bluuebunny/crossref_metadata_2025 huggingface dataset:
Group contribution prediction of surface charge density profiles for COSMO‐RS(Ol)
Authors: Mu Tiancheng , Rarey Jürgen , Gmehling Jürgen
Published: October 2007

A new method for predicting the surface charge density distribution (σ profile) and cavity volume of molecules based on group contributions was developed. The original σ profiles used for the regression were obtained using Gaussian 03 B3LYP/6‐311G(d,p). In total 1363 σ profiles were used for the regression of group parameters. Group definitions are identical to those used previously for boiling point estimation. Original and estimated σ profiles were used to predict activity coefficients at infinite dilution and VLE data of binary systems using the COSMO‐RS(Ol) model. The results were compared with the experimental data stored in the Dortmund Data Bank. In many cases the results were of comparable accuracy. However, for a few compounds, poor results were obtained, in particular for conjugated components like nitrobenzenes. The method offers a fast and reliable generation of σ profiles to be used with COSMO‐RS(Ol) within its range of applicability. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Reproductive parameters of wild female Rhinopithecus roxellana
Authors: Qi Xiao‐Guang , Li Bao‐Guo , Ji Wei‐Hong
Published: October 2007

On the basis on 6 years of observation, we estimated the reproductive parameters of a Golden snub‐nosed monkey (Rhinopithecus roxellana) group in the Qinling Mountains, China. We observed 88 births in 47 females from 2001 to 2006. Two methods were used to calculate the birthrate. The first method is based on the number of births observed in a year, giving 0.49±0.07 (mean±SD), and the second method is based on the female‐years of observation, giving 0.49±0.17 births per female per year in this troop. The mean interbirth interval is 21.88±6.01 months (mean±SD). The mortality of infant born between 2002 and 2005 was 22.4%. The interbirth intervals of females that had lost an infant before the age of 6 months were significantly shorter than that of females whose infants survived for more than 6 months. A female usually gives birth once every 2 years if the previous offspring survives to a weaning age of 5–6 months, or will give birth in the next year if the previous young dies before reaching an age of 6 months. Births were significantly concentrated during March to May of each year. The mean birth date was on April 14, median was April 12; and the standard deviation was 13.98 days. Birth peak occurs 6–7 months after mating peak. From observations on 15 individuals that gave birth for the first time, we concluded that the wild female Golden snub‐nosed monkeys in Qinling Mountains start giving birth at an age of 5 or 6 years. We suggest that the seasonal reproductive pattern is an adaptive response to the availability of seasonal food. Our results are consistent with the hypothesis that these reproductive characteristics are a result of adaptation to the seasonality of mountain climate and food resources. Am. J. Primatol. 70:311–319, 2008. © 2007 Wiley‐Liss, Inc.
Metallkatalysierte enantioselektive Allylierungen in der asymmetrischen Synthese
Authors: Lu Zhan , Ma Shengming
Published: October 2007

Durch metallkatalysierte enantioselektive Allylierungen, die unter Substitution von Allylmetall‐Zwischenstufen mit zahlreichen Nucleophilen oder als allylische SN2′‐Substitution verlaufen, werden in Gegenwart ausgewählter Kombinationen aus Metallen und chiralen Liganden C‐H‐, C‐C‐, C‐O‐, C‐N‐, C‐S‐ und andere Bindungen mit sehr hoher asymmetrischer Induktion geknüpft. Die Reaktionen sind mit einer Vielzahl funktioneller Gruppen vereinbar und wurden erfolgreich in der Synthese vieler Naturstoffe und neuer chiraler Verbindungen verwendet.
Dual‐mode control with neural network based inverse model for a steel pickling process
Authors: Thitiyasook P. , Kittisupakorn P. , Hussain M. A.
Published: October 2007

This article describes a novel implementation of the dual‐mode (DM) control utilizing a neural network inverse model on a multivariable process (a steel pickling process). This process is highly nonlinear with variable‐interaction, and is multivariable in nature, hence an accurately nonlinear model is required to provide acceptable control. The requirement of a true analytical inverse can be avoided when neural network models are used; they have the ability to approximate both the forward and the inverse system dynamics. Various changes in the open‐loop dynamics are performed before implementation of the inverse neural network modeling technique. DM control based on neural network inverse model strategy is used to design the controllers to control concentration and pH of the process, which is guaranteed to remove steady‐state offset in the controlled variables to obtain the maximum reaction rate and to comply with limits imposed by legislation. The robustness of the proposed DM control is investigated with respect to changes in disturbances and model mismatch. Comparisons are also made with the conventional inverse neural network controller (NNDIC) and other conventional controller proportional‐integral (PI). Simulation results show the superiority of the DM controller in the cases involving disturbance and model mismatch, while the conventional controller gives better results in the nominal case. Copyright © 2007 Curtin University of Technology and John Wiley & Sons, Ltd.
Utilization of emulsion polymer for preparing bagasse fibers polymer–cement composites
Authors: Ismail M. R. , Youssef H. A. , Ali Magdy A. M. , Zahran A. H. , Afifi M. S.
Published: October 2007

