bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus
Authors: Furie Richard , Stohl William , Ginzler Ellen M , Becker Michael , Mishra Nilamadhab , Chatham Winn , Merrill Joan T , Weinstein Arthur , McCune W Joseph , Zhong John , Cai Wendy , Freimuth William ,   the Belimumab Study Group
Published: September 2008

Abstract
Introduction
This trial evaluated the safety, biologic activity, and pharmacokinetics of belimumab, a fully human monoclonal antibody that inhibits the biologic activity of the soluble form of the essential B-cell survival factor B-lymphocyte stimulator (BLyS) in patients with systemic lupus erythematosus (SLE).

Methods
Seventy patients with mild-to-moderate SLE were enrolled in a phase I, double-blind, randomized study and treated with placebo (n = 13) or belimumab (n = 57) at four different doses (1.0, 4.0, 10, and 20 mg/kg) as a single infusion or two infusions 21 days apart. Patients were followed for 84 to 105 days to assess adverse events, pharmacokinetics, peripheral blood B-cell counts, serology, and SLE disease activity. Data from the study were summarized using descriptive statistics. χ2 type tests were used to analyze discrete variables. The Kruskal-Wallis test, the Wilcoxon test, and the analysis of covariance were used to analyze the continuous variables, as appropriate. The analysis was performed on all randomized patients who received study agent.

Results
The incidences of adverse events and laboratory abnormalities were similar among the belimumab and placebo groups. Belimumab pharmacokinetics were linear across the 1.0 to 20 mg/kg dose range. Long terminal elimination half-life (8.5 to 14.1 days), slow clearance (7 ml/day per kg), and small volume of distribution (69 to 112 ml/kg) were consistent with a fully human antibody. Significant reductions in median percentages of CD20+ B cells were observed in patients treated with a single dose of belimumab versus placebo (day 42: P = 0.0042; and day 84: P = 0.0036) and in patients treated with two doses of belimumab versus placebo (day 105: P = 0.0305). SLE disease activity did not change after one or two doses of belimumab.

Conclusions
Belimumab was well tolerated and reduced peripheral B-cell levels in SLE patients. These data support further studies of belimumab in autoimmune disorders.

Trial Registration
NCT00657007 [clinicaltrials.gov].
Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm
Authors: Futier Emmanuel , Constantin Jean-Michel , Combaret Lydie , Mosoni Laurent , Roszyk Laurence , Sapin Vincent , Attaix Didier , Jung Boris , Jaber Samir , Bazin Jean-Etienne 
Published: September 2008

Abstract
Introduction
Controlled mechanical ventilation (CMV) induces profound modifications of diaphragm protein metabolism, including muscle atrophy and severe ventilator-induced diaphragmatic dysfunction. Diaphragmatic modifications could be decreased by spontaneous breathing. We hypothesized that mechanical ventilation in pressure support ventilation (PSV), which preserves diaphragm muscle activity, would limit diaphragmatic protein catabolism.

Methods
Forty-two adult Sprague-Dawley rats were included in this prospective randomized animal study. After intraperitoneal anesthesia, animals were randomly assigned to the control group or to receive 6 or 18 hours of CMV or PSV. After sacrifice and incubation with 14C-phenylalanine, in vitro proteolysis and protein synthesis were measured on the costal region of the diaphragm. We also measured myofibrillar protein carbonyl levels and the activity of 20S proteasome and tripeptidylpeptidase II.

Results
Compared with control animals, diaphragmatic protein catabolism was significantly increased after 18 hours of CMV (33%, P = 0.0001) but not after 6 hours. CMV also decreased protein synthesis by 50% (P = 0.0012) after 6 hours and by 65% (P < 0.0001) after 18 hours of mechanical ventilation. Both 20S proteasome activity levels were increased by CMV. Compared with CMV, 6 and 18 hours of PSV showed no significant increase in proteolysis. PSV did not significantly increase protein synthesis versus controls. Both CMV and PSV increased protein carbonyl levels after 18 hours of mechanical ventilation from +63% (P < 0.001) and +82% (P < 0.0005), respectively.

