bluuebunny/crossref_metadata_2025 huggingface dataset:
Spin-wave study of the magnetization reversal in bilayered stripes
Authors: Chérif S. M. , Roussigné Y. , Moch P. , Sergeeva N. A.
Published: September 2005

The magnetization reversal in Fe∕Au∕Fe bilayered ferromagnetic stripes is studied through Brillouin light-scattering measurements of the spin-wave behavior. Using a simplified model for the magnetic energy we find four available equilibrium magnetic configurations in the case of a magnetic field H applied along the stripe; their stability depends on the value of H. This dependence is formulated as a function of geometrical parameters and of the interlayer coupling. Our spectroscopical results allow us to evidence two critical coercitive fields Hmc and HMc(Hmc<HMc) which, as expected, do not exceed the calculated saturation fields defining the considered configurations. They suggest a composite multidomain structure within the [Hmc,HMc] interval and a conventional alignment along the field outside of this interval. The spin-wave frequencies are calculated for the four possible cases and compared to our Brillouin data.
Interfaces in GaxIn1−xAsySb1−y∕AlxGa1−xAsySb1−y multi-quantum-well heterostructures probed by transmittance anisotropy spectroscopy
Authors: Cerda-Méndez E. A. , Balderas-Navarro R. E. , Lastras-Martínez A. , Lastras-Martínez L. F. , Garnache A. , Cerutti L. , Jouillé A.
Published: September 2005

We have used transmission anisotropy (TA) and photoreflectance-difference (PRD) spectroscopies as tools for the characterization of heterostructures consisting of 100Å GaxIn1−xAsySb1−y quantum wells with 200Å AlxGa1−xAsySb1−y barriers. Exctions associated to two allowed and two forbidden transitions of the confined levels in the quantum wells (QWs) are detected with PRD at 15K. Using TA spectroscopy they all can be clearly resolved at room temperature. The signal of the anisotropy is proved experimentally to stem exclusively from the QWs and the surrounding interfaces. We show TA spectroscopy to be a powerful tool for interface characterization in heterostructures with energy gap below that of the substrate.
On steady solutions of symmetry-preserving perturbations of the two-dimensional Couette flow problem
Authors: Mehta P. G. , Healey T. J.
Published: September 2005

We discuss homotopy methods for obtaining two-dimensional (2D) steady solutions of the planar Couette flow problem together with the relationship of these solutions to the spectrum of its linearization and to the symmetry of the nonlinear problem. In order to obtain these solutions, we classify the near-degeneracy of the real part of the spectrum, construct a certain homotopy that preserves the symmetry of the nonlinear problem, and propose fixed-point space computations to compute these solutions. We obtain numerical solutions for extremely small symmetry-preserving perturbations of the nonlinear equations governing 2D Couette flow.
Influence of nonmagnetic Al ions on magnetoresistance of double-perovskite Sr2Fe1−xAlxMoO6 (0≤x≤0.30)
Authors: Sui Yu , Wang Xianjie , Cheng Jinguang , Liu Zhiguo , Miao Jipeng , Huang Xiqiang , Lu Zhe , Qian Zhengnan , Su Wenhui , Tang Jinke , Ong C. K.
Published: September 2005

The structural, magnetic, and magnetoresistance properties of the double-perovskite series Sr2Fe1−xAlxMoO6 (0≤x≤0.30) were systematically investigated in order to clarify the influence of nonmagnetic Al ions on the magnetoresistance. The structural refinements of these samples show that the degree of cationic order increases gradually from 88.5% for x=0 to 92% for x=0.30 without any change in the crystal structure. The magnetization measurements reveal that the substitution of nonmagnetic Al ion for Fe ion enhances the magnetic moment per Fe ion significantly. In addition, the magnetic-field dependence of magnetization and magnetoresistance of these Sr2Fe1−xAlxMoO6 samples were all fitted excellently by taking into account the contributions from ferromagnetic-coupled Fe–O–Mo region and nonferromagnetic-coupled regions. The fitting results indicate that the low-field magnetoresistance can be greatly enhanced due to the separation of the cationic-ordered Fe–O–Mo regions by the paramagnetic Mo–O–Al–O–Mo chains introduced through Al doping. Furthermore, doping nonmagnetic Al ions also suppress the formation of antiferromagnetic Fe–O–Fe antiphase boundaries, and then lead to the improvement of cation ordering and the reduction of magnetoresistance under high field.
The strength of diamond
Authors: Eremets Mikhail I. , Trojan Ivan A. , Gwaze Patience , Huth Joachim , Boehler Reinhard , Blank Vladimir D.
Published: September 2005

Diamond is the hardest known material; however, its mechanical stability, in particular the yield strength σy, is not known. We report reproducible generation of plastic deformation of diamond at room and low temperatures. We determined σy=130–140GPa by measuring the pressure distribution over the diamond anvils and by using the theory of elasticity. Yielding in diamond is accompanied by a strong luminescence with a characteristic spectrum. Our findings may be used to extend the static pressure limit beyond the current value of about 300GPa(3Megabars).
Adaptation of flexible polymer fabrication to cellular mechanics study
Authors: Zhao Yi , Zhang Xin
Published: September 2005