Sugarcane‐bagasse fiber–polymer cement composites were prepared using three lattices namely, styrene butadiene, vinyl ester, and styrene acrylic. The lattices percentages ranged between 3 and 21% from the weight of the mixture. The pressed samples were irradiated at different irradiation doses by using electron beam (EB) accelerator. Comparative studies have been made for physicomechanical properties of unirradiated and irradiated samples. The results indicated that the flexural strength, modulus of elasticity, and impact toughness of the composites increase with the increasing polymer content up to 9.9 and 15% of styrene butadiene, vinyl ester, and acrylic styrene, and then decrease. It was also observed that the maximum values of flexural strength and modulus of elasticity obtained at EB‐irradiation dose 45, 40, and 25 kGy for styrene butadiene, acrylic ester, and vinyl ester, respectively. The impact strength of the composites did not significantly improve above 10 kGy. The average values of hardness of irradiated composites were higher than that those of unirradiated and control composites. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Effects of hot‐air aging and dynamic fatigue on the structure and dynamic viscoelastic properties of unfilled natural rubber vulcanizates
Authors: Zhang Ping , Shi Xinyan , Li Junge , Yu Guangshui , Zhao Shugao
Published: October 2007

The effects of hot‐air aging and dynamic tensile fatigue on the network structure and dynamic viscoelastic properties of unfilled natural rubber (NR) vulcanizates were investigated with magnetic resonance crosslink density spectrometry, Fourier transform infrared spectroscopy/attenuated total reflection (FTIR–ATR), and dynamic mechanical analysis. The results showed that there was a carbonyl weak absorption peak at 1723 cm−1 in the FTIR–ATR spectra of unfilled NR vulcanizates after hot‐air aging; The crosslink density decreased continuously as the aging time increased. The dynamic modulus of an aged specimen declined considerably, and the value of tan δ after 72 h of aging greatly increased. There was a large difference in the FTIR–ATR spectra of unfilled NR vulcanizates before and after tensile fatigue. The peaks at 1597, 1415, and 1015 cm−1 increased concurrently with the tensile fatigue time. Initial analysis suggested that structures such as conjugated dienes appeared in the network structure. The modulus declined sharply, whereas the value of tan δ increased noticeably, after tensile fatigue. The effects of hot‐air aging and tensile fatigue on the crosslink density and FTIR–ATR spectra of unfilled NR vulcanizates were different, but both affected the viscoelastic properties dramatically. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Stability of poly(N‐propargylamide)s under ultraviolet irradiation
Authors: Deng Jianping , Li Lei , Wang Jianmin , Feng Guo , Yang Wantai
Published: October 2007

This article investigates the photostability of poly(N‐propargylamide)s under different conditions, on the basis of which application research for this class of highly functional polymers can be performed. With helical polymer 1 [monomer: CCCH2NHCOCH(C2H5)2] taken as a representative, some affecting factors, including the ultraviolet (UV)‐light intensity, presence of oxygen, far‐UV and near‐UV light, and temperature, were investigated. It was found that increasing the UV‐light intensity accelerated the degradation of polymer 1. When oxygen was present, it also facilitated the degradation. Far‐UV light rather than near‐UV light played a predominant role in initiating the degradation of polymer main chains. Elevating the temperature of the polymer solution during UV irradiation made the degradation accelerate. Storing the polymer under weak UV light, in the absence of oxygen, and at a low temperature was favorable for keeping the polymer stable. These findings are important not only from a scientific point of view but especially for developing practical applications of this type of polymer on the basis of its photodegradability. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Rheumatoid arthritis fibroblast‐like synoviocytes express BCMA and are stimulated by APRIL
Authors: Nagatani Katsuya , Itoh Kenji , Nakajima Kyoichi , Kuroki Hirohumi , Katsuragawa Yozo , Mochizuki Makoto , Aotsuka Shinichi , Mimori Akio
Published: October 2007

Objective

Fibroblast‐like synoviocytes (FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the variety of stimulating effects of APRIL and its specific effect on FLS in the affected RA synovium.

Methods

Synovium and serum samples were obtained from patients with RA, patients with osteoarthritis (OA), and healthy subjects. Soluble APRIL proteins were assayed by enzyme‐linked immunosorbent assay. The relative gene expression of APRIL, BCMA, interleukin‐6 (IL‐6), tumor necrosis factor α (TNFα), IL‐1β, and RANKL was assessed in RA and OA FLS by polymerase chain reaction. Effects of APRIL on the production of proinflammatory cytokines and RANKL in RA FLS were investigated by flow cytometry and with the use of a BCMA‐Fc fusion protein.

Results

A significantly higher level of soluble APRIL was detected in RA serum compared with normal serum. Among the 3 receptors of APRIL tested, RA FLS expressed only BCMA, whereas OA FLS expressed none of the receptors. APRIL stimulated RA FLS, but not OA FLS, to produce IL‐6, TNFα, IL‐1β, and APRIL itself. In addition, APRIL increased RA FLS expression of RANKL and also enhanced progression of the cell cycle of RA FLS. Neutralization of APRIL by the BCMA‐Fc fusion protein attenuated all of these stimulating effects of APRIL on RA FLS.