Conclusions
PSV is efficient at reducing mechanical ventilation-induced proteolysis and inhibition of protein synthesis without modifications in the level of oxidative injury compared with continuous mechanical ventilation. PSV could be an interesting alternative to limit ventilator-induced diaphragmatic dysfunction.
Influence of enrollment sequence effect on observed outcomes in the ADDRESS and PROWESS studies of drotrecogin alfa (activated) in patients with severe sepsis
Authors: Laterre Pierre-François , Macias William L , Janes Jonathan , Williams Mark D , Nelson David R , Girbes Amand RJ , Dhainaut Jean-François , Abraham Edward 
Published: September 2008

Abstract
Introduction
We performed a study to determine whether an enrollment sequence effect noted in the PROWESS (recombinant human activated Protein C Worldwide Evaluation in Severe Sepsis) trial exists in the ADDRESS (Administration of Drotrecogin Alfa [Activated] [DrotAA] in Early Stage Severe Sepsis) trial.

Methods
We evaluated prospectively defined subgroups from two large phase 3 clinical trials: ADDRESS, which included 516 sites in 34 countries, and PROWESS, which included 164 sites in 11 countries. ADDRESS consisted of patients with severe sepsis at low risk of death not indicated for treatment with DrotAA. PROWESS consisted of patients with severe sepsis with one or more organ dysfunctions. DrotAA (24 μg/kg per hour) or placebo was infused for 96 hours.

Results
In ADDRESS and PROWESS, there was a statistically significant interaction between the DrotAA treatment effect and the sequence in which patients were enrolled. In both trials, higher mortality was associated with DrotAA use in the subgroup of patients enrolled first at study sites. Compared with placebo, PROWESS mortality was lower with DrotAA treatment for the second and subsequent patients enrolled, whereas in ADDRESS, mortality remained higher for the second patient enrolled but thereafter was lower for DrotAA-treated patients. Comparison of patients enrolled first with subsequent patients enrolled indicated that the characteristics of patients changed. Subsequently enrolled patients were treated earlier, were less likely to suffer nonserious bleeds (ADDRESS), and experienced fewer protocol violations (PROWESS).

Conclusions
Analyses suggest that an enrollment sequence effect was present in the ADDRESS and PROWESS trials. Analysis of this effect on outcomes suggests that it is most apparent in patients at lower risk of death. In PROWESS, this effect appeared to be associated with a reduction of the DrotAA treatment effect for the first patients enrolled at each site. In ADDRESS, this effect may have contributed to early termination of the study. The finding of an enrollment sequence effect in two separate trials suggests that trial designs, site selection and training, data collection and monitoring, and statistical analysis plans may need to be adjusted for these potentially confounding events.

Trial Registration
ADDRESS trial registration number: NCT00568737. PROWESS was completed before trial registration was required.
Functional expression of IgA receptor FcαRI on human platelets
Authors: Qian Kun , Xie Fenglong , Gibson Andrew W , Edberg Jeffrey C , Kimberly Robert P , Wu Jianming 
Published: September 2008

AbstractFcαRI (CD89) is a human IgA FcR expressed on cells of myeloid lineage such as neutrophils, monocytes, tissue macrophages, eosinophils, and subpopulations of dendritic cells. FcαRI mediates cell activation through Src family kinases and downstream tyrosine-based phosphorylation pathways. However, the role of IgA and the expression and role of its cognate receptor FcαRI (CD89) in platelet activation are undefined. In the current study, we demonstrate that human platelets express FcαRI mRNAs and proteins. Furthermore, we show that the platelet FcαRI is associated with the FcR γ-chain, and cross-linking of FcαRI leads to Syk phosphorylation. Clustering of FcαRI induces pre-mRNA splicing and protein production of tissue factor and IL-1β, suggesting novel roles for human platelet FcαRI and serum IgA in thrombosis and inflammation.
Molecular Basis for Transition-State Stabilization in Catalytic Antibodies
Authors: Tsumuraya Takeshi , Fujii Ikuo 
Published: September 2008

