bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co‐evolution among MHC class I region genes
Authors: Ohta Yuko , Powis Simon J. , Lohr Rebecca L. , Nonaka Masaru , Pasquier Louis Du , Flajnik Martin F. 
Published: October 2003

AbstractIn the frog Xenopus, MHC class I antigen presentation and processing genes (the immunoproteasome LMP2 and LMP7 and the transporter TAP1 and TAP2) seemto be closely linked in a primordial organization. Two distinct lineages of class Ia and LMP7 loci were previously identified, thus strongly suggesting co‐evolution among ‘class I region’ genes. We now show that the Xenopus MHC ‘class I region’ lies between class II and class III genes and we have isolated two distinct alleles at both the TAP1 and TAP2 loci. The alleles at each locus are remarkably divergent from each other and phylogenetic tree analysis revealed in both cases that they diverged from each other 60–100 million years ago (MYA). For lineage‐frequency and linkage analysis, 25 wild‐caught X. laevis and 16 X. tropicalis were examined. The two lineages were present in different frequencies for X. laevis and X. tropicalis. Nevertheless, in all cases, the LMP7, TAP1, and TAP2 lineages were found in a set comprising one of the two lineages. Furthermore, like the LMP7 lineages, the TAP lineages were detected in most Xenopus species that diverged from a common ancestor 80–100 MYA, suggesting that the ‘class I region’ biallelic lineages are under balancing selection.
Structural and kinetic basis for low affinity cross‐reactivity in T cell allorecognition
Authors: Guimezanes Annick , Montero‐Julian Félix , Schmitt‐Verhulst Anne‐Marie 
Published: October 2003

AbstractThe alloreactive BM3.3TCR interacts with high affinity with H‐2Kb loaded with the endogenous peptide pBM1 (INFDFNTI), and shows low affinity cross‐reactivity for H‐2Kb loadedwith a viral peptide VSV8 (RGYVYQGL), CTL activity requiring 103‐fold higher peptide concentration and being highly sensitive to inhibition by anti‐CD8 monoclonal antibody. VSV8 peptides substituted with pBM1/TCR contact residues (N6 and T7) retained low affinity characteristics and among pBM1 peptides substituted with residues Q6 and/or G7 present in VSV8, only pBM1(G7) was recognized, albeit with characteristics akin to those of VSV8. Despite the difference in KD values and the faster dissociation rate of multimeric VSV8/H‐2Kb as compared to pBM1/H‐2Kb complexes, similar TCR occupancy could be achieved with both multimers either at 4 or 37°C. Only TCR engagement with pBM1/H‐2Kb, however, resulted in early (Ca2+ flux) and late(CD69 expression) activation events in naive BM3.3TCR CD8 T cells. CD8 coreceptor, essential for binding of the weak agonists, was dispensable for binding of pBM1/H‐2Kb multimers and their induction of signaling in naive T cells. Hence, high number of TCR and coreceptor engagement by weak agonists fail to substitute for strong agonist TCR engagement that can be coreceptor‐independent and involve a limited number of TCR.
Essential role for TLR4 and MyD88 in the development of chronic intestinal nematode infection
Authors: Helmby Helena , Grencis Richard K. 
Published: October 2003

AbstractExpulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper 2 type response involving IL‐4 and IL‐13. Here we show that Th1 response‐associated susceptibilityis dependent on activation signals mediated by MyD88 and Toll‐like receptor 4 (TLR4). TLR4‐ and MyD88‐deficient mice are highly resistant to chronic T. muris infection and develop strong antigen‐specific Th2 responses in mucosa‐associated lymphoid tissues. Hence, TLR4 and MyD88 are involved not only in the development of pro‐inflammatory responses against bacterial pathogens but are also crucially involved in responses against multicellular organisms such as helminths. These results provide the first demonstration of the critical role of TLR4 and MyD88 in bridging the innate and acquired immune response during gastrointestinal nematode infection.
Endothelial expression of PD‐L1 and PD‐L2 down‐regulates CD8+ T cell activation and cytolysis
Authors: Rodig Nancy , Ryan Timothy , Allen Jessica A. , Pang Hong , Grabie Nir , Chernova Tatyana , Greenfield Edward A. , Liang Spencer C. , Sharpe Arlene H. , Lichtman Andrew H. , Freeman Gordon J. 
Published: October 2003