Conclusion

RA FLS are stimulated by APRIL and express the APRIL receptor BCMA. These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA.
Development and characterization of a fusion protein between thermally responsive elastin‐like polypeptide and interleukin‐1 receptor antagonist: Sustained release of a local antiinflammatory therapeutic
Authors: Shamji Mohammed F. , Betre Helawe , Kraus Virginia B. , Chen Jun , Chilkoti Ashutosh , Pichika Rajeswari , Masuda Koichi , Setton Lori A.
Published: October 2007

Objective

Interleukin‐1 receptor antagonist (IL‐1Ra) has been evaluated for the intraarticular treatment of osteoarthritis. Such administration of proteins may have limited utility because of their rapid clearance and short half‐life in the joint. The fusion of a drug to elastin‐like polypeptides (ELPs) promotes the formation of aggregating particles that form a “drug depot” at physiologic temperatures, a phenomenon intended to prolong the presence of the drug. The purpose of this study was to develop an injectable drug depot composed of IL‐1Ra and ELP domains and to evaluate the properties and bioactivity of the recombinant ELP‐IL‐1Ra fusion protein.

Methods

Fusion proteins between IL‐1Ra and 2 distinct sequences and molecular weights of ELP were overexpressed in Escherichia coli. Environmental sensitivity was demonstrated by turbidity and dynamic light scattering as a function of temperature. IL‐1Ra domain activity was evaluated by surface plasmon resonance, and in vitro antagonism of IL‐1–mediated lymphocyte and thymocyte proliferation, as well as IL‐1–induced tumor necrosis factor α (TNFα) expression and matrix metalloproteinase 3 (MMP‐3) and ADAMTS‐4 messenger RNA expression in human intervertebral disc fibrochondrocytes. IL‐1Ra immunoreactivity was assessed before and after proteolytic degradation of the ELP partner.

Results

Both fusion proteins underwent supramolecular aggregation at subphysiologic temperatures and slowly resolubilized at 37°C. Interaction with IL‐1 receptor was slower in association but equivalent in dissociation as compared with the commercial antagonist. Anti–IL‐1 activity was demonstrated by inhibition of lymphocyte and thymocyte proliferation and by decreased TNFα expression and ADAMTS‐4 and MMP‐3 transcription by fibrochondrocytes. ELP domain proteolysis liberated a peptide of comparable size and immunoreactivity as the commercial IL‐1Ra. This peptide was more bioactive against lymphocyte proliferation, nearly equivalent to the commercial antagonist.

Conclusion

The ELP‐IL‐1Ra fusion protein proved to retain the characteristic ELP inverse phase‐transitioning behavior as well as the bioactivity of the IL‐1Ra domain. This technology represents a novel drug carrier designed to prolong the presence of bioactive peptides following intraarticular delivery.
Misdiagnosis of a chylous cyst as chest wall gouty tophus: A case of true pseudogout
Authors: Adhikesavan Leena G. , Ayoub William T. , Schumacher H. Ralph
Published: October 2007

A patient referred to us for recurrent chest wall gouty tophus, but who was determined to actually have a chylous cyst, is described herein. Chylous cysts of the neck or chest wall can be caused by thoracic duct injury. Chyle contains 4–40 gm/liter of lipids, mostly triglycerides, and these can form birefringent crystals upon drying, leading to a false diagnosis of gout.
The nuclear autoantigen CENP‐B displays cytokine‐like activities toward vascular smooth muscle cells
Authors: Robitaille Geneviève , Hénault Jill , Christin Marie‐Soleil , Senécal Jean‐Luc , Raymond Yves
Published: October 2007

Objective

A growing number of intracellular autoantigenic polypeptides have been found to play a second biologic role when they are present in the extracellular medium. We undertook this study to determine whether the CENP‐B nuclear autoantigen could be added to this set of bifunctional molecules.

Methods

Purified CENP‐B or CENP‐B released from apoptotic cells was tested for surface binding to a number of human cell types by cell‐based enzyme‐linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. The biologic effects of CENP‐B on the migration, interleukin secretion, and signaling pathways of its specific target cells were evaluated.

Results

CENP‐B was found to bind specifically to the surface of human pulmonary artery smooth muscle cells (SMCs) and not to fibroblasts or endothelial cells (ECs). Furthermore, CENP‐B bound preferentially to SMCs of the contractile type rather than to SMCs of the synthetic type. Binding of CENP‐B to SMCs stimulated their migration during in vitro wound healing assays, as well as their secretion of interleukins 6 and 8. The mechanism by which CENP‐B mediated these effects involved the focal adhesion kinase, Src, ERK‐1/2, and p38 MAPK pathways. Finally, CENP‐B released from apoptotic ECs was found to bind to SMCs, thus indicating a plausible in vivo source of extracellular CENP‐B.

