bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling and Flatness‐Based Control of a Carriage Actuated by Pneumatic Muscles
Authors: Aschemann Harald , Hofer Eberhard P.
Published: November 2004

Pneumatic muscles are innovative tension actuators consisting of textile‐fibre reinforced vulcanised rubber tubing and connection flanges at both ends. They offer several advantages as compared to pneumatic cylinders: significantly less weight, no moving parts within the muscle, and higher maximum force. The main drawback is given by their non‐linear characteristics demanding for sophisticated non‐linear feedback control schemes. This contribution presents a non‐linear control concept for a carriage driven by two pneumatic muscles in parallel connection. First, the modelling of the muscle driven carriage is described in detail. For the resulting non‐linear model the differential flatness property is proven and utilised for a decoupled position and pressure trajectory control. Experimental results from an implementation of this flatness‐based control scheme at a test rig demonstrate the high tracking performance and point out the potential of this new actuator. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Entwurfsmethodik für einen approximativen Normalform‐Beobachter
Authors: Röbenack Klaus
Published: November 2004

Läßt sich ein System in die Beobachter‐Normalform überführen, dann kann man unmittelbar einen Beobachter mit linearer Fehlerdynamik angeben. Die Berechnung der zugehörigen Transformation ist außerordentlich schwierig, da sie die Lösung eines Systems partieller Differentialgleichungen erfordert. Dieses Problem läßt sich mit dem erweiterten Luenberger‐Beobachter umgehen, der auf einer Linearisierung der Fehlerdynamik beruht. In diesem Beitrag wird eine Verallgemeinerung des erweiterten Luenberger‐Beobachters vorgestellt. Bei diesem neuen Zugang werden in der Fehlerdynamik auch Terme zweiter Ordnung kompensiert. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Kinematische Verträglichkeit von Bindungen aufgrund der Benutzerinteraktion
Authors: Li Zhuo , Eberhard Peter , Kübler Lars
Published: November 2004

Die Benutzermanipulationen in einer interaktiven VR‐Umgebung verletzt meistens die kinematischen Zwangsbedingungen einer Mehrkörpersystemsimulation. In diesem Beitrag werden zwei kinematische Ansätze zur Vermeidung oder Reduzierung dieser Verletzung der kinematischen Zwangsbedingungen diskutiert. Beide Ansätze wurden in einer VR‐Umgebung implementiert, getestet und verglichen. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the free‐edge effect in piezoelectric laminated plates
Authors: Artel Jens , Becker Wilfried
Published: November 2004

The present paper considers the effect of electromechanical coupling on the interlaminar stresses and the electric field strengths at free edges of laminated plates with piezoelectric material properties. The results of coupled and uncoupled piezoelectric analyses performed by use of the finite element method are compared. Exemplarily, a symmetric cross‐ply and a symmetric angle‐ply laminate are investigated under uniaxial tension and without any electrical loading. It is shown that the interlaminar stresses at the free edge are significantly higher in the coupled case for the symmetric cross‐ply laminate, whereas the coupling effect for the symmetric angle‐ply laminate is of minor significance. In addition, the occurrence of electric field strengths with singular character is revealed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Anisotropic moisture depending viscoelastic material model for wood
Authors: Schmidt Jörg , Kaliske Michael
Published: November 2004

A moisture depending anisotropic viscoelastic material model is presented in this paper. The necessity of consideration cylindrical anisotropy is caused by the growing process. Wood exhibits different creep characteristics depending on the state of stress. Therefore, the consideration of anisotropic viscoelasticity is required. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Konfigurationswechsel bei plastischen Stoffgesetzen mit dem Übertragungsoperator
Authors: Besdo D. , Ihlemann J. , Kirbach J.
Published: November 2004

Mit Hilfe des Übertragungsoperators in seiner ursprünglichen Form gelingt es in standardisierter Form, Formulierungen tensorieller Relationen in Eulerschen Größen und solcher in Lagrangeschen Größen ineinander zu überführen. Selbst bei enthaltenen tensorwertigen Funktionen tensorieller Argumente gelingt es, die Relation selbst identisch zu erhalten. Während der ursprüngliche Übertragungsoperator [1] auf dem vollständigen Deformationsgradienten $\underline \underline {F} = \underline {g}_i \circ \underline {\tilde g}^i$ basiert, wird das Konzept nun auf Betrachtungen mit einer Zwischenkonfiguration ausgedehnt. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stress mode dependent weighting functions for simulation of asymmetric creep effects
Authors: Mahnken Rolf
Published: November 2004

The paper presents a framework for creep modeling of materials, which experimentelly exhibit different behaviour in different loading scenarios such as tension, compression and shear, respectively. To this end the characterization of the stress modes is obtained in the octahedral plane of the deviatoric stress space in terms of the Lode angle, such that stress mode dependent scalar weighting functions can be constructed. These are exploited to formulate an additive decomposition of the flow rule into a sum of weighted stress mode related quantities. Verification of the approach is succeeded for a superalloy RENE95. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simulation of particle filled polymer networks based on chain statistics under consideration of the Mullins effect
Authors: Böl Markus , Reese Stefanie
Published: November 2004