Polymeric material has been utilized as mechanical sensors to measure microscopic cellular forces. Since many polymers are not readily compatible with conventional lithography, fabrication of numerous molds is inevitably a part of the process, compromising low cost and process simplicity. In this letter, we apply a flexible fabrication process to manufacture polymeric mechanical sensors with various aspect ratios from a single rigid mold. A proof-of-principle measurement was carried out in isolated cardiac myocytes. The results conform to the physiologic behavior. This approach has the potential for evaluation of mechanical interaction between various biological units and the substrates while minimizing the fabrication cost and complexity.
Effect of doping concentration on the performance of terahertz quantum-cascade lasers
Authors: Liu H. C. , Wächter M. , Ban D. , Wasilewski Z. R. , Buchanan M. , Aers G. C. , Cao J. C. , Feng S. L. , Williams B. S. , Hu Q.
Published: September 2005

We characterized a set of terahertz quantum-cascade lasers with identical device parameters except for the doping concentration. The δ-doping density was varied from 3.2×1010to4.8×1010cm−2. We observed that the threshold current density increased monotonically with doping. Moreover, the measured results on devices with different cavity lengths provided evidence that the free carrier absorption caused waveguide loss also increased monotonically. Interestingly, however, the observed maximum lasing temperature displayed an optimum at a doping density of 3.6×1010cm−2.
Band-gap control optical Kerr effect and light self-focusing of semiconducting materials CdxHg1−xGa2S4
Authors: Cheng W.-D. , Huang S.-P. , Wu D.-S. , Li X.-D. , Lan Y.-Z. , Li F.-F. , Shen J. , Zhang H. , Gong Y.-J.
Published: September 2005

We report the dispersion of the optical Kerr effect and the wavelength-dependent critical power of light self-focusing for semiconductors CdxHg1−xGa2S4 in view of the calculated results from the density functional theory combined with an anharmonic oscillator model. It is shown that the third-order optical properties are controlled by the band gaps or cation contents of CdxHg1−xGa2S4, and it is indicated that the optical Kerr effect decreases and the critical power of light self-focusing increases as the x contents and band gaps increase for CdxHg1−xGa2S4.
Synthesis and characterization of quasi-aligned ZnCdO nanorods
Authors: Wang F. Z. , Ye Z. Z. , Ma D. W. , Zhu L. P. , Zhuge F. , He H. P.
Published: September 2005

Quasi-aligned ZnCdO single-crystal nanorods were prepared for the first time by using thermal evaporation of Zn and CdCl2 on a Si substrate with the presence of Au catalyst. The maximum Cd content was up to about 16.7at.%, which was significantly larger than the thermodynamic solid solubility limits. The ZnCdO nanorods have uniform flat hexagonal crystallographic planes with diameters of about 150nm. Notably, with the Cd content increasing, the ultraviolet near-band-edge emission was redshifted to 407nm(3.04eV) from 386nm(3.21eV). The direct modulation of the band gap caused by Cd substitution is responsible for the redshift. The possible growth mechanism of the ZnCdO nanorods was discussed.
Synthesis and ferroelectric properties of multiferroic BiFeO3 nanotube arrays
Authors: Zhang X. Y. , Lai C. W. , Zhao X. , Wang D. Y. , Dai J. Y.
Published: September 2005

We report the synthesis and characterization of ordered multiferroic BiFeO3 (BFO) nanotube arrays. BFO nanotubes with diameters of about 250nm and lengths of about 6μm were fabricated by means of a sol-gel method utilizing nanochannel alumina templates. After postannealing at 700°C, the BFO nanotubes exhibited a polycrystalline microstructure, and x-ray diffraction and transmission electron microscopy study revealed that they are of a perovskite crystal structure. Significant ferroelectric and piezoelectric characteristics of BFO nanotubes have been demonstrated by means of piezoresponse force microscopy measurement.
Effect of AlN interlayers on growth stress in GaN layers deposited on (111) Si
Authors: Raghavan Srinivasan , Weng Xiaojun , Dickey Elizabeth , Redwing Joan M.
Published: September 2005

Thin (∼10nm) AlN interlayers have previously been used to mitigate stress and cracking in GaN epitaxial layers grown on Si substrates. However, multiple AlN interlayers are typically required for the growth of thick (>1μm) GaN as the initial compressive mismatch stress introduced by the AlN interlayer transitions to a tensile stress within 0.5μm. To better understand the reasons for the transition, in situ monitoring and transmission electron microscopy have been used to study stress and structural evolution in undoped GaN layers deposited on high temperature (1050–1100°C) AlN interlayers by metal-organic chemical-vapor deposition. The results show that transition of the initial compressive stress to a final tensile stress is associated with a reduction in the density of dislocations introduced either by the pseudosubstrate or the interlayer itself.
Rapid directional shift of mitochondrial DNA heteroplasmy in animal tissues by a mitochondrially targeted restriction endonuclease
Authors: Bayona-Bafaluy Maria Pilar , Blits Bas , Battersby Brendan J. , Shoubridge Eric A. , Moraes Carlos T.
Published: September 2005