Conclusion

These novel biologic roles of the nuclear autoantigen CENP‐B open up a new perspective for studying the pathogenic role of anti–CENP‐B autoantibodies.
Association between friction and wear in diarthrodial joints lacking lubricin
Authors: Jay Gregory D. , Torres Jahn R. , Rhee David K. , Helminen Heikki J. , Hytinnen Mika M. , Cha Chung‐Ja , Elsaid Khaled , Kim Kyung‐Suk , Cui Yajun , Warman Matthew L.
Published: October 2007

Objective

The glycoprotein lubricin (encoded by the gene Prg4) is secreted by surface chondrocytes and synovial cells, and has been shown to reduce friction in vitro. In contrast to man‐made bearings, mammalian diarthrodial joints must endogenously produce friction‐reducing agents. This study was undertaken to investigate whether friction is associated with wear.

Methods

The lubricating ability of synovial fluid (SF) samples from humans with genetic lubricin deficiency was tested in vitro. The coefficient of friction in the knee joints of normal and lubricin‐null mice was measured ex vivo; these joints were also studied by light and electron microscopy. Atomic force microscopy was used to image and measure how lubricin reduces friction in vitro.

Results

SF lacking lubricin failed to reduce friction in the boundary mode. Joints of lubricin‐null mice showed early wear and higher friction than joints from their wild‐type counterparts. Lubricin self‐organized and reduced the work of adhesion between apposing asperities.

Conclusion

These data show that friction is coupled with wear at the cartilage surface in vivo. They imply that acquired lubricin degradation occurring in inflammatory joint diseases predisposes the cartilage to damage. Lastly, they suggest that lubricin, or similar biomolecules, will have applications in man‐made devices in which reducing friction is essential.
Microparticles stimulate the synthesis of prostaglandin E2 via induction of cyclooxygenase 2 and microsomal prostaglandin E synthase 1
Authors: Jüngel Astrid , Distler Oliver , Schulze‐Horsel Ursula , Huber Lars C. , Ha Huy Riem , Simmen Beat , Kalden Joachim R. , Pisetsky David S. , Gay Steffen , Distler Jörg H. W.
Published: October 2007

Objective

Microparticles are small vesicles that are released from activated or dying cells and that occur abundantly in the synovial fluid of patients with rheumatoid arthritis (RA). The goal of these studies was to elucidate the mechanisms by which microparticles activate synovial fibroblasts to express a proinflammatory phenotype.

Methods

Microparticles from monocytes and T cells were isolated by differential centrifugation. Synovial fibroblasts were cocultured with increasing numbers of microparticles. Gene expression was analyzed by real‐time polymerase chain reaction and confirmed by Western blotting and enzyme immunoassay. Arachidonic acid labeled with tritium was used to study the transport of biologically active lipids by microparticles. The roles of NF‐κB and activator protein 1 (AP‐1) signaling were analyzed with electrophoretic mobility shift assay and transfection with small interfering RNA and IκB expression vectors.

Results

Microparticles strongly induced the synthesis of cyclooxygenase 2 (COX‐2), microsomal prostaglandin E synthase 1 (mPGES‐1), and prostaglandin E2 (PGE2). In contrast, no up‐regulation of COX‐1, mPGES‐2, cytosolic PGES, or phospholipase A2 was observed. The induction of PGE2 was blocked by selective inhibition of COX‐2. Microparticles activated NF‐κB, AP‐1, p38, and JNK signaling in synovial fibroblasts. Inhibition of NF‐κB, AP‐1, and JNK signaling reduced the stimulatory effects. Arachidonic acid was transported from leukocytes to fibroblasts by microparticles. Arachidonic acid derived from microparticles was converted to PGE2 by synovial fibroblasts.

Conclusion

These results demonstrate that microparticles up‐regulate the production of PGE2 in synovial fibroblasts by inducing COX‐2 and mPGES‐1. These data provide evidence for a novel mechanism by which microparticles may contribute to inflammation and pain in RA.
Gene expression profiling of peripheral blood from patients with untreated new‐onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome
Authors: Fall Ndate , Barnes Michael , Thornton Sherry , Luyrink Lorie , Olson Judyann , Ilowite Norman T. , Gottlieb Beth S. , Griffin Thomas , Sherry David D. , Thompson Susan , Glass David N. , Colbert Robert A. , Grom Alexei A.
Published: October 2007

Objective

Systemic juvenile idiopathic arthritis (JIA) is frequently associated with the development of macrophage activation syndrome. This study was undertaken to better understand the relationship between systemic JIA and macrophage activation syndrome.

Methods

Gene expression profiles were examined in 17 patients with untreated new‐onset systemic JIA, 5 of whom showed evidence of subclinical macrophage activation syndrome (of whom 2 eventually developed overt macrophage activation syndrome). Peripheral blood mononuclear cells (PBMCs) were separated on Ficoll gradients, and purified RNA was analyzed using Affymetrix GeneChip expression arrays. A fraction of the PBMCs were used for flow cytometry to define the cellular composition of the samples.