It is well‐known, that adding amounts of fine particular fillers, such as carbon black, to a polymer matrix can significantly influence the stiffness and the strength of the whole material. Many authors produced important contributions of trying to understand the mechanism of filled rubber. Maybe the most cited models is the Guth‐Gold model [2]. The above described phenomenon is investigated here using the tool of statistical mechanics. We propose in the present contribution a finite element approach which enables us to include for instance non‐affinity, (near‐)incompressibility, inelasticity, non‐Gaussian chain statistics as well as the material behaviour of filled polymers. Therefore special unit cells, consisting of one tetrahedron and six truss elements, have been used. Crucial point of this approach is the fact, that in the truss elements the micromechanical material behaviour of a single chain is implemented. The tetrahedron element provides for (near‐)incompressibility of the material, for more details see Böl & Reese [1]. Putting arbitrary configurations of such unit cells randomly together allows us to simulate complex structures of unfilled materials. To calculate systems consisting of filled materials, in the above described matrix material fine particular fillers in form of finite elements are included to take care for the increasing of the stiffness and the strength of the whole material. Rubber‐like materials and especially filled rubber‐like materials under cyclic loading are characterized through stress‐softening phenomenon, commonly known as the Mullins' effect. This effect is the consequence of chain breakage inside the material. Many models have been developed to simulate this material behaviour, e.g. the ones of Marckmann et al. [3] and Ogden & Roxburgh [5]. In the present proposal this softening effect is analyzed from the physical point of view. Direct comparisons with experimental data suggest that the new approach generates satisfying predictions, particularly for large strain deformations. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Comparison of hyperelastic 2‐D and 3‐D model foams at large deformations
Authors: Demiray S. , Becker W. , Hohe J.
Published: November 2004

The influence of the modeling dimension on the determination of effective properties for hyperelastic foams is investigated by means of regular 2‐D and 3‐D model foams. For calculating the effective stress‐strain relationships of both microstructures, a strain energy based homogenization procedure is employed. The results from numerical analyses show that with a 2‐D model foam the basic deformation mechanisms of the 3‐D model can be captured. Nevertheless, due to the distinct quantitative deviations found from the homogenization analyses, 3‐D modeling approaches should be used if quantitative predictions for the effective material properties are required. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Soft boundary layers in polymeric films
Authors: Diebels Stefan , Steeb Holger , Possart Wulff
Published: November 2004

Application of a polymer on a substrate, e. g. a metal sheet, generates a boundary layer in the polymer. In this boundary layer the properties of the polymer differ from the bulk properties. In the present contribution a mechanical theory based on a structural parameter is presented that allows for the existence of such interphases and, therefore, leads to effective material properties depending on the thickness of the layer. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A thermodynamic consistent model for an assumed transversely isotropic piezoceramic with nonlinear ferroelectric hysteresis
Authors: Romanowski H. , Schröder J.
Published: November 2004

A characteristic feature of ferroelectric crystals is the appearance of a spontaneous polarisation, where its direction can be reversed by an applied electric field. This quantity, that has a maximum value at high electric‐fields, depends on the loading history of the material. In this paper we discuss a thermodynamic consistent phenomenological model for an assumed transversely isotropic ferroelectric crystal, where the history dependency is modelled by internal variables. The anisotropic behaviour is governed by isotropic tensor functions, depending on a finite set of invariants, that satisfy automatically the symmetry relationships of the considered body. The main goal of this investigation is to capture some characteristics of nonlinear ferroelectrica, such as the polarisation‐electric‐field and the strain‐electric‐field (butterfly) hysteresis loops. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the determination of crack initiation directions under mixed mode loading
Authors: Goswami S. , Müller A. , Hohe J. , Becker W.
Published: November 2004

An important issue in the mechanics of multilayered structures is the knowledge of local stress fields. Light‐weight heterogeneous structures with crack‐ or notch‐like discontinuities possess great danger of stress concentration and possible crack initiation leading to failure. In the present study, computational procedure, namely the finite element method, has been used to analyze bimaterial medium with various notch opening angles under arbitrary loading conditions. The prediction of the direction of crack initiation is important for wedge type constructions to gather a first hand knowledge of a potential damage zones which may undermine the integrity of the structure as a whole. The application of computational procedure to predict potential directions of crack initiation gives the flexibility required for different structural configurations, lamina orientations and incorporation of various boundary conditions. Superposition of various external loads to simulate pure mode I, mode II and mixed mode cases can also be carried out with excellent results in computational procedure. All the analysis results are based on the hypothesis of Erdogan and Sih. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Design of a new fracture specimen by 3D singularity analyses
Authors: Kolk K. , Mishuris G. , Kuhn G.
Published: November 2004

A new design of a fracture mechanics specimen is presented. It ensures a valid square‐root singularity along the whole threedimensional crack front under mode‐I conditions. Within the proposed concept it is possible to adjust the angle between the crack front and the free surface in advance. Therefore, the shape of the whole crack front can be influenced in a desired manner. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Material forces in continuum damage material
Authors: Näser Bastian , Kaliske Michael
Published: November 2004

The material force method is present state of the art in computational fracture mechanics. Material forces yield more information than standard approaches like the J‐integral in combination with a highly efficient evaluation in a separate post‐processing step. In this research, the material force method will be applied in tire durability simulations. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Surgical management of pelvic sarcomas in children
Authors: Hosalkar Harish , Dormans John
Published: November 2004