AbstractInteractions between CD8+ T cells and endothelial cells are important in both protective and pathologic immune responses. Endothelial cells regulate the recruitment of CD8+ Tcells into tissues, and the activation of CD8+ T cells by antigen presentation and costimulatory signals. PD‐L1 and PD‐L2 are recently described B7‐family molecules which bind to PD‐1 on activated lymphocytes and down‐regulate T cell activation. We found that PD‐L1 is expressed on interferon‐γ stimulated cultured human and mouse endothelial cells, while PD‐L2 was found on stimulated human but not mouse endothelial cells. Expression was further up‐regulated by TNF‐α. Antibody blockade of endothelial cell PD‐L1 and PD‐L2 enhanced endothelial cell costimulation of PHA‐activated human CD8+ T cells. Antibody blockade of mouse endothelial cell PD‐L1 enhanced both IFN‐γ secretion and cytolytic activity of CD8+ T cells in response to endothelial cellantigen presentation. These results show that IFN‐γ activated endothelial cells can inhibit T cell activation via expression of the immunoinhibitory PD‐L1 and PD‐L2 molecules. Endothelial expression of PD‐ligands would allow activation and extravasation of T cells without excessive vessel damage. Our findings highlight a potentially important pathway by which endothelial cells down‐regulate CD8+ T cell‐mediated immune responses.
Antibody‐mediated delivery of antigen to chemokine receptors on antigen‐presenting cells results in enhanced CD4+ T cell responses
Authors: Schjetne Karoline W. , Gundersen Hans T. , Iversen Jens‐Gustav , Thompson Keith M. , Bogen Bjarne 
Published: October 2003

AbstractHere, we have investigated if targeting of T cell epitopes to chemokine receptors results in improved CD4+ T cell responses. Mouse monoclonal antibodies (mAb) with κL chains were targeted to various chemokine receptors expressed on human monocytes or immature dendritic cells (DC), and proliferation of cloned human, DR4‐restricted CD4+ T cells specific for mouse Cκ40–48 was measured. When using monocytes as antigen‐presenting cells, mAb specific for CCR1, CCR2, CCR5, and CXCR4 were 100–10,000‐fold more efficient at inducing T cell proliferationwhen compared to isotype‐matched control mAb on a per molecule basis. Targeting of immature DC was less effective and was only seen with anti‐CCR1 and anti‐CXCR4 mAb. Anti‐chemokine receptors mAb required to be processed by the conventional endosomal MHC class II presentation pathway. The mAb did not induce signaling through the chemokine receptors as they failed to induce mobilization of cytosolic Ca2+ and actin polymerization. They also failed to induce APC maturation. The results strongly suggest that chemokine receptors channel antigen into the endocytic pathway for presentation on MHC class II molecules. Targeting T cell epitopes to chemokine receptors by recombinant antibody should be a useful vaccine strategy for the induction of strong CD4+ T cell responses.
Bacterial DNA activates human neutrophils by a CpG‐independent pathway
Authors: Trevani Analía S. , Chorny Alejo , Salamone Gabriela , Vermeulen Mónica , Gamberale Romina , Schettini Jorge , Raiden Silvina , Geffner Jorge 
Published: October 2003

AbstractBacterial DNA stimulates macrophages, monocytes, B lymphocytes, NK cells, and dendritic cells in a CpG‐dependent manner. In this work we demonstrate that bacterial DNA, but not mammalian DNA, induces human neutrophil activation as assessed by L‐selectin shedding, CD11b upregulation, and stimulation of cellular shape change, IL‐8 secretion, and cell migration. Induction of these responsesis not dependent on the presence of unmethylated CpG motifs, as neutrophil stimulatory properties were neither modified by CpG‐methylation of bacterial DNA nor reproduced by oligonucleotides bearing CpG motifs. We found that human neutrophils express Toll‐like receptor (TLR) 9 mRNA. However, as expected for a CpG‐independent mechanism, activation does not involve a TLR9‐dependent signaling pathway; neutrophil stimulation was not prevented by immobilization of bacterial DNA or by wortmannin or chloroquine, two agents that inhibit TLR9 signaling. Of note, both single‐stranded and double‐stranded DNA were able to induce activation, suggesting that neutrophils might be activated by bacterial DNA at inflammatory foci even in the absence of conditions required to induce DNA denaturation. Our findings provide the first evidence that neutrophils might be alerted to the presence of invading bacteria through recognition of its DNA via a novel mechanism not involving CpG motifs.
Control of inflammatory diseases by pathogens: lipids and the immune system
Authors: van der Kleij Desiree , Yazdanbakhsh Maria 
Published: October 2003