Results

Two hundred twenty‐five differentially expressed genes (P < 0.05) that distinguished patients with systemic JIA from healthy controls (n = 30) were identified. Clustering analysis indicated that expression patterns correlated with serum ferritin levels. Three main clusters distinguished systemic JIA patients with highly elevated ferritin levels (including those with subclinical macrophage activation syndrome) from those with normal or only moderately elevated ferritin levels. The first cluster comprised genes involved in the synthesis of hemoglobins and structural proteins of erythrocytes. This transcriptional profile was consistent with immature nucleated red blood cells, likely reflective of high red blood cell turnover. Also included were transcripts indicating immature granulocytes. The second cluster was enriched for genes involved in cell cycle regulation. The third cluster was enriched for genes involved in innate immune responses, including those involved in the negative regulation of Toll‐like receptor/interleukin‐1 receptor–triggered inflammatory cascades and markers of the alternative pathway of macrophage differentiation. Additional differentially expressed genes of interest were those involved in the cytolytic pathway, including SH2D1A and Rab27a.

Conclusion

These data indicate that gene expression profiling can be a useful tool for identifying early macrophage activation syndrome in patients with systemic JIA.
Deficiency of the type I interferon receptor protects mice from experimental lupus
Authors: Nacionales Dina C. , Kelly‐Scumpia Kindra M. , Lee Pui Y. , Weinstein Jason S. , Lyons Robert , Sobel Eric , Satoh Minoru , Reeves Westley H.
Published: October 2007

Objective

Systemic lupus erythematosus (SLE) is diagnosed according to a spectrum of clinical manifestations and autoantibodies associated with abnormal expression of type I interferon (IFN‐I)–stimulated genes (ISGs). The role of IFN‐I in the pathogenesis of SLE remains uncertain, partly due to the lack of suitable animal models. The objective of this study was to examine the role of IFN‐I signaling in the pathogenesis of murine lupus induced by 2,6,10,14‐tetramethylpentadecane (TMPD).

Methods

IFN‐I receptor–deficient (IFNAR−/−) 129Sv mice and wild‐type (WT) 129Sv control mice were treated intraperitoneally with TMPD. The expression of ISGs was measured by real‐time polymerase chain reaction. Autoantibody production was evaluated by immunofluorescence and enzyme‐linked immunosorbent assay. Proteinuria and renal glomerular cellularity were measured and renal immune complexes were examined by immunofluorescence.

Results

Increased ISG expression was observed in the peripheral blood of TMPD‐treated WT mice, but not in the peripheral blood of TMPD‐treated IFNAR−/− mice. TMPD did not induce lupus‐specific autoantibodies (anti‐RNP, anti‐Sm, anti–double‐stranded DNA) in IFNAR−/− mice, whereas 129Sv controls developed these specificities. Although glomerular immune complexes were present in IFNAR−/− mice, proteinuria and glomerular hypercellularity did not develop, whereas these features of glomerulonephritis were found in the TMPD‐treated WT controls. The clinical and serologic manifestations observed in TMPD‐treated mice were strongly dependent on IFNAR signaling, which is consistent with the association of increased expression of ISGs with lupus‐specific autoantibodies and nephritis in humans.

Conclusion

Similar to its proposed role in human SLE, signaling via the IFNAR is central to the pathogenesis of autoantibodies and glomerulonephritis in TMPD‐induced lupus. This lupus model is the first animal model shown to recapitulate the “interferon signature” in peripheral blood.
Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: A randomized controlled trial
Authors: Jüni Peter , Reichenbach Stephan , Trelle Sven , Tschannen Beatrice , Wandel Simon , Jordi Beat , Züllig Maya , Guetg Reto , Jörg Häuselmann Hans , Schwarz Hans , Theiler Robert , Ziswiler Hans Rudolf , Dieppe Paul A. , Villiger Peter M. , Egger Matthias
Published: October 2007

Objective

To compare the efficacy and safety of intraarticular hylan and 2 hyaluronic acids (HAs) in osteoarthritis (OA) of the knee.

Methods

This was a multicenter, patient‐blind, randomized controlled trial in 660 patients with symptomatic knee OA. Patients were randomly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations: a high molecular weight cross‐linked hylan, a non–cross‐linked medium molecular weight HA of avian origin, or a non–cross‐linked low molecular weight HA of bacterial origin. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 6 months. Secondary outcome measures included local adverse events (effusions or flares) in injected knees. During months 7–12, patients were offered a second cycle of viscosupplementation.

Results

Pain relief was similar in all 3 groups. The difference in changes between baseline and 6 months between hylan and the combined HAs was 0.1 on the WOMAC pain score (95% confidence interval [95% CI] −0.2, 0.3). No relevant differences were observed in any of the secondary efficacy outcomes, and stratified analyses provided no evidence for differences in effects across different patient groups. There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle (difference 2.2% [95% CI −2.4, 6.7]), and this trend became more pronounced during the second cycle (difference 6.4% [95% CI 0.6, 12.2]).