Pelvic sarcomas are uncommon in childhood. Survival rates of children with pelvic sarcomas have shown significant improvements over the past few decades. Correspondingly, there has been an increase in limb‐sparing surgical procedures being performed in these children. This could be attributed in part to the newer generation imaging techniques, wider armamentarium of surgical techniques of reconstruction, and limb‐salvage and advances in neo‐adjuvant chemotherapy and radiotherapy. Reconstruction after resection of pelvic sarcomas while preserving function of the hip and limb can be extremely challenging especially in children where there are issues of growth potential and limb‐length discrepancies. This article focuses on the presentation and epidemiology of different types of pelvic sarcomas in children, the current state‐of‐art of imaging and surgical management of children with pelvic sarcomas. © 2004 Wiley‐Liss, Inc.
Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group
Authors: Ek Torben , Mellander Lotta , Andersson Bengt , Abrahamsson Jonas
Published: November 2004

Objective

The aim was to examine the immune reconstitution after current chemotherapy for childhood ALL, with a special focus on finding immunologic variables that predict a poor immune response to vaccinations.

Procedure

In a cross‐sectional study of 31 children after treatment with the NOPHO ALL‐1992 protocol peripheral blood lymphocyte subsets, T‐ and B‐cell function in vitro and serum immunoglobulins (Ig) were measured. All patients were examined once, at 1 or at 6 months after cessation of chemotherapy, immediately before vaccination with DT and Hib.

Results

Lymphocytes, T‐cells, and CD4+ T‐cells were low at 6 months after treatment. Naïve T‐cell subsets were more reduced than memory subsets. In the high risk (HR) ALL group, CD8+ T‐cells were reduced at 6 months. NK‐cells were low at 1 month, but normal at 6 months; however, the CD3+CD56+ (NKT) subset was reduced at both time points. Total B‐cell number was low at 1 month, but normal at 6 months. A relative increase of CD5+ B‐cells (B‐1 cells) was evident, particularly in the HR group. Antigen‐independent T‐ and B‐cell function in vitro were affected at 1 month, but virtually normalized at 6 months. Serum IgM level was decreased at 1 month and IgG3 level was increased at 1 and 6 months.

Conclusions

This study shows that immune reconstitution after childhood ALL is slower than previously reported and emphasizes the influence of treatment intensity. The most intensively treated patients still have persistent abnormalities in T‐, B‐, and NK‐cell subsets at 6 months post therapy and show a poor response to immunization with T‐cell dependent antigens. In the HR group, routine re‐immunizations before this time point are of limited benefit, and the effect of repeated vaccinations should be evaluated. © 2004 Wiley‐Liss, Inc.
Computational linear dependence in molecular electronic structure calculations using universal basis sets
Authors: Moncrieff D. , Wilson S.
Published: November 2004

Distributed universal even‐tempered basis sets have been developed over recent years that are capable of supporting Hartree–Fock energies to an accuracy approaching the sub‐μHartree level. These basis sets have also been exploited in correlation studies, in applications to polyatomic molecules, and in the calculation of electric properties, such as multipole moments, polarizabilities, and hyperpolarizabilities. Jorge and coworkers have also developed universal basis sets and have recently reported applications to diatomic molecular systems. In this article, we compare the molecular calculations reported by Jorge and coworkers with our previous studies. Particular attention is given to the degree of computational linear dependence associated with the various basis sets employed and the consequential effects of the accuracy of the calculated energies. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Smithsoniarhynches, a new genus of interstitial Gnathorhynchidae (Platyhelminthes: Kalyptorhynchia) from Mosquito Lagoon and Indian River Lagoon, Florida
Authors: Hochberg Rick
Published: November 2004

A new genus of marine, interstitial schizorhynch (Platyhelminthes: Kalyptorhynchia) is described from sediment collected in Mosquito Lagoon and Indian River Lagoon, Florida, USA. Smithsoniarhynches is characterized by the presence of proboscis hooks constructed of ten individual spine-like teeth that emerge separately from a basal plate. Histology and confocal laser scanning microscopy are used to reveal additional details of the proboscis musculature and reproductive anatomy. The type species, Smithsoniarhynches sherryreedae sp. nov., is characterized by well-developed proboscis pads, four pairs of proboscis retractor muscles, and a pharynx in the midbody region. The male reproductive system consists of an anterior testis, muscular seminal vesicle, copulatory bulb lined with spiral and circular muscles, and a sclerotic stylet. The female system consists of an unpaired vitellarium, ovary, uterus and bursa. The bursa tissue surrounds a muscular bursa seminalis with distinct sphincter muscles. The new genus is compared with the known 11 genera within the Gnathorhynchidae to establish a tentative hypothesis of relationships.
Feeding habits of the burrowing shrimp Alpheus macellarius
Authors: Palomar N.E. , Juinio-Meñez M.A. , Karplus I.
Published: November 2004

