bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical pharmacokinetics of a novel HIV‐1 attachment inhibitor BMS‐378806 and prediction of its human pharmacokinetics
Authors: Yang Zheng , Zadjura Lisa , D'Arienzo Celia , Marino Anthony , Santone Kenneth , Klunk Lewis , Greene Douglas , Lin Pin‐Fang , Colonno Richard , Wang Tao , Meanwell Nicholas , Hansel Steven 
Published: September 2005

AbstractBMS‐378806 is a prototype of novel HIV attachment inhibitors that block the gp120 and CD4 interaction, the first step of HIV‐1 entry into cells. The present work investigated the pharmacokinetics of BMS‐378806 in rats, dogs and monkeys and assessed its in vitro permeability and metabolism. BMS‐378806 exhibited species‐dependent oral bioavailability which was 19%–24% in rats and monkeys and 77% in dogs. In rats and monkeys, absorption was prolonged, with an apparent terminal half‐life of 2.1 and 6.5 h, respectively. In rats, linear pharmacokinetics was observed between i.v. doses of 1 and 5 mg/kg and between p.o. doses of 5 and 25 mg/kg. The total body clearance was intermediate in rats and low in dogs and monkeys. The steady‐state volume of distribution was moderate (0.4–0.6 l/kg), contributing to a short half‐life (0.3–1.2 h) after i.v. dosing. Studies in bile‐duct cannulated rats together with intraportal infusion studies revealed that the renal and hepatic clearance each accounted for 30% and 70% of the total elimination in rats, with the hepatic clearance largely being oxidative metabolism. In vitro, BMS‐378806 was not highly protein bound (44%–73%). The Caco‐2 permeability was modest (51 nm/s) and confounded by P‐glycoprotein mediated efflux transport. Both of these may contribute to the low brain penetration observed in rats (brain/plasma AUC ratio=0.06). In human liver microsomes BMS‐378806 was equally metabolized by cytochrome P450 1A2, 2D6 and 3A4 and did not inhibit major drug‐metabolizing enzymes to a significant extent. Based on in vitro and animal data, a mechanistic approach that factors in absorption and first‐pass metabolism was employed to predict the human oral bioavailability of BMS‐378806 (ca 20%). This, together with the complex Dedrick plot method, was used to simulate human oral profiles and to project an efficacious dose. These study results offer a comprehensive assessment of the developability of BMS‐378806 and provide important guidance to improving absorption and half‐life of future compounds in the series. The current studies also demonstrate the value and approaches of understanding pharmacokinetic properties in the early stage of drug discovery. Copyright © 2005 John Wiley & Sons, Ltd.
Production of a recombinant cholera toxin B subunit‐insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetes
Authors: Yuki Yoshikazu , Hara‐Yakoyama Chisato , Guadiz Abigail A.E. , Udaka Shigezo , Kiyono Hiroshi , Chatterjee Subhendra 
Published: September 2005

AbstractMucosally induced tolerance is an attractive strategy for preventing or reducing autoimmune diseases. Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9–23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion‐expression system. Receptor‐competitive assay showed that the CTB‐insulin peptide binds to GM1 receptor almost equivalent degree as the native form of CTB. Non‐obese diabetes (NOD) mice that spontaneously develop an insulin‐dependent diabetes were nasally immunized with CTB‐insulin peptide (5 µg) for three times. The nasal treatment significantly reduced the development of insulin‐dependent diabetes and peptide specific DTH responses after systemic immunization with the insulin peptide B 9–23(C19S) in CFA. Nasal administration of as high as 50 µg of the peptide alone demonstrated a similar level of the disease inhibition. In contrast, all mice given 5 µg of the insulin peptide alone or 5 µg of insulin peptide with 25 µg of the free form of CTB did not lead to the suppression of diabetes development and DTH responses. Because molecular weight of the insulin peptide is about one tenth of that of the CTB‐insulin peptide, the results demonstrate that the recombinant hybrid of autoantigen and CTB increased its tolerogenic potential for nasal administration by up 100‐fold on molar base of autoantigen peptide. Taken together, nasally‐induced tolerance by administration of the recombinant B.choshinensis‐derived hybrid protein of CTB and autoantigen T cell‐epitope peptide could be useful mucosal immunetherapy for the control of T cell‐mediated autoimmune diseases. © 2005 Wiley Periodicals, Inc.
Structure of a cellulose degrading bacterial community during anaerobic digestion
Authors: O'Sullivan Cathryn A. , Burrell Paul C. , Clarke William P. , Blackall Linda L. 
Published: September 2005