Frequently, mtDNA with pathogenic mutations coexist with wild-type genomes (mtDNA heteroplasmy). Mitochondrial dysfunction and disease ensue only when the proportion of mutated mtDNAs is high, thus a reduction in this proportion should provide an effective therapy for these disorders. We developed a system to decrease specific mtDNA haplotypes by expressing a mitochondrially targeted restriction endonuclease, ApaLI, in cells of heteroplasmic mice. These mice have two mtDNA haplotypes, of which only one contains an ApaLI site. After transfection of cultured hepatocytes with mitochondrially targeted ApaLI, we found a rapid, directional, and complete shift in mtDNA heteroplasmy (2-6 h). We tested the efficacy of this approach
in vivo
, by using recombinant viral vectors expressing the mitochondrially targeted ApaLI. We observed a significant shift in mtDNA heteroplasmy in muscle and brain transduced with recombinant viruses. This strategy could prevent disease onset or reverse clinical symptoms in patients harboring certain heteroplasmic pathogenic mutations in mtDNA.
Expression of DNA polymerase β cancer-associated variants in mouse cells results in cellular transformation
Authors: Sweasy Joann B. , Lang Tieming , Starcevic Daniela , Sun Ka-Wai , Lai Char-Chang , DiMaio Daniel , Dalal Shibani
Published: September 2005

Thirty percent of the 189 tumors studied to date express DNA polymerase β variants. One of these variants was identified in a prostate carcinoma and is altered from isoleucine to methionine at position 260, within the hydrophobic hinge region of the protein. Another variant was identified in a colon carcinoma and is altered at position 289 from lysine to methionine, within helix N of the protein. We have shown that the types of mutations induced by these cancer-associated variants are different from those induced by the wild-type enzyme. In this study, we show that expression of the I260M and K289M cancer-associated variants in mouse C127 cells results in a transformed phenotype in the great majority of cell clones tested, as assessed by focus formation and anchorage-independent growth. Strikingly, cellular transformation occurs after a variable number of passages in culture but, once established, does not require continuous expression of the polymerase β variant proteins, implying that it has a mutational basis. Because DNA polymerase β functions in base excision repair, our results suggest that mutations that arise during this process can lead to the onset or progression of cancer.
Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage
Authors: Monaco Lucia , Kolthur-Seetharam Ullas , Loury Romain , Murcia Josiane Ménissier-de , de Murcia Gilbert , Sassone-Corsi Paolo
Published: September 2005

The cell cycle-regulated Aurora-B kinase is a chromosomal passenger protein that is implicated in fundamental mitotic events, including chromosome alignment and segregation and spindle checkpoint function. Aurora-B phosphorylates serine 10 of histone H3, a function that has been associated with mitotic chromatin condensation. We find that activation of poly(ADP-ribose) polymerase (PARP) 1 by DNA damage results in a rapid block of H3 phosphorylation. PARP-1 is a NAD
+
-dependent enzyme that plays a multifunctional role in DNA damage detection and repair and maintenance of genomic stability. Here, we show that Aurora-B physically and specifically associates with the BRCT (BRCA-1 C-terminal) domain of PARP-1. Aurora-B becomes highly poly(ADP-ribosyl)ated in response to DNA damage, a modification that leads to a striking inhibition of its kinase activity. The highly similar Aurora-A kinase is not regulated by PARP-1. We propose that the specific inhibition of Aurora-B kinase activity by PARP-1 contributes to the physiological response to DNA damage.
Unified description of temperature-dependent hydrogen-bond rearrangements in liquid water
Authors: Smith Jared D. , Cappa Christopher D. , Wilson Kevin R. , Cohen Ronald C. , Geissler Phillip L. , Saykally Richard J.
Published: September 2005

The unique chemical and physical properties of liquid water are a direct result of its highly directional hydrogen-bond (HB) network structure and associated dynamics. However, despite intense experimental and theoretical scrutiny spanning more than four decades, a coherent description of this HB network remains elusive. The essential question of whether continuum or multicomponent (“intact,” “broken bond,” etc.) models best describe the HB interactions in liquid water has engendered particularly intense discussion. Most notably, the temperature dependence of water's Raman spectrum has long been considered to be among the strongest evidence for a multicomponent distribution. Using a combined experimental and theoretical approach, we show here that many of the features of the Raman spectrum that are considered to be hallmarks of a multistate system, including the asymmetric band profile, the isosbestic (temperature invariant) point, and van't Hoff behavior, actually result from a continuous distribution. Furthermore, the excellent agreement between our newly remeasured Raman spectra and our model system further supports the locally tetrahedral description of liquid water, which has recently been called into question [Wernet, P.,
et al.
(2004)
Science
304, 995-999].
Insulin as a Primary Autoantigen for Type 1A Diabetes
Authors: Jasinski J. M. , Eisenbarth G. S.
Published: September 2005