AbstractInflammatory diseases such as asthma and diabetes are rising in industrialized countries and the modern lifestyle that is associated with lower exposure to microbes has been held responsible for the increasing prevalence of these diseases. Several studies have shown an inverse association between pathogen‐exposure and allergy or autoimmunity. The mechanisms behind such protective effectshave been investigated at the epidemiological, cellular and molecular level and have provided data on the ability of lipids either derived directly from pathogens or up‐regulated as a result of an infection to down‐regulate immune responses and thereby control inflammatory diseases. In this mini‐review, recent findings and new concepts relating to the immunosuppressive effects of endogenous lipids and those encountered upon exposure to bacteria, protozoa and particularly helminths are discussed. The overview focuses on the modulation of interactions between the antigen‐presenting compartment and T cells to start an anti‐inflammatory "program" with potential to regulate disease processes.
CD30 ligation differentially affects CXCR4‐dependent HIV‐1 replication and soluble CD30 secretion in non‐Hodgkin cell lines and in γ δ T lymphocytes
Authors: Biswas Priscilla , Mantelli Barbara , Delfanti Fanny , Ferrarini Marina , Poli Guido , Lazzarin Adriano 
Published: October 2003

AbstractWe studied whether signaling through CD30, a member of the TNF receptor family, affected acute infection with HIV‐1, encompassing its entire replicative cycle. Several non‐Hodgkin cell lines, targets of CXCR4‐dependent (X4) HIV‐1 infection, were positive for CD30 expression. CD30 ligation induced up‐regulation of viral replication only in certain CD30+ cell lines. Enhancement ofX4 virus replication by CD30 engagement inversely correlated with both CD30 surface density and constitutive NF‐κB activation. Conversely, expression of CD30, but not of other members of the TNF receptor family, was proportional to constitutive NF‐κB binding. Concomitantly, secretion of soluble (s) CD30 increased in all cell lines by CD30 ligation. sCD30 release was enhanced by engagement of CD30 alone and, to a greater extent, by co‐engagement of CD3 also in primary γ δ T lymphocytes, along with complementary modulations of their surface CD30 expression. sCD30‐containing supernatant specifically inhibited HIV‐1 expression induced by CD30 engagement in chronically infected ACH‐2 T cells; thus sCD30 may act as a negative feed‐back molecule. In conclusion, we have delineated novel features of CD30 biology and underline the peculiar link of CD30 expression to constitutive NF‐κB activation which is pivotal to both HIV replication and cell survival.
LIGHT, a new TNF superfamily member, is essential for memory T helper cell‐mediated activation of dendritic cells
Authors: Morel Yannis , Truneh Alemseged , Costello Régis T , Olive Daniel 
Published: October 2003

AbstractLIGHT is a recently identified member of the TNF superfamily that is up‐regulated on activated T cells and can cooperate with CD40L to condition DC for the priming of CTL. In this report, we show that an intracellular pool of LIGHT is found selectively in some CD45RA–CD27+CD4+ "central" memory T cells and to a greater extent in some CD45RA–CD27–CD4+ effector memory T cells. LIGHT, like CD40L, is rapidly up‐regulated on memory CD4+ T cells upon activation. Unlike CD40L, LIGHT up‐regulation on naive T cells is delayed. Stmulation of DC with each subset of memory T cells in the presence of superantigen revealed that CD40L and LIGHT are required for optimal secretion of IL‐12. Moreover, effector memory T cells, which can interact with DC in peripheral tissues, contribute to CCR7 induction on DC. LIGHT and CD40L can also regulate IL‐12 production by CCR7+ DC capable of migration to lymph nodes. These data suggest that both LIGHT and CD40L may be involved in the maintenance or reactivation of secondary Th1 responses.
Probabilistic approach for active control based on structural energy
Authors: Min Kyung‐Won , Hwang Jae‐Seung , Lee Sang‐Hyun , Chung Lan 
Published: October 2003