The diet and feeding behaviour of the burrowing shrimp Alpheusmacellarius (Decapoda: Alpheidae) in sea grass beds in the Philippines were evaluated in the present study through field and laboratory activities. Sediment organic matter and sea grass appear to be important food sources for the shrimp based on the combined results of field surveys, gut content, stable isotope (δ13C) and sediment C content analyses. There was a significant positive correlation between organic matter content in the sediment and shrimp densities. In terms of behaviour, observations under controlled set-ups detected marked trends in duration and frequency of feeding. Feeding bouts became longer and more recurrent as the days progressed. Periodicity was exhibited with burrowing generally performed in the morning and feeding in the afternoon. A deposit-feeding mode was predominant in tank conditions as demonstrated by the shrimp's behaviour and burrow features.
Records of the leatherback sea turtle (Dermochelys coriacea) on the Brazilian coast, 1969–2001
Authors: Barata Paulo C.R. , Lima Eduardo H.S.M. , Borges-Martins Márcio , Scalfoni Juarez T. , Bellini Claudio , Siciliano Salvatore
Published: November 2004

Data from several sources and original data are presented regarding sightings, strandings and incidental captures of leatherback sea turtles (Dermochelys coriacea) on the Brazilian coast in a 33 year period, from 1969 to 2001. Two of the turtles were small juveniles (curved carapace length=40 cm and approximately 85 cm) and the remaining animals with known carapace size were large juveniles or adults. The origin of leatherbacks observed in Brazil is unknown. Several colonies in South America, including a Brazilian one, in the Caribbean, in western Africa and even in eastern South Africa could be the source of these turtles. The data presented here suggest that more effort should be directed to the assessment of the impact of fishing gear and marine pollution on leatherbacks and that systematic surveys on beaches should be maintained in order to monitor long term fluctuations in stranding levels and spatial stranding patterns. Genetic studies and satellite telemetry would be helpful in clarifying the origin of leatherbacks stranded or incidentally captured on the Brazilian coast.
Diet of minke whales Balaenoptera acutorostrata in Scottish (UK) waters with notes on strandings of this species in Scotland 1992–2002
Authors: Pierce G.J. , Santos M.B. , Reid R.J. , Patterson I.A.P. , Ross H.M.
Published: November 2004

During 1992–2002 approximately 110 strandings of minke whales Balaenoptera acutorostrata were recorded in Scotland (UK). Most strandings were recorded between April and November, with a peak of strandings of males in July and August. There were two length modes at 4–6 m and 7–10 m. Stomach contents samples were obtained from ten animals. The diet comprised mainly sandeels (Ammodytidae, around two-thirds of the diet by number or weight) and clupeids (herring Clupea harengus and sprat Sprattus sprattus). Results on diet are consistent with results from whaling catches in the North Sea. The possibility that minke whales compete with fisheries is discussed.
Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries
Authors: Prieto Dolores , Rivera de los Arcos Luis , Martínez Pilar , Benedito Sara , García‐Sacristán Albino , Hernández Medardo
Published: November 2004

The distribution of neuropeptide Y (NPY)‐immunorective nerves and the receptors involved in the effects of NPY upon electrical field stimulation (EFS)‐ and noradrenaline (NA)‐elicited contractions were investigated in horse penile small arteries.

NPY‐immunoreactive nerves were widely distributed in the erectile tissues with a particularly high density around penile intracavernous small arteries.

In small arteries isolated from the proximal part of the corpora cavernosa, NPY (30 nM) produced a variable modest enhancement of the contractions elicited by both EFS and NA. At the same concentration, the NPY Y1 receptor agonist, [Leu31, Pro34]NPY, markedly potentiated responses to EFS and NA, whereas the NPY Y2 receptor agonist, NPY(13–36), enhanced exogenous NA‐induced contractions.

In arteries precontracted with NA, NPY, peptide YY (PYY), [Leu31, Pro34]NPY and the NPY Y2 receptor agonists, N‐acetyl[Leu28,31]NPY (24–36) and NPY(13–36), elicited concentration‐dependent contractile responses. Human pancreatic polypeptide (hPP) evoked a biphasic response consisting of a relaxation followed by contraction. NPY(3–36), the compound 1229U91 (Ile‐Glu‐Pro‐Dapa‐Tyr‐Arg‐Leu‐Arg‐Tyr‐NH2, cyclic(2,4′)diamide) and eventually NPY(13–36) relaxed penile small arteries.

The selective NPY Y1 receptor antagonist BIBP3226 ((R)‐N2‐(diphenacetyl)‐N‐[(4‐hydroxyphenyl)methyl]D‐arginineamide) (0.3 μM) shifted to the right the concentration–response curves to both NPY and [Leu31, Pro34]NPY and inhibited the contractions induced by the highest concentrations of hPP but not the relaxations observed at lower doses.

In the presence of the selective NPY Y2 receptor antagonist BIIE0246 ((S)‐N2‐[[1‐[2‐[4‐[(R,S)‐5,11‐dihydro‐6(6h)‐oxodibenz[b,e]azepin‐11‐y1]‐1‐piperazinyl]‐2‐oxoethyl]cyclo‐pentyl‐N‐[2‐[1,2‐dihydro–3,5 (4H)‐dioxo‐1,2‐diphenyl‐3H‐1,2, 4‐triazol‐4‐yl]ethyl]‐argininamide) (0.3 μM), the Y2 receptor agonists NPY(13–36) and N‐acetyl[Leu28,31]NPY (24–36) evoked potent slow relaxations in NA‐precontracted arteries, under conditions of nitric oxide (NO) synthase blockade.

Mechanical removal of the endothelium markedly enhanced contractions of NPY on NA‐precontracted arteries, whereas blockade of the neuronal voltage‐dependent Ca2+ channels did not alter NPY responses.