Type 1A diabetes mellitus is caused by specific and progressive autoimmune
destruction of the beta cells in the islets of Langerhans whereas the other cell
types in the islet (alpha, delta, and PP) are spared. The autoantigens of Type
1A diabetes may be divided into subgroups based on their tissue distributions:
Beta‐cell‐specific antigens like insulin, insulin derivatives, and IGRP (Islet‐specific
Glucose‐6‐phosphatase catalytic subunit Related Peptide); neurendocrine antigens
such as carboxypeptidase H, insulinoma‐associated antigen (IA‐2), glutamic acid
decarboxylase (GAD65), and carboxypeptidase E; and those expressed
ubiquitously like heat shock protein 60 (a putative autoantigen for type 1 diabetes).
This review will focus specifically on insulin as a primary autoantigen, an essentia
l target for disease, in type 1A diabetes mellitus. In particular, immunization with
insulin peptide B:9‐23 can be used to induce insulin autoantibodies and diabetes
in animal models or used to prevent diabetes. Genetic manipulation of the insulin
1 and 2 genes reciprocally alters development of diabetes in the NOD mouse,
and insulin gene polymorphisms are important determinants of childhood
diabetes. We are pursuing the hypothesis that insulin is a primary autoantigen
for type 1 diabetes, and thus the
pathogenesis of the disease relates to specific recognition of one or more peptides.
Application of a Static Fluorescence‐based Cytometer (the CellScan) in Basic Cytometric Studies, Clinical Pharmacology, Oncology and Clinical Immunology
Authors: Harel Michal , Gilburd Boris , Schiffenbauer Yael S. , Shoenfeld Yehuda
Published: September 2005

The CellScan apparatus is a laser scanning cytometer enabling repetitive
fluorescence intensity (FI) and polarization (FP) measurements in living cells, as
a means of monitoring lymphocyte activation. The CellScan may serve as a tool for
diagnosis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) as
well as other autoimmune diseases by monitoring FP changes in peripheral blood
lymphocytes (PBLs) following exposure to autoantigenic stimuli. Changes in FI and
FP in atherosclerotic patients′ PBLs following exposure to various stimuli have
established the role of the immune system in atherosclerotic disease. The CellScan
has been evaluated as a diagnostic tool for drug‐allergy, based on FP reduction in
PBLs following incubation with allergenic drugs. FI and FP changes in cancer cells
have been found to be well correlated with the cytotoxic effect of anti‐neoplastic
drugs. In conclusion, the CellScan has a variety of
applications in cell biology, immunology, cancer research and clinical pharmacology.
Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis
Authors: Ferenčík Miroslav , štvrtinová Viera , Hulín Ivan
Published: September 2005

Atherosclerosis is nowadays generally accepted as an inflammatory disease
but the mechanism of its origin and development have not yet been fully clarified.
The present review focuses on the role of the local immune system as one of the
key players in the pathogenesis of the complex process. Its part represented by
vascular‐associated lymphoid tissue (VALT) within the arterial wall participates
directly in the vascular wall′s homeostatis. Its inordinate activation during
ontogenic development of an individual, this formerly defensive and physiologic
mechanism transform into a pathological process resulting in an impairing
inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious
candidates for triggering these pathological changes. The principal role is played
by anti‐Hsp60 antibodies and by shear stress originating on the surface of
endothelium due to blood flow. The experimental and clinical data
supporting this immunological hypothesis of atherosclerosis are discussed.
Unique Gene Expression Patterns in Human T‐cell Lines Generated from Multiple Sclerosis Patients by Stimulation with a Synthetic MOG Peptide
Authors: Mandel Mathilda , Gurevich Michael , Lavie Gad , Cohen Irun R. , Achiron Anat
Published: September 2005

Multiple sclerosis (MS) is an autoimmune disease where T‐cells activated
against myelin antigens are involved in myelin destruction. Yet, healthy subjects
also harbor T‐cells responsive to myelin antigens, suggesting that MS
patient‐derived autoimmune T‐cells might bear functional differences from
T‐cells derived from healthy individuals. We addressed this issue by analyzing
gene expression patterns of myelin oligodendrocytic glycoprotein (MOG)
responsive T‐cell lines generated from MS patients and healthy subjects. We
identified 150 transcripts that were differentially expressed between MS patients
and healthy controls. The most informative 43 genes exhibited >1.5‐fold change
in expression level. Eighteen genes were up‐regulated including BCL2, lifeguard,
IGFBP3 and VEGF. Twenty five genes were down‐regulated, including apoptotic
activators like TNF and heat shock protein genes. This gene expression pattern
was unique to MOG specific T‐cell lines and was not expressed in T‐cell lines
reactive to tetanus toxin (TTX). Our results indicate that activation in MS that
promotes T‐cell survival and expansion, has its own state and that the unique gene
expression pattern that characterize autoreactive T‐cells in MS represent
a constellation of factors in which the chronicity, timing
and accumulation of damage make the difference between health and disease.
A Study of Molecular Mimicry and Immunological Cross‐reactivity between Hepatitis B Surface Antigen and Myelin Mimics
Authors: Bogdanos Dimitrios-Petrou , Smith Heather , Ma Yun , Baum Harold , Mieli-Vergani Giorgina , Vergani Diego
Published: September 2005