AbstractIt is widely accepted that cellulose is the rate‐limiting substrate in the anaerobic digestion of organic solid wastes and that cellulose solubilisation is largely mediated by surface attached bacteria. However, little is known about the identity or the ecophysiology of cellulolytic microorganisms from landfills and anaerobic digesters. The aim of this study was to investigate an enriched cellulolytic microbial community from an anaerobic batch reactor. Chemical oxygen demand balancing was used to calculate the cellulose solubilisation rate and the degree of cellulose solubilisation. Fluorescence in situ hybridisation (FISH) was used to assess the relative abundance and physical location of three groups of bacteria belonging to the Clostridium lineage of the Firmicutes that have been implicated as the dominant cellulose degraders in this system. Quantitation of the relative abundance using FISH showed that there were changes in the microbial community structure throughout the digestion. However, comparison of these results to the process data reveals that these changes had no impact on the cellulose solubilisation in the reactor. The rate of cellulose solubilisation was approximately stable for much of the digestion despite changes in the cellulolytic population. The solubilisation rate appears to be most strongly affected by the rate of surface area colonisation and the biofilm architecture with the accepted model of first order kinetics due to surface area limitation applying only when the cellulose particles are fully covered with a thin layer of cells. © 2005 Wiley Periodicals, Inc.
Role of cranberry juice on molecular‐scale surface characteristics and adhesion behavior of Escherichia coli
Authors: Liu Yatao , Black Matthew A. , Caron Lizabeth , Camesano Terri A. 
Published: September 2005

AbstractCranberry juice has long been believed to benefit the prevention and treatment of urinary tract infections (UTIs). As the first step in the development of infection, bacterial adhesion is of great research interest, yet few studies have addressed molecular level adhesion in this context. P‐fimbriated Escherichia coli play a major role in the development of a serious type of UTI, acute pyelonephritis. Experiments were conducted to investigate the molecular‐scale effects of cranberry juice on two E. coli strains: HB101, which has no fimbriae, and the mutant HB101pDC1 which expresses P‐fimbriae. Atomic force microscopy (AFM) was used to investigate both bacterial surface characteristics and adhesion forces between a probe surface (silicon nitride) and the bacteria, providing a direct evaluation of bacterial adhesion and interaction forces. Cranberry juice affected bacterial surface polymer and adhesion behavior after a short exposure period (<3 h). Cranberry juice affected the P‐fimbriated bacteria by decreasing the adhesion forces between the bacterium and tip and by altering the conformation of the surface macromolecules on E. coli HB101pDC1. The equilibrium length of polymer (P‐fimbriae) on this bacterium decreased from ∼148 to ∼48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains. Our results demonstrate molecular‐level changes in the surfaces of P‐fimbriated E. coli upon exposure to neutralized cranberry juice. © 2005 Wiley Periodicals, Inc.
Protective effects of long term dietary restriction on swimming exercise‐induced oxidative stress in the liver, heart and kidney of rat
Authors: Aydin Cenk , Ince Erdal , Koparan Senay , Cangul I. Taci , Naziroglu Mustafa , Ak Fusun 
Published: September 2005