Abstract
Antibodies elicited against rationally designed transition-state analogs catalyze a large number of reactions, including many that cannot be achieved by standard chemical methods. This account describes a detailed investigation of the molecular mechanism of catalysis in catalytic antibodies. We have investigated the biochemical properties within a panel of six hydrolytic catalytic antibodies elicited against a phosphonate transition-state analog. The transition-state analyses (kcat⁄kuncat versus Km⁄Ki) displayed a linear relationship with five antibodies, 6D9, 8D11, 4D5, 3G6, and 9C10, which have homologous primary amino acid sequences, while antibody 7C8 deviates from the linear relationship. These results suggest that the five antibodies catalyze the hydrolysis by the same reaction mechanism of transition-state stabilization and that catalytic factors other than transition-state stabilization are involved for antibody 7C8. The structure of 6D9 Fab with the transition-state analog (TSA) has been solved, showing that 6D9 binds the phosphonate of TSA by forming one hydrogen bond with HisL27d. The kinetic, structural, and thermodynamic analyses of 6D9 indicate that this antibody provides an efficient catalyst by transition-state stabilization through the hydrogen bond with HisL27d and the destabilization of the substrate. Although catalytic antibodies are still much inferior to natural enzymes in their catalytic efficiency, several aspects including the mechanism of enzyme catalysts can be faithfully mimicked. Therefore, the molecular mechanism of catalytic antibodies might provide useful insights to understanding the catalysis in enzymes.
Catalytic Behavior of Cationic Hydridoruthenium(II) Complex, [RuH(NH3)(PMe3)4]+, in H2-Hydrogenation and Transfer Hydrogenation of Imines
Authors: Kayaki Yoshihito , Ikeda Hibiki , Tsurumaki Jun-ichirou , Shimizu Isao , Yamamoto Akio 
Published: September 2008

Abstract
Catalytic hydrogenation under H2 and transfer hydrogenation of imines by secondary alcohols with hydridoruthenium complexes bearing PMe3 and PPh3 ligands have been examined. A cationic hydridoruthenium complex, cis-[RuH(NH3)(PMe3)4]PF6 (2), derived from cis-[RuH2(PMe3)4] (1) and NH4PF6, showed higher catalytic activity for H2-hydrogenation of N-benzylideneaniline than neutral complexes such as 1 and cis-[RuClH(PMe3)4] (6). The effectiveness of cationic hydridoruthenium species for the catalytic H2-hydrogenation of benzylideneaniline was also demonstrated by a marked increase in the yield of N-benzylaniline on treatment of 6 with AgPF6. The cationic complex 2 was applicable to catalytic transfer hydrogenation of imines with secondary alcohols even in the absence of a base. Isotope labeling experiments using deuterated alcohols revealed that the hydrogen atom bound to the α-carbon of the donor alcohol was transferred exclusively to the imine carbon and alcoholic OD was transferred to the imine nitrogen. A rapid exchange between the alcoholic proton and the hydrido ligand of 2 was also confirmed by NMR investigation using (CH3)2CHOD. On the basis of the experimental results the mechanisms of the H2-hydrogenation and transfer hydrogenation are discussed.
Gangliosides’ Inhibitory Effects on NAD Glycohydrolase: Estimating the Solvation Effect in the Physiological Environment
Authors: Ueno-Noto Kaori , Hara-Yokoyama Miki , Takano Keiko 
Published: September 2008

