bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic insights into oxidosqualene cyclizations through homology modeling
Authors: Schulz–Gasch Tanja , Stahl Martin 
Published: March 2003

Abstract2,3‐Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)‐2,3‐oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3‐oxidosqualene cyclases are closely related to those of squalene‐hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme‐catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane‐bound nature of OSCs, three‐dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism‐based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure‐based design of antifungal or cholesterol‐lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741–753, 2003
Free energy perturbation and molecular dynamics calculations of copper binding to azurin
Authors: Pappalardo Matteo , Milardi Danilo , Grasso Domenico M. , La Rosa Carmelo 
Published: March 2003

AbstractFree energy perturbation/molecular dynamics simulations have been carried out on copper/azurin systems calculating the binding affinities of copper (II) ion to azurin either in the native or in the unfolded state. In order to test the validity of the strategy adopted for the calculations and to establish what force field is suitable for these kinds of calculations, three different force fields, AMBER, CVFF, and CFF, have been alternatively used for the calculations and the results have been compared with experimental data obtained by spectroscopic titrations of copper (II)/azurin solutions and denaturation experiments. Our findings have pointed out that only CFF gives satisfactory results, thus providing a reliable tool for copper binding simulations in copper protein. © 2003 Wiley Periodicals, Inc. J Comput Chem 6: 779–785, 2003
Balanced network flows. VIII. A revised theory of phase‐ordered algorithms and the O( $\bf\it\sqrt{n}m$ log(n2/m)/log n) bound for the nonbipartite cardinality matching problem
Authors: Fremuth‐Paeger Christian , Jungnickel Dieter 
Published: March 2003

AbstractThis paper closes some gaps in the discussion of nonweighted balanced network flow problems. These gaps all concern the phase‐ordered augmentation algorithm, which can be viewed as the matching counterpart of the Dinic max‐flow algorithm. We show that this algorithm runs in O(n2m) time compared to the bound of O(nm2) derived in Part III of this series and that the bipartiteness requirement can be omitted. The result which deserves attention is the complexity bound for the cardinality matching problem which was shown for the bipartite case by Feder and Motwani. This bound was previously claimed for the general case in a preprint of Goldberg and Karzanov but omitted in later versions of this paper. © 2003 Wiley Periodicals, Inc.
Wheat Starch Gelatinization — the Effects of Sucrose, Emulsifier and the Physical State of the Emulsifier
Authors: Richardson Gisela , Langton Maud , Bark Axel , Hermansson Anne‐Marie 
Published: March 2003

AbstractThe effect of emulsifier and/or sucrose on the swelling of an 8% wheat starch dispersion was evaluated by microscopy. Visual observations of smeared starch pastes under the light microscope, image analysis of the starch granule sizes and viscosity measurements of the starch paste during heating were combined to explain the effects of the added ingredients.Sucrose (12 or 24%, w/w) was shown to delay the swelling of the granules at least up to 50 °C. Above this temperature, the leakage of amylose and granule fragmentation were delayed, but the swelling itself seemed to be accelerated. The polyglycerol ester emulsifier (PGE/MG) at concentrations of 0.5 and 4.0% hindered amylose leakage completely up to 90 °C, followed by a sudden granule rupture. The size of the granules increased up to about 70 °C, but not above this temperature. The monoglyceride (MG) emulsifier in α‐form already had a restrictive effect on the swelling at low temperatures, while the same emulsifier in β‐form did not restrict the swelling until higher temperatures were reached. The emulsifier itself converted into the lamellar state at between 55 and 70 °C, irrespective of the initial form, but the final viscosity was higher in the paste with MG in β‐form. Thus, the initial physical state of the emulsifier was shown to have an influence on the final properties of the gel.
A semi‐smooth Newton method for constrained linear‐quadratic control problems
Authors: Hintermüller M. , Stadler G. 
Published: March 2003

AbstractEs wird ein verallgemeinertes Newton‐Verfahren für die numerische Lösung von linear‐quadratischen Optimalsteuerprozessen mit zweiseitigen Restriktionen an die Steuerung eingeführt und analysiert. Bedingungen werden hergeleitet, unter denen der Algorithmus global konvergiert. Unter Verwendung von Glättungseigenschaften des Lösungsoperators der Zustandsgleichung und einem verallgemeinerten Ableitungsbegriff lassen sich lokal superlineare Konvergenzeigenschaften nachweisen. Umfassende numerische Tests unterstützen die theoretischen Ergebnisse, beweisen die Effizienz des neuen Verfahrens und liefern einen numerischen Nachweis für die Gitterunabhängigkeit des Algorithmus.A semi‐smooth Newton method for the numerical solution of linear‐quadratic optimal control problems with bilateral control constraints is introduced and analyzed. Conditional global convergence results are proved. Based on the smoothing property of the control‐to‐state operator and on generalized derivatives locally superlinear convergence is established. A report on comprehensive numerical tests supports the theoretical results, proves the efficiency of the new algorithm, and allows to argue mesh‐independence.
The Courant‐Herrmann conjecture
Authors: Gladwell G.M.L. , Zhu H. 
Published: March 2003