These results demonstrate that NPY can elicit dual contractile/relaxing responses in penile small arteries through a heterogeneous population of postjunctional NPY receptors. Potentiation of the contractions evoked by NA involve both NPY Y1 and NPY Y2 receptors. An NO‐independent relaxation probably mediated by an atypical endothelial NPY receptor is also shown and unmasked in the presence of selective antagonists of the NPY contractile receptors.

British Journal of Pharmacology (2004) 143, 976–986. doi:10.1038/sj.bjp.0706005
Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA treatment
Authors: Ben Yong , Smith Andrew P , Schiller Peter W , Lee Nancy M
Published: November 2004

Previously, we reported that H‐2′,6′‐dimethyltyrosine [Dmt1]‐D‐Arg‐Phe‐Lys‐NH2 (DALDA), an analogue of the naturally occurring opioid peptide dermorphin, is a highly potent and selective mu receptor agonist with low cross‐tolerance to morphine. In the present study, we investigated the effect of treating mice chronically with [Dmt1]DALDA. The AD50 of [Dmt1]DALDA (s.c.) increased eight‐fold in animals given this drug chronically; in contrast, the AD50 increased two‐fold in mice chronically treated with morphine. The AD50 of morphine (s.c.) in these [Dmt1]DALDA‐treated animals was increased more than 120 times, while that of the more selective μ agonist [D‐Ala2‐MePhe4‐Gly‐ol5]enkephalin (DAMGO) given intrathecally was increased more than 240 times. However, the AD50 of DAMGO given intracerebroventricularly was essentially the same in animals treated chronically with [Dmt1]DALDA as in naïve animals. The dose of naloxone required to precipitate withdrawal in [Dmt1]DALDA‐treated animals was 20 times lower than that in morphine‐tolerant animals.

Using real‐time quantitative PCR, we found that expression of the μ opioid receptor, δ opioid receptor, preproenkephalin and preprodynorphin genes was upregulated in the brain by [Dmt1]DALDA treatment. No significant changes in expression of opioid receptor or opioid peptide genes were detected in the spinal cord of [Dmt1]DALDA‐treated mice, nor in the brain or spinal cord of morphine‐treated mice. We conclude that a high degree of tolerance to [Dmt1]DALDA develops in the spinal cord but not brain, and cannot be accounted for by changes in expression of opioid receptors or opioid peptides in these tissues.

British Journal of Pharmacology (2004) 143, 987–993. doi:10.1038/sj.bjp.0706007
Structural Basis for the Restoration of TCR Recognition of an MHC Allelic Variant by Peptide Secondary Anchor Substitution
Authors: Miley Michael J. , Messaoudi Ilhem , Metzner Beatrix M. , Wu Yudong , Nikolich-Žugich Janko , Fremont Daved H.
Published: November 2004

Major histocompatibility complex (MHC) class I variants H-2Kb and H-2Kbm8 differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B498-505 epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against Kb–HSV8 cannot recognize H-2Kbm8–HSV8. However, substitution of SerP2 to GluP2 (peptide H2E) reversed T cell receptor (TCR) recognition; H-2Kbm8–H2E was recognized whereas H-2Kb–H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface.
Hepatic Endothelial CCL25 Mediates the Recruitment of CCR9+ Gut-homing Lymphocytes to the Liver in Primary Sclerosing Cholangitis
Authors: Eksteen Bertus , Grant Allister J. , Miles Alice , Curbishley Stuart M. , Lalor Patricia F. , Hübscher Stefan G. , Briskin Michael , Salmon Mike , Adams David H.
Published: November 2004

Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433–1435). However, the liver and bowel inflammation are rarely concomitant, and PSC can develop in patients whose colons have been removed previously. We hypothesized that PSC is mediated by long-lived memory T cells originally activated in the gut, but able to mediate extra-intestinal inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S. Jalkanen, and D.H. Adams. 2002. Lancet. 359:150–157). In support of this, we show that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to the liver by aberrant expression of the gut-specific chemokine CCL25 that activates α4β7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium. This is the first demonstration in humans that T cells activated in the gut can be recruited to an extra-intestinal site of disease and provides a paradigm to explain the pathogenesis of extra-intestinal complications of IBD.
FINE STRUCTURAL STUDIES ON THE INTERPHASE AND DIVIDING APICAL CELLS OF SPHACELARIA TRIBULOIDES (PHAEOPHYTA)1
Authors: Katsaros Christos , Galatis Basil , Mitrakos Konstantinos
Published: November 2004