AbstractThis paper presents an active control algorithm using the probability density function of structural energy. It is assumed that structural energy under excitation has a Rayleigh probability distribution. This assumption is based on the fact that the Rayleigh distribution satisfies the condition that the structural energy is always positive and the occurrence probability of minimum energy is zero. The magnitude of the control force is determined by the probability that the structural energy exceeds the specified target critical energy, and the sign of the control force is determined by the Lyapunov controller design method. The proposed control algorithm shows much reduction of peak responses under seismic excitation compared with the LQR controller, and it can consider the control force limit in the controller design. Also, the chattering problem which sometimes occurs in the Lyapunov controller can be avoided. Copyright © 2003 John Wiley & Sons, Ltd.
A yield displacement distribution‐based approach for strength assignment to lateral force‐resisting elements having strength dependent stiffness
Authors: Tso W. K. , Myslimaj B. 
Published: October 2003

AbstractRecent studies have shown that for many lateral force‐resisting elements (LFRE) stiffness is dependent on strength, and as a result strength assignment to these elements would affect both the strength and stiffness distributions in a structure. Consequently, stiffness distribution cannot be considered known prior to strength assignment. This paper presents a yield displacement distribution‐based strength assignment strategy that does not require the knowledge of stiffness distribution prior to strength assignment. It is shown that structural systems with their center of rigidity (CR) and center of strength (CV) located on the opposite sides of the center of mass (CM) will have small torsional responses under seismic excitation. Copyright © 2003 John Wiley Sons, Ltd.
Experimental study of the semi‐active control of building structures using the shaking table
Authors: Sun Qing , Zhang Ling , Zhou Jinxiong , Shi Qingxuan 
Published: October 2003

AbstractA magnetorheological (MR) damper has been manufactured and tested and a non‐linear model is discussed. The parameters for the model are identified from an identification set of experimental data; these parameters are then used to reconstruct the force vs. displacement and the force vs. velocity hysteresis cycles of the MR damper for the hysteretic model. Then experiments are conducted on a three‐storey frame model using impact excitation, which identifies dynamic parameters of the model equipped with and without the MR damper. Natural frequencies, damping ratios and mode shapes, as well as structural properties, such as the mass, stiffness and damping matrices, are obtained. A semi‐active control method such as a variable structure controller is studied. Based on the ‘reaching law’ method, a feedback controller is presented. In order to evaluate the efficiency of the control system and the effect of earthquake ground motions, both numerical analysis and shaking table tests of the model, with and without the MR damper, have been carried out under three different ground motions: El Centro 1940, Taft 1952, and Ninghe 1976 (Tangshan Earthquake in Chinese). It is found from both the numerical analysis and the shaking table tests that the maximum accelerations and relative displacements for all floors are significantly reduced with the MR damper. A reasonable agreement between the results obtained from the numerical analysis and those from the shaking table tests is also observed. On the other hand, tests conducted at different earthquake excitations and various excitation levels demonstrate the ability of the MR damper to surpass the performance of a comparable passive system in a variety of situations. Copyright © 2003 John Wiley & Sons, Ltd.
Tracking rapidly changing dynamical systems using a non‐parametric statistical method based on wavelets
Authors: Ching Jianye , Glaser Steven D. 
Published: October 2003

AbstractA non‐parametric statistical method of tracking rapidly changing dynamical systems is introduced. The method implements the non‐linear wavelet thresholding estimator to estimate the evolutionary transfer function of the system. The consistency and optimality of the resulting estimate of our method on rapidly changing systems are stated, while no linear estimator can achieve the same optimality. Two examples of real data are studied using this non‐parametric method, including two vertical seismic array case studies and a series of seismic slope experiments. The analysis results are consistent with previous research for the vertical seismic array data. Moreover, our estimate is superior to those from previous research in the sense that our estimate is neither over‐smoothed nor under‐smoothed. The ana‐ lysis results are also consistent with the experimental observations for the seismic slope experimental data. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of reinforcement slippage on the non‐linear response under cyclic loadings of RC frame structures
Authors: Limkatanyu Suchart , Spacone Enrico 
Published: October 2003