AbstractIn this study, we evaluated the hypothesis that long term dietary restriction would have beneficial effects on the oxidative stress and antioxidant enzyme systems in liver, heart and kidney in adult male rats undergoing different intensities of swimming exercise. Sixty male, Sprague–Dawley rats were assigned as either dietary restricted on every other week day (DR) or fed ad libitum (AL) groups, and each group was further subdivided into sedentary, endurance swimming exercise training (submaximal exercise) and exhaustive swimming exercise (maximal exercise) groups. Animals in the submaximal exercise group swam 5 days/week for 8 weeks, while maximal exercise was performed as an acute bout of exercise.In parallel with the increase in the intensity of the exercise, the degree of lipid peroxidation and protein oxidation were increased in both the DR and AL groups; however the rate of increase was lower in the DR group. Reduced glutathione (GSH), glutathione peroxidase (GSH‐Px) and glutathione reductase (GR) enzyme activities were lower in the DR group than in the AL group. In parallel with the increase in exercise intensity, GSH and GR enzyme activities decreased, whereas an increase was observed in GSH‐Px enzyme activity.In conclusion, the comparison between the DR and AL groups with the three swimming exercise conditions shows that the DR group is greatly protected against different swimming exercise‐induced oxidative stress compared with the AL group. Copyright © 2005 John Wiley & Sons, Ltd.
Transcatheter atrial septal defect closure: Modified balloon sizing technique to avoid overstretching the defect and oversizing the Amplatzer septal occluder
Authors: Carlson Karina M. , Justino Henri , O'Brien Richard E. , Dimas V. Vivian , Leonard Glenn T. , Pignatelli Ricardo H. , Mullins Charles E. , Smith E. O'Brian , Grifka Ronald G. 
Published: September 2005

AbstractThe objective of this study was to evaluate a new technique of sizing atrial septal defects (ASDs) for transcatheter device closure. ASD closure using the Amplatzer septal occluder (ASO) device is commonly performed. Complications, including arrhythmias, pericardial effusions, and perforations, may be related to oversizing ASDs and choosing larger devices. Two methods were used to size ASDs using a compliant balloon. In some patients, the balloon was inflated until a waist was visible [(+)waist]; in others, only until no shunting was demonstrable by echocardiogram [echo; (−)waist]. The device was selected and implanted using standard procedure and echo guidance. One hundred seventeen patients underwent secundum ASD closure with an ASO device. There were 43 patients in the (−)waist group and 74 in the (+)waist group. All devices were implanted successfully. The initial echo ASD diameter was larger in the (−)waist group compared to the (+)waist group (P = 0.01). There was a smaller difference between the initial echo and balloon‐sized ASD diameters in the (−)waist group (P < 0.02). ASO device size implanted (in mm greater than echo ASD diameter) was smaller in the (−)waist group (P < 0.01). There were 0/43 complications in the (−)waist group and 5/74 in the (+)waist group. The complete closure rate was the same in both groups. Sizing an ASD by inflating a compliant balloon just until shunting is eliminated, and not until a waist is visible, results in less overstretching of the ASD and selection of a smaller ASO device, achieving similar closure rates and potentially fewer complications. Catheter Cardiovasc Interv 2005;. © 2005 Wiley‐Liss, Inc.
Non‐negativity constraints for elimination of multiple solutions in fitting of multivariate kinetic models to spectroscopic data
Authors: Jaumot Joaquim , Gemperline Paul J. , Stang Alexandra 
Published: September 2005

AbstractMultiple solutions arise when fitting complicated multi‐step kinetic models to spectroscopic data. For consecutive reactions of the type A→B→C this well‐known ambiguity is due to the presence of multiple equivalent global minima in the response surfaces associated with the non‐linear least squares fitting of rate constants to spectroscopic data. Several methods have been described to overcome the ambiguity when fitting consecutive reactions with univariate data but few attempts to solve the problem have been described for multivariate data. Additionally, for complicated multi‐step reaction schemes there may be several local minima that make selection of the initial parameter guesses difficult. This paper reports a general approach to overcome these types of ambiguities in multivariate kinetic fitting methods using non‐negativity constraints for the determination of the pure component spectra estimated during the model‐fitting process. Under many conditions these constraints reduce or eliminate entirely the incorrect local minima. The effectiveness and reliability of the new constraints were tested with several simulated and real data sets. Copyright © 2005 John Wiley & Sons, Ltd.
Novel Multichiral Diols and Diamines by Highly Stereoselective Pinacol Coupling of Planar Chiral [2.2]Paracyclophane Derivatives
Authors: Sergeeva Elena V. , Rozenberg Valeria I. , Antonov Dmitrii Yu. , Vorontsov Evgenii V. , Starikova Zoya A. , Fedyanin Ivan V. , Hopf Henning 
Published: September 2005