Conclusion

We found no evidence for a difference in efficacy between hylan and HAs. In view of its higher costs and potential for more local adverse events, we see no rationale for the continued use of hylan in patients with knee OA.
Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus
Authors: Lee Pui Y. , Li Yi , Richards Hanno B. , Chan Fay S. , Zhuang Haoyang , Narain Sonali , Butfiloski Edward J. , Sobel Eric S. , Reeves Westley H. , Segal Mark S.
Published: October 2007

Objective

The premature atherosclerosis seen in patients with systemic lupus erythematosus (SLE) is not explained by traditional risk factors. SLE disease activity, such as renal involvement and presence of autoantibodies, is associated with elevated serum levels of type I interferon (IFN‐I), a family of cytokines with potent antiviral and antiproliferative effects. This study was undertaken to test the hypothesis that elevated IFN‐I levels could lead to endothelial dysfunction, a surrogate for cardiovascular disease, by causing a reduction in the number of endothelial progenitor cells (EPCs), bone marrow–derived cells that participate in endothelial repair.

Methods

EPCs were enumerated in the peripheral blood of SLE patients (n = 70) and healthy controls (n = 31), using a colony‐forming assay. Serum IFN‐I levels were quantified by real‐time polymerase chain reaction measurement of the expression of the IFN‐I–inducible gene MX1. Endothelial function was determined by peripheral arterial plethysmography.

Results

SLE patients had markedly reduced levels of EPC colony‐forming units compared with controls (median 5.7/ml peripheral blood [interquartile range 1.9–12.8] versus 28.5/ml peripheral blood [14.7–47.3]; P < 0.0001), and the depletion of EPCs was more dramatic in patients with elevated levels of IFN‐I. Stepwise multiple regression analysis showed that MX1 expression and serum levels of C‐reactive protein were independently associated with the reduction of EPCs. Importantly, high IFN‐I levels were associated with impaired endothelial function in patients with SLE.

Conclusion

These data support the novel hypothesis that depletion of EPCs caused by excessive IFN‐I may be linked to endothelial dysfunction and increased cardiovascular risk in SLE.
Histopathologic changes at “synovio–entheseal complexes” suggesting a novel mechanism for synovitis in osteoarthritis and spondylarthritis
Authors: Benjamin Michael , McGonagle Dennis
Published: October 2007

Objective

To determine the extent to which different entheses form part of a “synovio–entheseal complex” (SEC) and whether such SECs are commonly associated with the presence of inflammatory cells and evidence of enthesis microdamage.

Methods

Specimens from 49 cadaveric entheses were processed for histologic study, and all soft tissue components of the entheses or enthesis organs were examined. To exclude articular cartilage degeneration as a triggering factor for synovitis, the selected entheses included 17 that were not immediately adjacent to such cartilage.

Results

An SEC was present at 82% of entheses. These included 47% of the attachments not adjacent to articular cartilage, where the synovium was that of bursae or tendon sheaths. One or more of a wide variety of degenerative changes were noted on the soft tissue side of every enthesis; the most common changes were cell clustering and/or fissuring (in 76% of entheses). Synovial villus formation or inflammatory cell infiltration was seen in 85% of entheses, and in 73% of attachments there were also inflammatory cells in the enthesis organ itself. The changes included synovial invasion (pannus formation) of the enthesis.

Conclusion

Entheses are frequently juxtaposed to synovium, thus forming SECs. They are also often associated with both degenerative and inflammatory changes, and the latter may involve the immediately adjacent synovium. These findings suggest a novel mechanism by which synovitis could develop in both degenerative joint disease and spondylarthritis.
Sugarcane ethanol production in Brazil: an expansion model sensitive to socioeconomic and environmental concerns
Authors: Sparovek Gerd , Berndes Göran , Egeskog Andrea , de Freitas Flavio Luiz Mazzaro , Gustafsson Stina , Hansson Julia
Published: October 2007

Brazilian agriculture is characteristically dynamic; land and production resources have a skewed ownership distribution; and agricultural production is essential for small holders of rural poor regions. Also, the main agricultural land use is composed of pastures where extensive livestock production prevails. Because of increasing demand Brazil is expected to expand its sugarcane‐based ethanol production. Addressing concerns about social and environmental impacts of such an expansion requires careful consideration of the complexity of Brazilian agriculture in general and specific local conditions in particular. This perspective outlines an expansion model for sugarcane ethanol production that is sensitive to socioeconomic and environmental concerns. Through integration with the prevailing land use, the model avoids the usual displacement of extensive livestock production to remote regions, causing leakage effects with deforestation and promotes milk and beef cattle intensification and investment opportunities for local society. The expansion model is feasible at current market conditions and should have good prospects for complying with sustainability criteria within various certification schemes presently under development. A case study, developed in the Pontal do Paranapanema region (state of São Paulo, Brazil) illustrates the model in agrarian reform settlements. © 2007 Society of Chemical Industry and John Wiley & Sons, Ltd
Continuum molecular electrostatics, salt effects, and counterion binding—A review of the Poisson–Boltzmann theory and its modifications
Authors: Grochowski Paweł , Trylska Joanna
Published: October 2007