Abstract
The solvation effect was considered in order to interpret the causative factors of the differences in gangliosides’ inhibitory effects on CD38, an enzyme nicotinamide adenine dinucleotide (NAD) glycohydrolase, as well as the mechanisms by which the gangliosides recognize CD38, in the biological system. We applied the two-layered our own N-layered integrated molecular orbital and molecular mechanics (ONIOM) method as well as the supermolecule method to a large solvated system. For comparison, the conductor-like screening model (COSMO) was applied to the same system. The orbital energy of the highest occupied molecular orbital (HOMO) was correlated with the strength of the gangliosides’ inhibitory effect in both the supermolecule and ONIOM methods; this agrees with our previous results in the gas phase. Solvation only slightly affected both the structures of tandem sialic acid residues themselves and the energy profiles of HOMOs of gangliosides. These results support the previously proposed recognition mechanism, in which CD38 is likely to recognize the two phosphate groups in the substrate, NAD, as well as the two carboxyl groups in gangliosides’ tandem sialic acid residues.
Thermodynamics of Zinc(II) Complexes with N′1,N′2-Dihydroxy-N1,N2-dipyridin-2-ylethanediamidediimide in the Gas Phase
Authors: Zabardasti Abedien , Kakanejadifard Ali , Amani Saeid , Salehnassaje Maryam 
Published: September 2008

Abstract
Ab initio and density functional calculations were used to study the coordination and thermodynamic properties of mononuclear complexes of dimethylglyoxime (H2M), diaminoglyoxime (H2A), and (1Z,2Z)-N′1,N′2-dihydroxy-N1,N2-dipyridin-2-ylethanediamidediimide (H2L) as well as dinuclear complexes of H2L with zinc(II) at B3LYP/6-31G(d), B3LYP/6-31+G(d), and B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) computational levels. Theoretical calculation shows that unusual O,O-coordination is a stable model for coordination of H2L to zinc(II) in the gas phase.
Effect of Internal Branching on Numbers of Monosubstituted Alkanes as Three-Dimensional Structures and as Graphs
Authors: Fujita Shinsaku 
Published: September 2008

Abstract
Itemized numbers of achiral and/or chiral monosubstituted alkanes (MSAs) as three-dimensional structures have been obtained by means of a newly developed method based on Fujita’s proligand method (S. Fujita, Theor. Chem. Acc.2005, 113, 73; 2005, 113, 80; 2006, 115, 37), where the itemization with respect to internal branching has been embodied by employing branching indicators (BIs), i.e., q for quaternary carbons, t for tertiary carbons, s for secondary carbons, and p for primary carbons. Each of the numbers appears as the coefficient of a branching monomial qnqtntsnspnpxk, which is contained in a generating function to characterize MSAs having nq quaternary carbons, nt tertiary carbons, ns secondary carbons, and nq quaternary carbons (k=nq+nt+ns+np). By following Fujita’s proligand method, functional equations for recursive calculations have been obtained to treat respective cases, where previous approaches without considering BIs have been extended so as to incorporate BIs with no violation of consistency. The resulting functional equations have been used to obtain generating functions which give the numbers of achiral MSAs, chiral MSAs, total (achiral and chiral) MSAs. They have been compared with the corresponding numbers of MSAs as graphs. Thereby, difference between stereoisomers (3D structures) and constitutional isomers (graphs) has been discussed on a quantitative basis.
Molecular Structure Optimization and Molecular Dynamics Using Hamiltonian Algorithm: Structure of Benzodiazepine Minor Tranquilizers—Towards Non-Empirical Drug Design—
Authors: Teramae Hiroyuki , Ohtawara Kazushige , Ishimoto Takayoshi , Nagashima Umpei 
Published: September 2008