AbstractThe Courant‐Herrmann Conjecture (CHC) concerns the sign properties of combinations of the Dirichlet eigenfunctions of elliptic pde's, the most important of which is the Helmholtz equation $\Delta u + \lambda \rho u = 0$ for \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$D \in \mathbb{R}^N$\end{document}. If the eigenvalues are ordered increasingly, CHC states that the nodal set of a combination $v = \sum_{i=1}^nc_iu_i$ of the first $n$ eigenfunctions, divides $D$ into no more than $n$ sign domains in which $v$ has one sign. The conjecture is classically known to hold for $N=1$, we conjecture that it is true for rectangular boxes in \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$\mathbb{R}^N (N\geq2)$\end{document}, but show that it is false in general.
Impact of Perioperative Treatment of Recombinant Human Growth Hormone on Cell Immune Function and Intestinal Barrier Function: Randomized, Double‐blind, Controlled Trial
Authors: Liu Wei , Jiang Zhu , Wang Xiu , Shu Hong , Cui Wei , Wilmore Douglas W. 
Published: March 2003

AbstractThe objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo‐controlled randomized double‐blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin‐like growth factor‐1 (IGF‐1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF‐1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation (p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values (p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation‐related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients.
Nitric oxide inhibition of IGF‐1 stimulated proteoglycan synthesis: Role of cGMP
Authors: Studer R. K. , Decker K. , Melhem S. , Georgescu H. 
Published: March 2003

AbstractInsulin‐like growth factor (IGF‐1) is critical for normal development and maintenance of cartilage, however arthritic cartilage responds poorly to IGF‐1; part of this insensitivity is mediated by nitric oxide (NO). These studies test if cGMP is responsible for NO dependent insensitivity to IGF‐1 in chondrocytes in situ in organ culture and in monolayer culture. Lapine cartilage and chondrocytes in monolayer culture and cartilage from osteoarthritic human knees were used. Tissues were exposed to NO from iNOS induced by IL‐1, and proteoglycan synthesis in response to IGF‐1 was evaluated in the presence and absence of cGMP dependent protein kinase (PKG) inhibitors. PKG activators inhibited IGF‐1 responses in cartilage but not chondrocytes in monolayer. IL‐1 stimulated cGMP synthesis in both monolayer and organ cultures. However, PKG inhibitors in cartilage slices but not in monolayer cultures restored response to IGF‐1. PKG activity was detected in both fresh and monolayer chondrocytes, confirming this part of the cGMP signal cascade is intact in both of the preparations evaluated. Arthritic cartilage response to IGF‐1 was restored by both N‐monomethyl‐L‐arginine inhibition of NO synthesis and PKG inhibitors. The data suggests that cGMP mediated effects are critical to NO actions on chondrocytes in situ in the cartilage matrix and supports a role for cGMP in the pathophysiologic effects of NO in osteoarthritis. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Connexin 40 expression in bovine and rat retinas
Authors: Matesic Diane , Tillen Terri , Sitaramayya Ari 
Published: March 2003

AbstractRetinal neurons are extensively coupled through gap junction intercellular channels, but few connexin subtypes have been identified in mammalian retinal neurons. Based on previous findings that retinal gap junctional coupling is modulated by both dopamine and nitric oxide, presumably through connexin phosphorylation, we examined whether the connexin phosphoprotein subtype, connexin 40 (Cx40), was expressed in mammalian retinas. Immunostaining of rat and bovine retinas using Cx40‐specific antibodies from two independent sources showed punctate staining between cells in the outer nuclear layer (ONL) and a sublayer of cells within the inner nuclear layer (INL). In addition, sparse punctate staining was detected in the ganglion cell/axon fiber layers (GCL/AFL). No punctate staining was observed in the outer (OS) or inner segment (IS) layers, and rarely in the outer plexiform layer (OPL) or inner plexiform layer (IPL). Double immunostaining of bovine retinas with antibodies to Go, which stains bipolar cells, and to Cx40, showed little overlap, suggesting these bipolar cells do not express Cx40. Western blot analysis of alkaline‐extracted bovine retinal membranes revealed Cx40 immunopositive bands of about 40 kD (monomer) and 80 kD (dimer). In both locations (monomer and dimer), the bands appeared as doublets, and their immunoreactivity was abolished when the antibody was pre‐adsorbed with immunogenic Cx40 peptide. The doublet at 40 kD co‐migrated with an immunopositive doublet present in heart membranes. Treatment with alkaline phosphatase altered the banding pattern of Cx40. The results suggest that the connexin phosphoprotein subtype, Cx40, is expressed within the neural layers of the mammalian retina.
Chronobiology of the proliferative events related to angiogenesis in mice liver regeneration after partial hepatectomy
Authors: Furnus C.C. , Inda A.M. , Andrini L.B. , García M.N. , García A.L. , Badrán A.F. , Errecalde A.L. 
Published: March 2003