On the basis of the reported association between hepatitis B vaccination
(HBvacc) and autoimmune demyelinating complications such as multiple sclerosis
(MS), we have looked for aminoacid similarities between the small hepatitis
B virus surface antigen (SHBsAg), and the MS‐autoantigens myelin basic protein
(MBP) and myelin oligodendrocyte glycoprotein (MOG) that could serve as targets
of immunological cross‐reactivity. Twenty‐mer peptides spanning 4 SHBsAg/MOG
and 1 SHBsAg/MBP mimicking pairs, were constructed and tested by ELISA as
targets of cross‐reactive responses. A total of 147 samples from 58 adults were
collected before HBvacc (58/58), and post‐HBvacc (48/58 before the second and
41/58 before the third boost). Eighty‐seven sera from anti‐SHBsAg antibody
negative patients with various diseases were tested as pathological controls.
Reactivity to at least one of the SHBsAg peptides was found in 8 (14%)
pre‐HBvacc subjects; amongst the remaining 50, reactivity to at least one of the
SHBsAg peptides appeared in 47 (94%) post‐HBvacc. Reactivity to at least one
of the MOG mimics was present in 4 (8%) pre‐HBvacc and in 30 (60%)
post‐HBvacc (p < 0.001). Overall 30/50 (60%) vaccinees had SHBsAg/MOG
double reactivity on at least one occasion compared to none before‐vaccination
and in 2 (2%) of the pathological controls (p < 0.001 for both). SHBsAg/MOG
double reactivity was cross‐reactive as confirmed by inhibition studies. At 6 months
post‐vaccination, 3 of the 4 anti‐MOG reactive cases before vaccination and 7
of the 24 (29%) of the anti‐MOG reactive cases at 3 months post‐vaccination had
lost their reactivity to MOG5-24. There was no reactivity to the SHBsAg/MBP
mimics. None of the vaccinees reported symptoms of demyelinating disorders. In
view of the observed SHBsAg/MOG cross‐reactivity, the vaccine′s possible role as
an immunomodulator of viral/self cross‐reactivity must be further investigated.
Implicit learning of a repeated segment in continuous tracking: A reappraisal
Authors: Chambaron Stephanie , Ginhac Dominique , Ferrel-Chapus Carole , Perruchet Pierre
Published: September 2005

Several prior studies (e.g., Shea, Wulf, Whitacre, & Park, 2001; Wulf & Schmidt, 1997) have apparently demonstrated implicit learning of a repeated segment in continuous-tracking tasks. In two conceptual replications of these studies, we failed to reproduce the original findings. However, these findings were reproduced in a third experiment, in which we used the same repeated segment as that used in the Wulf et al. studies. Analyses of the velocity and the acceleration of the target suggests that this repeated segment could be easier to track than the random segments serving as control, accounting for the results of Wulf and collaborators. Overall these experiments suggest that learning a repeated segment in continuous-tracking tasks may be much more difficult than learning from a repeated sequence in conventional serial reaction time tasks. A possible explanation for this difference is outlined.
Compartmentalization of class II antigen presentation: contribution of cytoplasmic and endosomal processing
Authors: Li Ping , Gregg Josetta L. , Wang Nan , Zhou Delu , O'Donnell Patrick , Blum Janice S. , Crotzer Victoria L.
Published: September 2005

Summary:  During antigen processing, peptides are generated and displayed in the context of major histocompatibility complex (MHC) class II molecules on the surface of antigen‐presenting cells (APCs) to modulate immune responses to foreign antigens and guide self‐tolerance. Exogenous and cytoplasmic antigens are processed by distinct routes within APCs to yield class II ligands. Exogenous antigens are internalized, processed, and bound to class II molecules within endosomal and lysosomal compartments of APCs. Studies reviewed here demonstrate the importance of reduction in regulating exogenous antigen presentation. The differential expression of a γ‐interferon‐inducible lysosomal thiol reductase in professional APCs and melanomas is discussed in the context of tumor immune evasion. Cytoplasmic autoantigens, by contrast, are degraded by the proteasome and other enzymes in the cytosol, with the resulting peptides translocating to endosomal and lysosomal compartments for intersection with class II molecules. Processing and editing of these antigenic peptides within endosomes and lysosomes may be critical in regulating their display via class II proteins. Multiple pathways may regulate the transit of cytosolic peptides to class II molecules. The role of lysosome‐associated membrane protein‐2a and heat‐shock cognate protein 70 in promoting cytoplasmic peptide presentation by MHC class II molecules is discussed.
Dendritic cells, DRiPs, and DALIS in the control of antigen processing
Authors: Pierre Philippe
Published: September 2005

Summary:  The study of the cell biology of antigen processing and presentation has greatly contributed to our understanding of the immune response. The work of many immunologically inclined cell biologists has also permitted new insights into cellular mechanisms shared by many cell types. Here are described recent and particularly exciting findings on the regulation of major histocompatibility complex class I‐restricted presentation in dendritic cells and their contribution to the deciphering of the cellular response to pathogen detection.
Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression
Authors: Busch Robert , Rinderknecht Cornelia H. , Roh Sujin , Lee Andrew W. , Harding James J. , Burster Timo , Hornell Tara M. C. , Mellins Elizabeth D.
Published: September 2005