Abstract
We have studied the molecular dynamics of the benzodiazepine and thienodiazepine minor tranquilizers using a Hamiltonian Algorithm (HA) combined with ab initio molecular orbital methods. The HA utilizes classical dynamics for optimization of the complicated systems. We show that the HA gives an effective search of the potential energy surfaces and we can find an energy minimum even if we start from another energy local minimum. The conformers of these minor tranquilizers are calculated after computation of the molecular dynamics. Relations between electronic states and strength of tranquilizers are studied for about 17 species of benzodiazepines and thienodiazepines which are sold in the Japanese market as minor tranquilizers. The orbital energy levels of the next highest occupied molecular orbital (next-HOMO or HOMO−1) are found to be strongly related to the strength of the tranquilizers. The simple structure–activity relationship is obtained by considering just one-electron properties, i.e., the molecular orbital energies.
Spectrophotometric Determination of Gold after Separation and Preconcentration with a Solid-Phase Extraction Method
Authors: Sorouraddin Mohammad-Hossein , Saadati Masoud 
Published: September 2008

Abstract
A simple, sensitive, and inexpensive method for separation and preconcentration of gold ions from aqueous solutions prior to its spectrophotometric determination is reported. The proposed method includes two procedures. In the first one, sodium 8-aminoquinoline-5-azobenzene-4′-sulfonate (SPAQ) was immobilized directly on an alumina column which adsorbed gold ions from aqueous solutions. Then, AuIII was desorbed by HCl solution, and the absorbance of the alkaline solution in the presence of a cationic surfactant, cetyltrimethylammonium bromide (CTMAB), was measured at 611 nm. In the second procedure, Au–SPAQ complex in the presence of CTMAB in alkaline media was passed through the column containing alumina (washed with nitric acid and neutralized by washing with distilled water). The complex was then desorbed with ethanol, and the absorbance was measured immediately at 611 nm. The proposed methods were applied successfully to the determination of gold in Azerbaijan ores. The relative standard deviations for five replicate determinations of 0.2 μg mL−1 AuIII for the first and second procedures were 3.01% and 2.66%, and the corresponding limits of detection were 1.37 and 3.70 μg L−1, respectively.
Substituent and Solvent Effects on Square-Planar–Tetrahedral Equilibria of Bis[4-(arylimino)pentan-2-onato]nickel(II) and Bis[1-aryl-3-(phenylimino)butan-1-onato]nickel(II) Complexes
Authors: Mori Yukie , Shirase Hitoshi , Fukuda Yutaka 
Published: September 2008

Abstract
Nickel(II) bis(Schiff base) complexes, NiL2 (1a–1f) and NiL′2 (2a–2e) (where L = 4-(arylimino)pentan-2-onate and L′ = 1-aryl-3-(phenylimino)butan-1-onate), exist in an equilibrium of square-planar (Sp) and tetrahedral (Td) forms in non-coordinating solvents. The Td form is more stabilized in polar solvents such as CH2Cl2 than in non-polar solvents such as toluene. Thermodynamic data were determined from temperature-dependent 1H NMR contact shift. It is suggested for 1a–1f that the oxygen atoms in Td form interact with solvent such as chloroform via hydrogen bonding. With increase in electron-donating ability of the substituents on aryl groups, the Td form becomes more favored. The free energy change roughly correlates with Hammet’s σp value. The UV–vis–NIR spectra indicated that the ligand field strength increases with the electron-donating ability of the substituents in both the Sp and Td forms. Results of DFT calculation suggest that the observed substituent effect may result from small perturbation of the metal–ligand bonding character.
Synthesis and Fluorescent Properties of a Chiral Conjugated Polymer Based on (S)-2,2′-Binaphtho-20-crown-6
Authors: Huang Hui , Miao Qian , Kang Yixiong , Huang Xiaobo , Xu Jinqian , Cheng Yixiang 
Published: September 2008

