the original grid skewness, thanks to the capability of handling hanging nodes. The paper also presents an interpretation of MacCormack's method in an unstructured grid context. Results for a transonic convergent–divergent nozzle, for a convergent nozzle with a supersonic entrance and for transonic flow over a NACA 0012 airfoil are presented and discussed. Copyright © 2004 John Wiley & Sons, Ltd.