AbstractThe TiCl4/Zn‐mediated intermolecular pinacol coupling of the planar chiral carbonyl compounds [2.2]paracyclophane‐4‐carbaldehyde, 4‐acetyl[2.2]paracyclophane (ketone) and the four regioisomeric 5‐, 7‐, 12‐ and 13‐methoxy[2.2]paracyclophane‐4‐carbaldehydes as well as the pTosOH–Zn/Cu‐promoted coupling of their N‐substituted imines is described. Coupling of the enantiomerically pure substrates (most of carbonyl compounds and all imines) occurs stereoselectively giving rise to diastereomerically pure 1,2‐diols and 1,2‐diamines. Racemic aldehydes and ketone react with different degrees of stereoselectivity (depending on the substituents in certain positions) and produce one to three diastereomers. 7‐Methoxy[2.2]paracyclophane‐4‐carbaldehyde undergoes a tandem pinacol coupling–pinacol rearrangement to yield bis‐(7‐methoxy[2.2]paracyclophane‐4‐yl)acetaldehyde. Coupling of the racemic imines produces a mixture of single racemic D,L‐diamine and single meso‐diamine in each case. The stereoselective formation of the asymmetric centres is governed by the planar chiral [2.2]paracyclophanyl moiety. The techniques elaborated are extended to the intramolecular coupling of [2.2]paracyclophane‐4,13‐dicarbaldehyde and its bis‐N‐phenylimine, resulting in stereoselective formation of the chiral triply‐bridged diol and exclusive formation of the meso‐diamine. X‐Ray investigations of several diols and diamines have been carried out and the structural features of these derivatives are discussed.
Silylenes, Silenes, and Disilenes: Novel Silicon‐Based Reagents for Organic Synthesis?
Authors: Ottosson Henrik , Steel Patrick G. 
Published: September 2005

AbstractSilylenes, silenes, and disilenes are silicon analogues of carbenes and alkenes. Since the first detection and isolation of these species a few decades ago, focus has been given to their fundamental structure and reactivity properties. Recent developments show that the time is set to exploit their unique chemistry in applied areas. Emerging applications in catalysis and stereoselective synthesis point to a new field within synthetic organosilicon chemistry.
Charge and Spin Correlations of a One‐Dimensional Electron Gas on the Continuum
Authors: Casula Michele , Senatore Gaetano 
Published: September 2005

AbstractWe present a variational Monte Carlo study of a model one‐dimensional electron gas on the continuum, with long‐range interaction (1/r decay). At low density, the reduced dimensionality brings about pseudonodes of the many‐body wavefunction, yielding nonergodic behavior of naive Monte Carlo sampling, which affects the evaluation of pair correlations and the related structure factors. The problem is, however, easily solved, and we carefully analyzed the structure factors obtained from an optimal trial function, finding good agreement with the exact predictions for a Luttinger‐like Hamiltonian with an interaction similar to the one used in the present study.
Efficient Evaluation of Nonlocal Pseudopotentials via Euler Exponential Spline Interpolation
Authors: Lee Hee‐Seung , Tuckerman Mark E. , Martyna Glenn J. 
Published: September 2005

AbstractAn Euler exponential spline (EES) based formalism is employed to derive new expressions for the electron–atom nonlocal pseudopotential interaction (NL) in electronic structure calculations performed using a plane wave basis set that can be computed more rapidly than standard techniques. Two methods, one that is evaluated by switching between real and reciprocal space via fast Fourier transforms, and another that is evaluated completely in real space, are described. The reciprocal‐space or g‐space‐based technique, NLEES‐G, scales as NMlogM∼N2logN, where N is the number of electronic orbitals and M is the number of plane waves. The real‐space based technique, NLEES‐R, scales as N2. The latter can potentially be used within a maximally spatially localized orbital method to yield linear scaling, while the former could be employed within a maximally delocalized orbital method to yield NlogN scaling. This behavior is to be contrasted with standard techniques, which scale as N3. The two new approaches are validated using several examples, including solid silicon and liquid water, and demonstrated to be improvements on other, reduced‐order nonlocal techniques. Indeed, the new methods have a low overhead and become more efficient than the standard technique for systems with roughly 20 or more atoms. Both NLEES methods are shown to work stably and efficiently within the Car–Parrinello ab initio molecular dynamics framework, owing to the existence of p−2 continuous derivatives of a pth‐order spline.
Space‐time ring‐TCM codes with CPM based on the decomposed model for transmission over Rayleigh fading channels
Authors: Pereira A. , Carrasco R. A. 
Published: September 2005