This work is a review of the Poisson–Boltzmann (PB) continuum electrostatics theory and its modifications, with a focus on salt effects and counterion binding. The PB model is one of the mesoscopic theories that describes the electrostatic potential and equilibrium distribution of mobile ions around molecules in solution. It serves as a tool to characterize electrostatic properties of molecules, counterion association, electrostatic contributions to solvation, and molecular binding free energies. We focus on general formulations which can be applied to large molecules of arbitrary shape in all‐atomic representation, including highly charged biomolecules such as nucleic acids. These molecules present a challenge for theoretical description, because the conventional PB model may become insufficient in those cases. We discuss the conventional PB equation, the corresponding functionals of the electrostatic free energy, including a connection to DFT, simple empirical extensions to this model accounting for finite size of ions, the modified PB theory including ionic correlations and fluctuations, the cell model, and supplementary methods allowing to incorporate site‐bound ions in the PB calculations. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 93–113, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Neutral and Cationic Phosphoramide Adducts of Silicon Tetrachloride: Synthesis and Characterization of Their Solution and Solid‐State Structures
Authors: Denmark Scott E. , Eklov Brian M.
Published: October 2007

The solution and solid‐state structures of hexamethylphosphoramide (HMPA) adducts of tetrachlorosilane (SiCl4) are discussed. In solution, the meridional and facial isomers of the hexa‐coordinate cationic complex 3 HMPA⋅SiCl3+ Cl− (2) predominate at all HMPA concentrations, and are in equilibrium with the hexa‐coordinate neutral trans‐ and cis‐2 HMPA⋅SiCl4 complexes (1), as well as the penta‐coordinate cationic cis‐2 HMPA⋅SiCl3+ Cl− (3). Single crystal X‐ray analyses are reported for the ionized mer‐3 HMPA⋅SiCl3+ HCl2− and the neutral trans‐2 HMPA⋅SiCl4 complexes.
In vivo phosphorylation of regulatory light chain of myosin II in sea urchin eggs and its role in controlling myosin localization and function during cytokinesis
Authors: Uehara Ryota , Hosoya Hiroshi , Mabuchi Issei
Published: October 2007

Phosphorylation of myosin regulatory light chain (RLC) at Ser19 (mono‐phosphorylation) promotes filament assembly and enhances actin‐activated ATPase activity of non‐muscle myosin, while phosphorylation at both Ser19 and Thr18 (di‐phosphorylation) further enhances the ATPase activity. However, it has not well been addressed which type of phosphorylation is important in regulating myosin during cytokinesis. Here, we investigated subcellular localization in sea urchin eggs of mono‐phosphorylated and di‐phosphorylated RLC by both quantitative biochemical and spatiotemporal cytological approaches. Mono‐phosphorylated RLC was dominant in the equatorial cortex throughout the whole process of cytokinesis. Inhibition of myosin light chain kinase (MLCK) decreased mono‐phosphorylated RLC both in the cortex and in the cleavage furrow, and blocked both formation and contraction of the contractile ring. Two different types of ROCK inhibitor gave inconsistent results: H1152 blocked both RLC mono‐phosphorylation in the cleavage furrow and contraction of the contractile ring, while Y27632 affected neither the mono‐phosphorylation nor cell division. These results suggest that there may be other targets of H1152 than ROCK, which is involved in the RLC phosphorylation in the cleavage furrow. Furthermore, it was revealed that localization of myosin heavy chain in the cleavage furrow, but not in the cortex, was perturbed by inhibition of RLC mono‐phosphorylation. These results suggested that RLC mono‐phosphorylation by more than two RLC kinases play a main role in regulation and localization of myosin in the dividing sea urchin eggs. Cell Motil. Cytoskeleton 2007. © 2007 Wiley‐Liss, Inc.
The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer
Authors: Abramowitz Matthew C. , Li Tiaynu , Buyyounouski Mark K. , Ross Eric , Uzzo Robert G. , Pollack Alan , Horwitz Eric M.
Published: October 2007

BACKGROUND.

The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan‐Meier curves and overly favorable estimates when follow‐up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause‐specific mortality (CSM), and overall mortality (OM).

METHODS.

A total of 1831 patients with T1‐4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three‐dimensional conformal methods to at least 60 grays (Gy). The median follow‐up was 71 months and the median RT dose was 72 Gy (range, 60–79 Gy). Cox regression models incorporating BF as a time‐dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate‐specific antigen.

RESULTS.

BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM.

CONCLUSIONS.

The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation. Cancer 2008. © 2007 American Cancer Society.
A fast method for numerical simulation of casting solidification
Authors: Tavakoli Rohallah , Davami Parviz
Published: October 2007

An efficient numerical method for simulation of casting solidification is presented. The presented method is based on a stable explicit finite difference solution of the heat equation in conjunction with the temperature recovery method to incorporate latent heat effect. The computational cost of the presented method is approximately the same as an explicit method (per time step), while it is free from the time step limitation due to the stability criterion. A simple domain decomposition method is included to improve the computational performance of the presented method. The efficiency, stability and accuracy of the presented method are supported with illustrative examples. Copyright © 2007 John Wiley & Sons, Ltd.
Insulin effect on serum potassium and auto‐inhibition of insulin secretion is intact in a patient with leprechaunism despite severe impairment of substrates metabolism
Authors: Luzi Livio , Zoppini Giacomo , Targher Giovanni , Battezzati Alberto , Muggeo Michele , Bonora Enzo
Published: October 2007

Background

The effect of insulin on glucose, protein metabolism, circulating fatty acids (FFA), potassium (K+) and C‐peptide concentrations were investigated in a 12‐year‐old girl with leprechaunism. The mutations do not affect the insulin‐receptor binding affinity and insulin‐stimulated auto‐phosphorylation of the receptor.