Summary:  In antigen‐presenting cells (APCs), loading of major histocompatibility complex class II (MHC II) molecules with peptides is regulated by invariant chain (Ii), which blocks MHC II antigen‐binding sites in pre‐endosomal compartments. Several molecules then act upon MHC II molecules in endosomes to facilitate peptide loading: Ii‐degrading proteases, the peptide exchange factor, human leukocyte antigen‐DM (HLA‐DM), and its modulator, HLA‐DO (DO). Here, we review our findings arguing that DM stabilizes a globally altered conformation of the antigen‐binding groove by binding to a lateral surface of the MHC II molecule. Our data imply changes in the interactions between specificity pockets and peptide side chains, complementing data from others that suggest DM affects hydrogen bonds. Selective weakening of peptide/MHC interactions allows DM to alter the peptide repertoire. We also review our studies in cells that highlight the ability of several factors to modulate surface expression of MHC II molecules via post‐Golgi mechanisms; these factors include MHC class II‐associated Ii peptides (CLIP), DM, and microbial products that modulate MHC II traffic from endosomes to the plasma membrane. In this context, we discuss possible mechanisms by which the association of some MHC II alleles with autoimmune diseases may be linked to their low CLIP affinity.
The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes
Authors: Sant Andrea J. , Chaves Francisco A. , Jenks Scott A. , Richards Katherine A. , Menges Paula , Weaver J. M. , Lazarski Christopher A.
Published: September 2005

Summary:  Immunodominance refers to the restricted antigen specificity of T cells detected in the immune response after immunization with complex antigens. Despite the presence of many potential peptide epitopes within these immunogens, the elicited T‐cell response apparently focuses on a very limited number of peptides. Over the last two decades, a number of distinct explanations have been put forth to explain this very restricted specificity of T cells, many of which suggest that endosomal antigen processing restricts the array of peptides available to recruit CD4 T cells. In this review, we present evidence from our laboratory that suggest that immunodominance in CD4 T‐cell responses is primarily due to an intrinsic property of the peptide:class II complexes. The intrinsic kinetic stability of peptide:class II complexes controls DM editing within the antigen‐presenting cells and thus the initial epitope density on priming dendritic cells. Additionally, we hypothesize that peptides that possess high kinetic stability interactions with class II molecules display persistence at the cell surface over time and will more efficiently promote T‐cell signaling and differentiation than competing, lower‐stability peptides contained within the antigen. We discuss this model in the context of the existing data in the field of immunodominance.
The seven dirty little secrets of major histocompatibility complex class I antigen processing
Authors: W. Yewdell Jonathan
Published: September 2005

Summary:  Every field has its dirty little secrets (DLSs): assumptions based on flimsy evidence, findings that directly contradict prevailing models or so beg comprehension that they cannot even seed reasonable alternative hypotheses. Although our natural tendency is to hug these DLSs, they should be exposed, for it is these gaps in our understanding that point to the path to enlightenment. Here, I discuss some of the DLSs of major histocompatibility complex class I antigen processing.
The lysosomal cysteine proteases in MHC class II antigen presentation
Authors: Hsing Lianne C. , Rudensky Alexander Y.
Published: September 2005

Summary:  The endosomal pathway of antigen presentation leads to the display of peptides on major histocompatibility complex (MHC) class II molecules at the cell surface of antigen‐presenting cells (APCs). The pathway involves two major steps, invariant chain degradation and antigen processing, which take place in the late endosomes/lysosomes. So far, of the known lysosomal proteases, only cathepsin L and cathepsin S have been shown to have a non‐redundant role in endosomal presentation in vivo. Besides being engaged in the degradation of invariant chain, these enzymes also mediate the processing of antigens in distinct cell types. Surprisingly, these enzymes are active in different types of APCs, and this defined expression pattern seems to be enforced by regulatory mechanisms acting on multiple levels.
The optimization of peptide cargo bound to MHC class I molecules by the peptide‐loading complex
Authors: Elliott Tim , Williams Anthony
Published: September 2005

Summary:  Major histocompatibility complex (MHC) class I complexes present peptides from both self and foreign intracellular proteins on the surface of most nucleated cells. The assembled heterotrimeric complexes consist of a polymorphic glycosylated heavy chain, non‐polymorphic β2 microglobulin, and a peptide of typically nine amino acids in length. Assembly of the class I complexes occurs in the endoplasmic reticulum and is assisted by a number of chaperone molecules. A multimolecular unit termed the peptide‐loading complex (PLC) is integral to this process. The PLC contains a peptide transporter (transporter associated with antigen processing), a thiooxido‐reductase (ERp57), a glycoprotein chaperone (calreticulin), and tapasin, a class I‐specific chaperone. We suggest that class I assembly involves a process of optimization where the peptide cargo of the complex is edited by the PLC. Furthermore, this selective peptide loading is biased toward peptides that have a longer off‐rate from the assembled complex. We suggest that tapasin is the key chaperone that directs this action of the PLC with secondary contributions from calreticulin and possibly ERp57. We provide a framework model for how this may operate at the molecular level and draw parallels with the proposed mechanism of action of human leukocyte antigen‐DM for MHC class II complex optimization.
Asparaginyl endopeptidase: case history of a class II MHC compartment protease
Authors: Watts Colin , Matthews Stephen P. , Mazzeo Daniela , Manoury Bénédicte , Moss Cathy X.
Published: September 2005