The apical cells of Sphacelaria tribuloides Menegh. are larger than other thallus cells, contain more organelles and appear polarized. Their tip portion, where they grow, contains a well developed Golgi apparatus, abundant endoplasmic reticulum (ER) membranes, mitochondria, chloroplasts and a large number of small vacuoles. It seems likely that a continuous flow of membranous material from the ER membranes to the dictyosomes and from the latter to the plasmalemma of the extending tip portion takes place. In contrast, the basal pole possesses fewer organelles and is occupied mainly by large‐sized, sometimes central vacuoles. The apical cells undergo two distinct types of highly asymmetrical differential divisions giving rise to cells of the thallus and hair initials. During the early stages of mitosis the nuclear envelope remains intact, except for fenestrated poles. Microtubules pass through the fenestrae into the nucleoplasm. During meta‐phase, a typical chromosome plate is organized. The sites of attachment of spindle microtubules to the chromosomes are structurally different from the rest of the chromosomes. At late anaphase, the nuclear envelope breaks down completely. During telophase, a new membrane encloses the chromosomes which are decondensed and the nucleoli are reorganized. Cytokinesis proceeds long after mitosis at a stage in which the nuclei have increased in size and have moved farther apart. A membranous furrow develops centripetally, without the participation of microtubules. However, microtubules traverse the thin cytoplasmic strands which, in both interphase and cytokinetic cells, meander among the vacuoles of the basal pole of the cell and the internuclear space. Dictyosomes appear to be involved in the subsequent wall deposition.
The steppe pika Ochotona pusilla in Britain, and a new northerly record
Authors: FISHER C. T. , YALDEN D. W.
Published: November 2004

The known localities for steppe pika Ochotona pusilla, which occurred in Britain during Late Pleistocene times, are reviewed. A previously misidentified lower jaw, from Helsfell Cave in the Lake District, Cumbria extends the known range of this species in Britain 100 km further north.
Still Causing Trouble: The Conservative Parliamentary Party
Authors: COWLEY PHILIP , STUART MARK
Published: November 2004

There have been relatively few backbench rebellions on the Conservative benches in the Commons since 2001, but division manifested itself on three significant occasions: over the Children and Adoption Bill (when the leadership insisted on applying a whip to a vote that many thought should have been 'free'), over Lords reform (where on a free vote a majority of Conservative MPs voted against their leadership's preferred position) and over Iraq (where the divisions were smaller than on the Labour side of the House but where there was a qualitative dimension to the rebellion). Most importantly of all, the events of October 2003, when Iain Duncan Smith was removed as party leader, showed how much power remained with Conservative MPs: they initiated the vote of confidence, in which they alone participated, and the emergence of Michael Howard as the 'unity' candidate meant that the grassroots were denied any role in the change of leadership.
The Extra‐Parliamentary Tory Party: McKenzie Revisited
Authors: KELLY RICHARD
Published: November 2004

This chapter almost coincides with the fiftieth anniversary of Robert McKenzie's British Political Parties, a study which contested that power in the Tory party was centralised in its Parliamentary leadership, with its constituency members having only a marginal influence. The chapter revisits McKenzie's analysis in the light of developments since 2001, particularly the victory of Iain Duncan Smith in that year's 'democratised' Conservative leadership contest.

The chapter argues that Duncan Smith's victory strengthened McKenzie's claim that democratised parties are seldom popular, and describes how IDS, ironically, spawned reforms that diminished his extra‐Parliamentary supporters. But the chapter is also an updated reminder that McKenzie underrated grass root power in certain areas ‐ notably candidate selection ‐ and suggests a lesson from the Tories' short‐lived revival under Michael Howard, namely that long‐term party recovery requires an energised party membership as well as a competent party leader.
Corporate Investment and Asset Price Dynamics: Implications for the Cross‐section of Returns
Authors: CARLSON MURRAY , FISHER ADLAI , GIAMMARINO RON
Published: November 2004

We show that corporate investment decisions can explain the conditional dynamics in expected asset returns. Our approach is similar in spirit to Berk, Green, and Naik (1999), but we introduce to the investment problem operating leverage, reversible real options, fixed adjustment costs, and finite growth opportunities. Asset betas vary over time with historical investment decisions and the current product market demand. Book‐to‐market effects emerge and relate to operating leverage, while size captures the residual importance of growth options relative to assets in place. We estimate and test the model using simulation methods and reproduce portfolio excess returns comparable to the data.
Near‐sighted Justice
Authors: BERNHARDT DAN , NOSAL ED
Published: November 2004

Chapter 11 structures complex negotiations between creditors and debtors that are overseen by a bankruptcy court. We identify conditions where the court should sometimes err in determining which firms should be liquidated. Such errors affect actions by both good and bad entrepreneurs. We first characterize the optimal error rate without renegotiation. When creditors and debtors can renegotiate to circumvent an error‐riven court, for one class of actions a blind court that ignores all information is optimal. For another class, the court should place the burden of proof on the entrepreneur. The robust feature is that the court should sometimes err.
Systemic Risk and International Portfolio Choice
Authors: DAS SANJIV RANJAN , UPPAL RAMAN
Published: November 2004

Returns on international equities are characterized by jumps; moreover, these jumps tend to occur at the same time across countries leading to systemic risk. We capture these stylized facts using a multivariate system of jump‐diffusion processes where the arrival of jumps is simultaneous across assets. We then determine an investor's optimal portfolio for this model of returns. Systemic risk has two effects: One, it reduces the gains from diversification and two, it penalizes investors for holding levered positions. We find that the loss resulting from diminished diversification is small, while that from holding very highly levered positions is large.
Yersinia enterocolitica
Adhesin A Induces Production of Interleukin-8 in Epithelial Cells
Authors: Schmid Yvonne , Grassl Guntram A. , Bühler Oliver T. , Skurnik Mikael , Autenrieth Ingo B. , Bohn Erwin
Published: November 2004