Methods

The subject was studied with a primed‐continuous infusion of [6,6 − 2H2] glucose and [1‐13C] leucine during a basal period followed by two steps of insulin infusion (1 and 10 mU/kg/min) of 2 h each, during which plasma glucose level decreased from 131 to 115 and then to 95 mg/dL.

Results

Whole body glucose disposal was virtually unaffected by insulin, slightly decreasing from 21 µmol/kg/min in the basal period to 20 and to 19 µmol/kg/min during the two steps of insulin infusion, respectively. The endogenous leucine flux, an index of proteolysis, was completely insensitive to insulin, being 182, 189 and 180 µmol/kg/min, in the three periods, respectively. The FFA concentration (an indirect index of lipolysis) decreased from 1135 to 799 during step 1. During step 2 the FFA concentration rebounded to 917 µmol/L. The concentration of K+ decreased from 4.2 to 3.2 mmol/L and an infusion of 20 mEq/h of KCl was necessary to prevent further hypokalemia (final value 3.3 mmol/l). The C‐peptide concentration declined from 1.85 to 0.97 and then to 0.29 pmol/mL.

Conclusions

The dissociation of control exerted by insulin on K+ uptake and on β‐cell secretion may rely on a differential expression and folding of the mutated receptors in the different insulin target tissues. Copyright © 2007 John Wiley & Sons, Ltd.
Serum protein patterns in newly diagnosed type 2 diabetes mellitus—influence of diabetic environment and family history of diabetes
Authors: Sundsten Tea , Östenson Claes‐Göran , Bergsten Peter
Published: October 2007

Background

Individuals with normal glucose tolerance (NGT) and type 2 diabetes mellitus (T2DM) represent heterogeneous groups with differences in β‐cell function and genetic background. The aim of the present study was to compare serum protein profiles of NGT and T2DM individuals and determine the influence of the genetic background versus diabetic environment on differentially displayed proteins.

Methods

Surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) was used to compare serum protein profiles of NGT persons and T2DM patients. All participants were from the Stockholm Diabetes Prevention Program (SDPP) cohort. They were selected to have high or low β‐cell function (HOMA‐β) and family history of type 2 diabetes (FHD) or not.

Results

Eight proteins were found to be elevated and five lowered (p < 0.05) in serum of T2DM patients. In a second comparison, the NGT and T2DM groups were divided into persons with FHD and low HOMA‐β and those without FHD and high HOMA‐β. Three proteins were rediscovered and interpreted to be different due to genetic background. Two of these were identified as apolipoprotein C3 (apoC3) and albumin. Ten proteins were interpreted to be not related to FHD, and one of these was identified as transthyretin.

Conclusions

Using the SELDI‐technique, serum protein profiles of NGT and T2DM persons with differences in β‐cell function and FHD were compared. The diabetic environment had a major influence on most of these proteins, while FHD was an important factor for apoC3 and albumin. Copyright © 2007 John Wiley & Sons, Ltd.
Enantioselective Catalytic Formation of Quaternary Stereogenic Centers
Authors: Cozzi Pier Giorgio , Hilgraf Robert , Zimmermann Nicole
Published: October 2007

Enantioselective catalytic formation of tertiary stereogenic centers has nowadays reached an impressive level of maturity, as is reflected in the large variety of available methods that afford high yields and high stereoselectivities. However, the development of stereoselective approaches for the formation of quaternary stereogenic centers still represents an enormous challenge for synthetic chemists. On the other hand, biologically active molecules containing quaternary stereogenic centers provide an incentive for the development of new, selective, and useful processes. Over the last few years, breakthrough work relating to the formation of fully substituted carbon centers has appeared in the literature. In this review we discuss recent highlights of this new direction in catalysis research: the formation of quaternary stereogenic centers by enantioselective catalytic methodologies.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
The liver in celiac disease
Authors: Rubio-Tapia Alberto , Murray Joseph A.
Published: October 2007

Celiac disease is a common (1% prevalence) chronic immune-mediated disorder of the small intestine induced by dietary wheat, barley, and rye. Several hepatic disorders have been described in association with celiac disease. Isolated hypertransaminasemia with nonspecific histologic changes in a liver biopsy is the commonest hepatic presentation of celiac disease. A gluten-free diet normalizes liver enzymes and histologic changes in most patients. Moreover, celiac disease can coexist with autoimmune liver disorders such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Celiac disease has increasingly been reported with a variety of other liver diseases. Thus, the hepatologist needs to consider celiac disease in the differential of abnormal liver blood tests and to be aware of the clinical implications of this frequent disease in patients with liver disorders. The possible mechanisms of liver injury and those common factors that explain the association of celiac disease with liver disorders are discussed. The aims of this article are (1) to review the spectrum and pathogenesis of liver injury related to celiac disease and (2) to provide direction to those caring for patients with chronic liver diseases regarding the detection and effective treatment of celiac disease.