Abstract
Linear conjugated polymer was obtained by the polymerization of 2,3-dibutoxy-1,4-diethynylnaphthalene (M-1) and (S)-5,5′-dibromo-6,6′-dibutyl-2,2′-binaphtho-20-crown-6 (S-M-2) via Pd-catalyzed Sonogashira reaction. The conjugated polymer shows strong green-blue fluorescence due to the extended π-electronic structure between the chiral repeating unit (S)-6,6′-dibutyl-2,2′-binaphtho-20-crown-6 and the conjugated linker 2,3-dibutoxynaphthyl group via acetylene bridge. The responsive properties of the chiral polymer on K+, Pb2+, Hg2+, and AsIII were investigated by fluorescent spectra. The results show that Hg2+ and AsIII can cause effective fluorescent quenching of the polymer, whereas, K+ and Pb2+ do not produce obvious changes in the polymer fluorescence. The obvious fluorescent influence shows that the 2,2′-binaphtho-20-crown-6 moiety plays an important role in fluorescent recognition for Hg2+ and AsIII due to the effective photoinduced electron transfer (PET) and charge transfer (PCT) between the conjugated polymer backbone and receptor species.
Crystal Structures, Degree of Charge Transfer, and Non-Linear Optical Characteristics of Intramolecular Charge-Transfer Compounds: Indoline-Substituted Tricyanoquinodimethanes
Authors: Murata Tsuyoshi , Saito Gunzi , Nishimura Kazukuni , Chong Chin-Hong , Makihara Masaru , Honda Genki , Enomoto Yuichiro , Khasanov Salavat , Yamochi Hideki , Otsuka Akihiro , Kamada Kenji , Ohta Koji , Kawamata Jun 
Published: September 2008

Abstract
The substituent effect on the degree of intramolecular charge transfer (δ) and optical properties of donor–π–acceptor compounds comprised of 1,3,3-trimethyl-2-methyleneindoline (I1) and substituted 7,8,8-tricyanoquinodimethane (=2-(4-cyanomethylene-2,5-cyclohexadienylidene)malononitrile, 3CNQ-R, R = substituent groups) moieties were investigated (I1–3CNQ-R). In the crystal structures, I1–3CNQ-R molecules stacked on indoline and/or 3CNQ-R moieties in a head-to-tail manner to cancel their dipole moments and established segregated or mixed stack columnar motifs. The δ values of I1–3CNQ-R molecules in solid and solution states were estimated using the bond length ratio in the crystal structures, molecular orbital calculation, and the solvatochromic shift of intramolecular charge-transfer absorption, respectively, and showed significant and reasonable dependences on substituents of the 3CNQ moiety. Structural analysis revealed that molecular conformation and planarity affect the δ values of I1–3CNQ-R molecules. Molecular orbital calculations revealed that molecular (hyper)polarizabilities can be modulated by tuning δ. I1–3CNQ-R exhibited a solvatochromic shift, and the ground state changed from neutral (δ≤0.5) in less-polar solvents to ionic (δ≥0.5) in polar solvents. Two-photon absorption properties of I1–3CNQ-R showed a significant substituent effect and indicated that δ is a fundamental parameter for modulating non-linear optical properties.
Effects of Added CO2 and H2 on the Direct Decomposition of NO over BaMnO3-Based Perovskite Oxide
Authors: Iwakuni Hideharu , Shinmyou Yusuke , Yano Hiroaki , Goto Kazuya , Matsumoto Hiroshige , Ishihara Tatsumi 
Published: September 2008

Abstract
N2 yield on Ba0.8La0.2Mn0.8Mg0.2O3 decreased from 70% to 30% on the addition of 1% CO2, which is a much larger negative effect than that seen with O2. The CO2 negative effects are not permanent and this may result from the inhibition of NO adsorption. Co-feeding of H2 as a reductant is effective for increasing NO conversion. This suggests that the catalyst surface was covered with strongly adsorbed nitrate or nitride species which formed by adsorption of NO on oxygen formed by the decomposition of NO, and the removal of this surface species might be the most important step for the NO decomposition reaction. Co-feeding of H2 is also effective for increasing the NO decomposition activity in the presence of CO2. The reaction mechanism was studied by IR measurements which also revealed that the surface of the catalyst was covered with strongly bound nitrate species (NO3−). The addition of H2 to the reaction mixture is effective for NO3− removal and so accelerates the NO decomposition under coexistence of CO2.