The major invasive factor of
Yersinia enterocolitica
, the invasin (Inv) protein, induces proinflammatory host cell responses, including interleukin-8 (IL-8) secretion from human epithelial cells, by engagement of β1 integrins. The Inv-triggered β1 integrin signaling involves the small GTPase Rac; the activation of MAP kinases, such as p38, MEK1, and JNK; and the activation of the transcription factor NF-κB. In the present study, we demonstrate that
Y. enterocolitica
YadA, which is a major adhesin of
Y. enterocolitica
with pleiotropic virulence effects, induces IL-8 secretion in epithelial cells. The abilites of YadA and Inv to promote adhesion to and invasion of HeLa cells and to induce IL-8 production by the cells were investigated by expression of YadA and Inv in
Escherichia coli
. While YadA mediates efficacious adhesion to HeLa cells, it mediates marginal invasion compared with Inv. Both YadA and Inv trigger comparable levels of IL-8 production. Conformational changes of the YadA head domain by mutation of NSVAIG-S motifs, which abolish collagen binding, also abolish adhesion of
Yersinia
to HeLa cells and YadA-mediated IL-8 secretion. Furthermore, experiments in which blocking antibodies against β1 integrins were used demonstrate that β1 integrins are crucial for YadA-mediated IL-8 secretion. Inhibitor studies demonstrate the involvement of small GTPases and MAP kinases, such as p38, MEK1, and JNK, indicating that β1 integrin-dependent signaling mediated by Inv or YadA involves similar signaling pathways. These data present YadA, in addition to Inv, YopB, and
Yersinia
lipopolysaccharide, as a further inducer of proinflammatory molecules by which
Y. enterocolitica
might promote inflammatory tissue reactions.
The Major Histocompatibility Complex Haplotype Affects T-Cell Recognition of Mycobacterial Antigens but Not Resistance to
Mycobacterium tuberculosis
in C3H Mice
Authors: Kamath Arati B. , Alt Jennifer , Debbabi Hajer , Taylor Chad , Behar Samuel M.
Published: November 2004

Both innate and adaptive immunity play an important role in host resistance to
Mycobacterium tuberculosis
infection. Although several studies have suggested that the major histocompatibility complex (MHC) haplotype affects susceptibility to infection, it remains unclear whether the modulation of T-cell immunity by the MHC locus determines the host's susceptibility to tuberculosis. To determine whether allelic differences in the MHC locus affect the T-cell immune response after
M. tuberculosis
infection, we infected inbred and H-2 congenic mouse strains by the respiratory route. The H-2 locus has a profound effect on the antigen-specific CD4
+
-T-cell response after
M. tuberculosis
infection. CD4
+
T cells from infected mice of the H-2
b
haplotype produced more gamma interferon (IFN-γ) after in vitro stimulation with mycobacterial antigens than mice of the H-2
k
haplotype. A higher level of IFN-γ was also detected in bronchoalveolar lavage fluid from infected mice of the H-2
b
haplotype. Furthermore, C3.SW-H2
b
/SnJ mice generate and recruit activated T cells to the lung after infection. Despite a robust immune response, C3.SW-H2
b
/SnJ mice succumbed to infection early and were similarly susceptible to infection as other C3H (H-2
k
) substrains. These results suggest that although the MHC haplotype has a profound impact on the T-cell recognition of
M. tuberculosis
antigens, the susceptibility of C3H mice to infection is MHC independent.
Protective Immunity against
Eimeria acervulina
following In Ovo Immunization with a Recombinant Subunit Vaccine and Cytokine Genes
Authors: Ding Xicheng , Lillehoj Hyun S. , Quiroz Marco A. , Bevensee Erich , Lillehoj Erik P.
Published: November 2004

A purified recombinant protein from
Eimeria acervulina
(3-1E) was used to vaccinate chickens in ovo against coccidiosis both alone and in combination with expression plasmids encoding the interleukin 1 (IL-1), IL-2, IL-6, IL-8, IL-15, IL-16, IL-17, IL-18, or gamma interferon (IFN-γ) gene. When used alone, vaccination with 100 or 500 μg of 3-1E resulted in significantly decreased oocyst shedding compared with that in nonvaccinated chickens. Simultaneous vaccination of the 3-1E protein with the IL-1, -15, -16, or -17 gene induced higher serum antibody responses than 3-1E alone. To evaluate protective intestinal immunity, vaccinated birds were challenged with live
E. acervulina
oocysts 14 days posthatch, and fecal-oocyst shedding and body weight gain were determined as parameters of coccidiosis. Chickens vaccinated with 3-1E protein showed significantly lower oocyst shedding and normal body weight gain than nonvaccinated and infected controls. Simultaneous immunization with 3-1E and the IL-2, -15, -17, or -18 or IFN-γ gene further reduced oocyst shedding compared with that achieved with 3-1E alone. These results provide the first evidence that in ovo vaccination with the recombinant 3-1E
Eimeria
protein induces protective intestinal immunity against coccidiosis, and this effect was enhanced by coadministration of genes encoding immunity-related cytokines.
Immunostimulating Properties of Intragastrically AdministeredAcetobacter-Derived Soluble Branched (1,4)-β-d-Glucans Decrease Murine Susceptibility toListeria monocytogenes
Authors: Li Wei , Yajima Toshiki , Saito Kimika , Nishimura Hitoshi , Fushimi Takashi , Ohshima Yoshifumi , Tsukamoto Yoshinori , Yoshikai Yasunobu
Published: November 2004