AbstractIn liver regeneration the formation of new capillary blood vessels is a fundamental requirement for cellular proliferation. Vascular endothelial growth factor (VEGF) is involved in the events of angiogenesis, the mRNA of which is expressed in both hepatocytes and non‐parenchymal cells. In this experimental design we try to establish if during liver regeneration in mouse, the expression of VEGF is produced before or after the hepatocytes proliferation. C3H/S adult male mice were divided in three groups in order to study: VEGF expression; S‐phase index (SI); and mitotic activity (MA) of hepatocytes. The results that were analyzed by ANOVA, show that VEGF expression starts to increase 26 h after PH with a peak at 28 h. Furthermore, the DNA synthesis (DNAs) reaches maximal level 42 h after pH, meanwhile the MA of the hepatocytes shows an increase 8 h after the DNAs peak. In conclusion, it could be argued that the chronobiology of the events related to liver regeneration in mice started with a release of VEGF by the hepatocytes, followed by its DNAs and mitosis.
E‐NTPase/E‐NTPDase: a potential regulatory role in E‐kinase/PKA‐mediated CD36 activation
Authors: Kannan Subburaj 
Published: March 2003

AbstractCD36 is a platelet surface receptor protein that plays a major role in platelet aggregation and accumulation that is mediated by parasitic attachment. The CD36 receptor is constitutively phosphorylated by E‐kinase/PKA, resulting in increased affinity for collagen, but preventing spontaneous platelet aggregation. Dephosphorylation of CD36 by protein phosphatase 2A (PP2A) leads to increased affinity for thrombospondin at a different rate than that of collagen‐mediated platelet aggregation. Depletion of the E‐kinase/PKA substrate [ATP]0by E‐NTPase‐mediated hydrolysis, in conjunction with inhibition of PP2A by okadaic acid, could prove to be a valuable tool in inhibiting CD36 activation, thus preventing platelet aggregation and thrombus formation.
Selective blockade of CD28 and not CTLA-4 with a single-chain Fv–α1-antitrypsin fusion antibody
Authors: Vanhove Bernard , Laflamme Geneviève , Coulon Flora , Mougin Marie , Vusio Patricia , Haspot Fabienne , Tiollier Jérôme , Soulillou Jean-Paul 
Published: March 2003

AbstractB7-1 and B7-2 are costimulatory molecules expressed on antigen-presenting cells. The CD28/B7 costimulation pathway is critical for T-cell activation, proliferation, and Th polarization. Blocking both cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and CD28 interactions with a CTLA-4/Ig fusion protein inhibits various immune-mediated processes in vivo, such as allograft rejection and autoimmunity. However, selective blockade of CD28 may represent a better strategy for immunosuppression than B7 blockade, because CTLA-4/B7 interactions have been shown to participate in the extinction of the T-cell receptor–mediated activation signal and to be required for the induction of immunologic tolerance. In addition, selective CD28 inhibition specifically decreases the activation of alloreactive and autoreactive T cells, but not the activation of T cells stimulated by exogenous antigens presented in the context of self major histocompatibility complex (MHC) molecules. CD28 blockade cannot be obtained with anti-CD28 dimeric antibodies, which cluster their target and promote T-cell costimulation, whereas monovalent Fab fragments can block CD28 and reduce alloreactivity. In this study, we report the construction of a monovalent single-chain Fv antibody fragment from a high-affinity antihuman CD28 antibody (CD28.3) that blocked adhesion of T cells to cells expressing the CD28 receptor CD80. Genetic fusion with the long-lived serum protein α1-antitrypsin led to an extended half-life without altering its binding characteristics. The anti-CD28 fusion molecule showed biologic activity as an immuno-suppressant by inhibiting T-cell activation and proliferation in a mixed lymphocyte reaction.
Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome
Authors: Deutsch Samuel , Rideau Alexandra , Bochaton-Piallat Marie-Luce , Merla Giuseppe , Geinoz Antoine , Gabbiani Giulio , Schwede Torsten , Matthes Thomas , Antonarakis Stylianos E. , Beris Photis 
Published: March 2003