AbstractThis paper discusses the importance of including the bond‐slip effects in assessing the response under cyclic loads of reinforced concrete frames. The discussion is based on analyses performed using numerical models which are simple, computationally efficient and capable of representing the salient features of reinforced concrete frames under both static and dynamic loads. The numerical models comprise a displacement‐based, reinforced concrete frame element with bond‐slip and a rigid beam column joint element with bond‐slip. Two applications illustrate the model accuracy and show the importance of including bond‐slip. The first application considers a reinforced concrete beam‐column subassemblage experimentally tested under cyclic loads. The second application considers the shaking table test of a two‐story one‐bay reinforced concrete frame In both cases the analytical results correlate well with the experimental results in terms of strength, displacement demands and hysteretic energy dissipation. Furthermore, the paper shows how the analyses that include bond‐slip yield a better correlation with the experimental results with respect to the analyses that assume a perfect bond. Copyright © 2003 John Wiley & Sons, Ltd.
Ground motion scaling methods for different site conditions and structure characteristics
Authors: Kurama Y. C. , Farrow K. T. 
Published: October 2003

AbstractNon‐linear dynamic time‐history analyses conducted as part of a performance‐based seismic design approach often require that the ground motion records are scaled to a specified level of seismic intensity. Recent research has demonstrated that certain ground motion scaling methods can introduce a large scatter in the estimated seismic demands. The resulting demand estimates may be biased, leading to designs with significant uncertainty and unknown margins of safety, unless a relatively large ensemble of ground motion records is used. This paper investigates the effectiveness of seven ground motion scaling methods in reducing the scatter in estimated peak lateral displacement demands. Non‐linear single‐degree‐of‐freedom systems and non‐linear multi‐degree‐of‐freedom systems are considered with different site conditions (site soil profile and epicentral distance) and structural characteristics (yield strength, period, and hysteretic behavior). It is shown that scaling methods that work well for ground motions representative of stiff soil and far‐field conditions lose their effectiveness for soft soil and near‐field conditions for a wide range of structural characteristics. Copyright © 2003 John Wiley & Sons, Ltd.
Numerical modelling of the pressure wave propagation in the arterial flow
Authors: Pontrelli Giuseppe , Rossoni Enrico 
Published: October 2003

AbstractA differential model of blood flow through an arterial vessel is presented. It consists of a one‐dimensional model describing the non‐linear fluid–wall interaction coupled with a simple lumped parameter model which accounts for outlet boundary conditions. The model includes a local stiffening of the vessel and the wave propagation of disturbances due to prosthetic implantations is also studied. The non‐linear problem is solved by a finite‐difference method on a staggered grid and some numerical simulations are analysed and discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Auto‐regulation and blood flow in the cerebral circulation
Authors: David Tim , Brown Michael , Ferrandez A. 
Published: October 2003

AbstractThe application of computational fluid dynamics (CFD) to model biological flows is quite a recent one. This study presents a CFD model of the Circle of Willis developed to simulate the human cerebrovascular tree. Specifically, we aim to show firstly how the auto‐regulation mechanism can be modelled and secondly how smaller arteries, often not visible by non‐intrusive MR studies, can be detected by making use of the results obtained from the computer simulation. Results show the time‐varying mass flow in each of the efferent vessels and how collateral vessels are even used in naturally ‘balanced’ configurations. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of blood models on flows through a stenosis
Authors: Neofytou Panagiotis , Drikakis Dimitris 
Published: October 2003

AbstractThe paper presents a numerical investigation of non‐Newtonian modelling effects on unsteady periodic flows in a two‐dimensional (2D) channel with a stenosis. The geometry and boundary conditions were chosen so as to reproduce the flow features that are observed in real haemodynamic conditions. Three different non‐Newtonian constitutive equations for modelling the shear characteristics of the blood namely the Casson, power‐law and Quemada models, are utilized. Similarly with previous studies based on Newtonian modelling, the present simulations show the formation of several vortices downstream of the stenosis, as well as substantial variations of the wall shear stress throughout the unsteady cycle. Additionally, it is shown that: (i) there are substantial differences between the results obtained by Newtonian and non‐Newtonian models, and (ii) the prediction of vortex formation, wall shear stress distribution and separation behind the stenosis is strongly dependent on the details of the non‐Newtonian model employed in the simulations. Copyright © 2003 John Wiley & Sons, Ltd.