Summary: Although the endpoint of the class II antigen‐processing pathway is well characterized, the processing events that lead to the production of class II major histocompatibility complex (MHC)/peptide complexes are not. It is generally assumed that protease action on native antigen substrates leads to unfolding and capture of either long or short peptides. Whether specific protease activities are needed for presentation of particular T‐cell epitopes is largely unknown. Here, we review our recent studies that aim to identify the processing enzymes that initiate processing of different antigens. We suggest a general strategy that can potentially identify preferred relationships between substrates and processing enzymesin vitro and suggest ways in which these relationships can be testedin vivo. We draw heavily on the example of asparaginyl endopeptidase, which is involved in both productive and destructive processing of different antigen substrates. Overall, while there is undoubtedly redundancy in class II MHC antigen processing, the contributions of individual enzymes can be clearly dissected.
Mechanisms of MHC class I‐restricted antigen processing and cross‐presentation
Authors: Cresswell Peter , Ackerman Anne L. , Giodini Alessandra , Peaper David R. , Wearsch Pamela A.
Published: September 2005

Summary:  In this review, we discuss recent data from our laboratory that address two aspects of major histocompatibility complex (MHC) class I‐restricted antigen processing. First, we consider the nature of the peptide‐loading complex, which is the assembly of proteins in the endoplasmic reticulum (ER) into which newly synthesized MHC class I‐β2 microglobulin (β2m) heterodimers are incorporated, and the mechanisms involved in MHC class I assembly and peptide loading that are facilitated by the peptide‐loading complex. Second, we discuss mechanisms of cross‐presentation, the phenomenon whereby extracellular and luminal protein antigens can be processed by antigen‐presenting cells, particularly dendritic cells, and presented by MHC class I molecules to CD8+ T cells. The focus of the discussion is mainly on the human MHC class I system.
Control of MHC class II antigen presentation in dendritic cells: a balance between creative and destructive forces
Authors: Villadangos José A. , Schnorrer Petra , Wilson Nicholas S.
Published: September 2005

Summary:  The antigen capturing and presenting abilities of dendritic cells (DCs) are developmentally regulated in a process known as maturation. During maturation, DCs increase several fold their surface expression of major histocompatibility complex class II (MHC II) molecules. This increase is accompanied with a dramatic change in localization of MHC II molecules, which are abundant in endosomal structures in immature DCs but located mostly on the plasma membrane in mature DCs. How these changes relate to antigen processing, generation of MHC II–peptide complexes, and trafficking of MHC II molecules, in the immature and mature states of DC development, has been a matter of debate. Here, we discuss the work carried out to characterize the biochemical and cell biological mechanisms that control MHC II antigen presentation in mouse and human DCs, and how these mechanisms relate to the function of the DC network in vivo. We conclude that the control checkpoints operate downstream of MHC II–peptide complex formation and expression on the plasma membrane, acting in accord with control of MHC II synthesis. Therefore, immature and mature DCs present antigens to T cells under steady state and inflammatory conditions. We advocate that the mechanisms regulating MHC II–peptide complex turnover should be emphasized as an important theme for future DC research.
Phagocytosis: the convoluted way from nutrition to adaptive immunity
Authors: Desjardins Michel , Houde Mathieu , Gagnon Etienne
Published: September 2005

Summary:  Phagocytosis, the process by which cells internalize large particulate materials from their milieu and sequester them in phagosomes, plays a role in a variety of cell functions ranging from nutrition in ameba to innate and adaptive immunity in mammals. Recent findings revealed unexpected characteristics of phagosomes, highlighting how this complex organelle may have evolved, from Dictyostelium to human, to become a key player in our ability to mount an efficient immune response against a variety of intracellular pathogens.
Rayleigh Scattering in Silica Glasses
Authors: Sakaguchi Shigeki , Todoroki Shin‐ichi , Shibata Shuichi
Published: September 2005

Rayleigh‐scattering properties in commercial silica glasses is clarified with relation to their fabrication methods. Fused silica and synthetic silica made by the flame hydrolysis of SiCl4 (VAD) method exhibit similar magnitudes of scattering, regardless of fabrication method. Synthetic silica made by flame fusion of SiCl4 exhibits ∼10% lower scattering than other silica glasses. The factors affecting scattering are evaluated based on refractive index dispersion and glass transition temperature (Tg). The results suggest that the difference in Rayleigh scattering is predominantly attributable to the difference in Tg, which is affected by impurities, such as OH ions.
Short‐Range and Medium‐Range Order in Lithium Silicate Glasses, Part I: Diffraction Experiments and Results
Authors: Uhlig Harald , Hoffmann Michael J. , Lamparter Hannes‐Peter , Aldinger Fritz , Bellissent Robert , Steeb Siegfried
Published: September 2005