AbstractSpace–time (ST) coding is a proved technique for achieving high data rates in 3G mobile systems that combines coding, modulation and multiple transmitters and receivers. A novel algorithm is proposed for ST ring trellis‐coded modulation (ST‐RTCM) systems with continuous‐phase modulation (CPM) when the channel coefficients are known to the receiver. This algorithm is based on the CPM decomposed model, which exploits the memory properties of this modulation method, resulting in a straightforward implementation of joint ST coding and CPM, which is particularly suitable for ring codes. This new scheme is used to investigate the performance of the delay diversity code with CPM over slow Rayleigh fading channels, in particular with MSK which is one of the most widely used modulation methods of continuous phase. Furthermore, a feedback version of delay diversity allowed by the decomposition is tested in 1REC and 1RC systems. This feedback configuration is seen to provide good results for low signal‐to‐noise ratios. Simulations results are also provided for multilevel ST‐RTCM codes that achieve a higher throughput than MSK‐coded systems. Additionally the serial concatenation of an outer Reed–Solomon code with an ST‐RTCM code is shown, this combination further reduces the error probability and achieves even more reliable communications. Copyright © 2005 John Wiley & Sons, Ltd.
Diffuse soft tissue emphysema in anorexia nervosa: A case report
Authors: Lin Liang‐Yu , Kwok Ching‐Fai , Tang Kam‐Tsun , Ho Low‐Tone , Lin Hong‐Da 
Published: September 2005

AbstractObjectiveAnorexia nervosa (AN) is an eating disorder that occurs mainly among young females and its prevalence has increased in recent decades.MethodsWe reported a patient with AN with spontaneous diffuse soft tissue emphysema and bicytopenia, both of which are very rare complications of AN. Our patient, a 20‐year‐old woman, had lost 41.6% of her previous body weight within 9 months. Her body mass index was 10.8 and amenorrhea had persisted for 5 months.ResultsAfter admission, she was diagnosed with AN‐restrictive subtype. She was noted to have crunching sounds in the neck and upper chest wall during hospitalization. A chest X‐ray and chest computed tomography scan both revealed diffuse soft tissue emphysema including subcutaneous emphysema, pneumomediastinum, and pneumoretroperitoneum.DiscussionDiffuse soft tissue emphysema improved gradually and completely resolved on the 21st day of hospitalization. This condition seems to be benign and only a short period of hospitalization is required. © 2005 by Wiley Periodicals, Inc.
Antigen delivery via two molecules on the CD8– dendritic cell subset induces humoral immunity in the absence of conventional “danger”
Authors: Corbett Alexandra J. , Caminschi Irina , McKenzie Brent S. , Brady Jamie L. , Wright Mark D. , Mottram Patricia L. , Hogarth P. Mark , Hodder Anthony N. , Zhan Yifan , Tarlinton David M. , Shortman Ken , Lew Andrew M. 
Published: September 2005

AbstractTargeting antigen to dendritic cells (DC) in vivo might be an effective method of modulating immune responses. Given the functional specializations among DC subsets, we investigated how targeting different receptors on different DC subsets may influence antibody (Ab) production. We show here that targeting FIRE (F4/80‐like receptor) or CIRE (C‐type lectin receptor), two molecules expressed on the surface of immature CD8– DC in the mouse, increases Ab production 100–1000‐fold over a non‐targeted control. This response was equivalent to that achieved with CpG adjuvant. In contrast, targeting CD205, which is primarily expressed on CD8+ DC, did not elicit an Ab response unless an adjuvant was added. Strong Ab responses in FcRγ–/– mice, and with the use of F(ab')2 fragments, confirmed that FIRE and CIRE targeting was due to specific rather than FcR or complement binding. Our findings may reflect differences in the ability of CD8+ and CD8– DC subsets to stimulate immune responses in vivo. Although the consensus view is that Ag presentation on DC in their steady state leads to tolerance, the Ab enhancement from FIRE and CIRE targeting in the apparent absence of any “danger” or inflammatory signal would suggest that targeting certain DC molecules can supplant the need for external adjuvants for eliciting immune responses.