We previously found that AC-1, an extracellular polysaccharide, produced byAcetobacter xylinumand composed of (1,4)-β-d-glucan with branches of glucosyl residues, showed a strong activity to induce production of interleukin-12 (IL-12) p40 and tumor necrosis factor alpha by macrophages in vitro via Toll-like receptor 4 (TLR-4) signaling. In the present study, we examined the effect of oral administration of AC-1 on protective immunity againstListeria monocytogenes. Mice were given AC-1 or phosphate-buffered saline (PBS) intragastrically 2 days before, on the day of, and 2 days after an intraperitoneal inoculation ofL. monocytogenes. The survival rate of AC-1-treated mice was significantly improved and bacterial growth in AC-1-treated mice was severely retarded compared to those of PBS-treated mice after infection withL. monocytogenes. IL-12 p40 levels in serum and magnitudes of CD4+Th1 and CD8+Tc1 responses againstListeriaantigen were significantly higher in AC-1-treated mice than in PBS-treated mice. The effect of AC-1 on antilisterial activity was diminished in C3H/HeJ mice carrying mutated TLR-4. Thus, AC-1, a potent IL-12 inducer through TLR-4, enhanced protective immunity againstL. monocytogenesvia augmentation of Th1 responses. These results suggest that infectious processes driven by intracellular microorganisms could be prevented to develop by the (1,4)-β-d-glucan.
Oral Vaccination of BALB/c Mice withSalmonella entericaSerovar Typhimurium ExpressingPseudomonas aeruginosaO Antigen Promotes Increased Survival in an Acute Fatal Pneumonia Model
Authors: DiGiandomenico Antonio , Rao Jayasimha , Goldberg Joanna B.
Published: November 2004

Pseudomonas aeruginosais a leading cause of nosocomial pneumonia. We compared the efficacies of oral and intraperitoneal (i.p.) vaccinations of BALB/c mice with attenuatedSalmonella entericaserovar Typhimurium SL3261 expressingP. aeruginosaserogroup O11 O antigen to protect againstP. aeruginosainfection in an acute fatal pneumonia model. Oral and i.p. vaccines elicited O11-specific serum immunoglobulin G (IgG) antibodies, but IgA was observed only after oral immunization. Challenge of orally vaccinated mice with an O11 strain (9882-80) at 6 and 12 times the 50% lethal dose showed increased survival in mice that received the vaccine compared to phosphate-buffered saline (PBS)- and vector-treated controls; no difference in survival was seen with a heterologous strain, 6294 (serogroup O6). In addition, significant protection against 9882-80 was not observed in i.p. vaccinated animals. Bronchoalveolar lavage fluid taken from immunized mice harbored O11-specific IgA and IgG in orally immunized mice but only modest levels of IgG in i.p. vaccinated mice. To correlate protection, opsonophagocytosis assays were performed with pooled sera from orally immunized animals. Efficient killing of five O11 clinical isolates was observed, while no killing was noted with 6294, indicating that the recombinant SL3261 oral vaccine induces an O11-specific reaction. We next determined the ability of orally vaccinated animals to clear bacteria from their lungs. FollowingP. aeruginosachallenge, the numbers of viable bacteria were significantly fewer in orally vaccinated animals than in PBS- and vector-treated controls. Our results suggest that oral immunization with recombinant SL3261 is efficacious in protection against pneumonia caused byP. aeruginosa.
First-Time Isolation and Characterization of a Bacteriophage Encoding the Shiga Toxin 2c Variant, Which Is Globally Spread in Strains of
Escherichia coli
O157
Authors: Strauch Eckhard , Schaudinn Christoph , Beutin Lothar
Published: November 2004

A bacteriophage encoding the Shiga toxin 2c variant (Stx2c) was isolated from the human
Escherichia coli
O157 strain CB2851 and shown to form lysogens on the
E. coli
K-12 laboratory strains C600 and MG1655. Production of Stx2c was found in the wild-type
E. coli
O157 strain and the K-12 lysogens and was inducible by growing bacteria in the presence of ciprofloxacin. Phage 2851 is the first reported viable bacteriophage which carries an
stx
2c
gene. Electron micrographs of phage 2851 showed particles with elongated hexagonal heads and long flexible tails resembling phage lambda. Sequence analysis of an 8.4-kb region flanking the
stx
2c
gene and other genetic elements revealed a mosaic gene structure, as found in other Stx phages. Phage 2851 showed lysis of
E
.
coli
K-12 strains lysogenic for Stx phages encoding Stx1 (H19), Stx2 (933W), Stx (7888), and Stx1c (6220) but showed superinfection immunity with phage lambda, presumably originating from the similarity of the
c
I repressor proteins of both phages. Apparently, phage 2851 integrates at a different chromosomal locus than Stx2 phage 933W and Stx1 phage H19 in
E. coli
, explaining why Stx2c is often found in combination with Stx1 or Stx2 in
E. coli
O157 strains. Diagnostic PCR was performed to determine gene sequences specific for phage 2851 in wild-type
E. coli
O157 strains producing Stx2c. The phage 2851
q
and
o
genes were frequently detected in Stx2c-producing
E
.
coli
O157 strains, indicating that phages related to 2851 are associated with Stx2c production in strains of
E. coli
O157 that were isolated in different locations and time periods.