AbstractMay-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), Sebastian syndrome (SBS), and Epstein syndrome (EPS) are a group of rare, autosomal dominant disorders characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies, together with variable manifestations of Alport-like symptoms that include high-tone sensorineural deafness, cataracts, and nephritis. These disorders result from mutations in the MYH9 gene, which encodes for the nonmuscle myosin heavy chain A protein (also known as NMMHC-A). To date 20 different mutations have been characterized for this gene, but no clear phenotype-genotype correlation has been established, and very little is known regarding the molecular pathogenesis of this group of diseases. Here, we describe 2 new families with MHA/FTNS phenotypes that have been characterized in terms of their mutations, protein localization in megakaryocytes, protein expression, and mRNA stability. Our findings suggest that, at least for the Asp1424Asn mutation in the MYH9 gene, the phenotypes result from a highly unstable protein. No abnormalities in protein localization or mRNA stability were observed. We hypothesize that haploinsufficiency of the MYH9 results in a failure to properly reorganize the cytoskeleton in megakaryocytes as required for efficient platelet production.
Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis
Authors: Giuliani Nicola , Colla Simona , Lazzaretti Mirca , Sala Roberto , Roti Giovanni , Mancini Cristina , Bonomini Sabrina , Lunghi Paolo , Hojden Magda , Genestreti Giovenzio , Svaldi Mirija , Coser Paolo , Fattori Pier Paolo , Sammarelli Gabriella , Gazzola Gian Carlo , Bataille Regis , Almici Camillo , Caramatti Cecilia , Mangoni Lina , Rizzoli Vittorio 
Published: March 2003

AbstractPatients with multiple myeloma (MM) have increased bone marrow (BM) angiogenesis; however, the proangiogenic properties of myeloma cells and the mechanisms of MM-induced angiogenesis are not completely clarified. The angiopoietin system has been identified as critical in the regulation of vessel formation. In this study we have demonstrated that myeloma cells express several proangiogenic factors, and, in particular, we found that angiopoietin-1 (Ang-1), but not its antagonist Ang-2, was expressed by several human myeloma cell lines (HMCLs) at the mRNA and the protein levels. In a transwell coculture system, we observed that myeloma cells up-regulated the Ang-1 receptor Tie2 in human BM endothelial cells. Moreover, in an experimental model of angiogenesis, the conditioned medium of HMCLs significantly stimulated vessel formation compared with control or vascular endothelial growth factor (VEGF) treatment. The presence of anti-Tie2 blocking antibody completely blunted the proangiogenic effect of XG-6. Finally, our in vitro results were supported by the in vivo finding of Ang-1, but not Ang-2, mRNA and protein expression in purified MM cells obtained from approximately 47% of patients and by high BM angiogenesis in patients with MM positive for Ang-1, suggesting that the angiopoietin system could be involved, at least in part, in MM-induced angiogenesis.
Therapeutic effect of idiotype-specific CD4+ T cells against B-cell lymphoma in the absence of anti-idiotypic antibodies
Authors: Lundin Katrin U. , Hofgaard Peter O. , Omholt Hilde , Munthe Ludvig A. , Corthay Alexandre , Bogen Bjarne 
Published: March 2003

AbstractImmunoglobulin (Ig) variable (V) region idiotypes (Id's) are highly tumor-specific antigens produced by B-lymphoma cells and are promising targets for immunotherapy. Id vaccination has proven effective in experimental mouse models and may possibly prevent recurrence of B lymphomas in humans. It has previously been shown that anti-Id antibodies protect against B-cell lymphoma in the absence of T cells. We here demonstrate in a T-cell–receptor transgenic mouse model that the contrary is also true: Id-specific CD4+ T cells can protect against Id+ B-lymphoma cells in the absence of B cells, antibodies, and CD8+ T cells. Moreover, Id-specific CD4+ T cells have a curative potential since they could be transferred as late as 17 days after subcutaneous tumor cell injection of severe combined immunodeficiency (SCID) mice and still abrogate tumor development in about 50% of mice. Such mice undergo an acute inflammatory swelling with infiltration of neutrophils at the site of tumor injection, which subsides over weeks, with some mice cured and delayed emergence of lymphomas in other mice. Adoptively transferred CD4+ T cells accumulated in the tumor and were activated (CD69+). In vitro experiments demonstrated that memory, but not naive, Id-specific CD4+ T cells kill Id+ B-lymphoma cells. The results show that Id-specific CD4+ T cells, in the absence of antibodies home to subcutaneous Id+ B lymphoma, become activated, induce inflammation, and prevent tumor development.