Silicate glasses of the composition (Li2O)x(SiO2)100−x (x= 0, 20, 33.3, and 40) have been prepared and characterized by X‐ray and neutron diffraction experiments using the technique of isotopic substitution. Thus, at each composition, a set of independent diffraction patterns allows the discussion of the short‐range and medium‐range structure. For the short‐range structure, average coordination numbers and atomic‐pair distances are obtained from the pairdistribution functions. For the medium‐range structure, i.e., for atomic‐pair distances >0.5 nm, an increase of the amplitudes of the oscillations in the pair‐distribution function is observed with increases in the Li2O content.
Polymerized Complex Route to Barium Titanate Powders Using Barium‐Titanium Mixed‐Metal Citric Acid Complex
Authors: Arima Momoko , Kakihana Masato , Nakamura Yoshiyuki , Yashima Masatomo , Yoshimura Masahiro
Published: September 2005

Barium titanate (BaTiO3) powders were prepared by a polymerized complex method based on the Pechini‐type reaction route, wherein a mixed solution of citric acid (CA), ethylene glycol (EG), and barium and titanium ions, with a molar ratio of CA:EG:Ba:Ti = 10:40:1:1, was polymerized to form a transparent resin, which was used as a precursor for BaTiO3. Characterization of the initial precursor solution of EG, CA, and barium and titanium ions by Raman scattering and 13C‐NMR spectroscopy indicated that barium and titanium ions were simultaneously stabilized with CA to form a barium‐titanium mixed‐metal CA complex with a stoichiometry similar to Ba:Ti:CA = 1:1:3. Raman and 13C‐NMR spectra of the liquid mixture at various reaction stages indicated that the fundamental coordination structure of the mixed‐metal complex remained almost unchanged throughout the polymerization process. X‐ray diffractometry (XRD) measurements indicated formation of pseudo‐cubic BaTiO3 free from BaCO3 and TiO2 when the barium‐titanium polymeric precursor was heat‐treated in air at 500°C for 8 h or at 600°C for 2 h. However, the Raman spectra of the same powders indicated the formation of tetragonal (rather than cubic) BaTiO3, with traces of high‐temperature hexagonal BaTiO3 stabilized at room temperature. XRD of a pyrolyzed product at 500°C for 2 h revealed a simple mixture of BaTiO3 and an intermediate phase, Ba2Ti2O5.CO3. A solid‐state reaction between BaCO3 and TiO2 was concluded as not being responsible for the BaTiO3 formation; rather, BaTiO3 formed directly by thermal decomposition of the intermediate Ba2Ti2O5.CO3 phase at temperatures >500°C. In addition, by Raman scattering measurements, the intermediate Ba2Ti2O5.CO3 phase was found to be unstable in ambient air, yielding BaCO3 as one of the decomposed products.
Thermal Shock Damage in a Two‐Dimensional Woven‐Fiber‐Reinforced‐CVI SiC‐Matrix Composite
Authors: Webb James E. , Singh Raj N. , Lowden Richard A.
Published: September 2005

Thermal shock damage in a two‐dimensional woven‐Nicalon(tm)‐fiber‐reinforced‐CVI SiC‐matrix composite was induced by water quenching and characterized by optical microscopy as a function of quench temperature difference (ΔT) and number of quench cycles. Mechanical damage generated in flexure on quenched and unquenched specimens also was characterized and compared to the thermal shock damage. The observed thermal shock damage consisted of small matrix cracks and fiber‐matrix interfacial debonding on the surface, and large interior cracks in the matrix that formed between and parallel to the fiber cloths. At low ΔT values, only small matrix cracks on the surface were observed, and they were related to initial decreases in Young's modulus. At higher ΔT values, larger cracks between the fiber cloths in the specimen interior were observed and related to decreases in the ultimate strength. Cyclic quenching resulted in progressive thermal shock damage that was consistent with Young's modulus measurements.
Synthesis of Oxynitride Powders via Fluidized‐Bed Ammonolysis, Part I: Large, Porous, Silica Particles
Authors: Bickmore Clint R. , Laine Richard M.
Published: September 2005

Reaction of silica (SiO2) with triethanolamine (TEA, N(CH2CH2OH)3) and ethylene glycol (EG) under conditions (∼200°C) where byproduct water is removed resulted in the formation of the neutral silatrane glycolate complex, N(CH2CH2O)3SiOCH2CH2OH (or TEASiOCH2CH2OH) in essentially quantitative yield. Solutions of this neutral precursor in EG, when rapidly pyrolyzed and then oxidized at 500°C, formed porous ceramic powders with high specific surface areas (>500 m2/g). These powders were nitrided via ammonolysis in a fluidized‐bed reactor at temperatures of 700°‐1000°C. The resulting nitrided powders were characterized by thermal and chemical analyses, diffuse reflectance infrared spectroscopy, gas sorption, and X‐ray photoelectron spectroscopy. The apparent activation energy for the nitridation process was determined to be 54 kJ/mol. Following nitridation, the powders were amorphous and had nitrogen contents as high as 21 wt% with retained surface areas >300 m2/g at 1000°C. Under the nitridation conditions used, the extent of nitrogen incorporation correlated linearly with increases in material density. This linearity suggested that the change in density occurred primarily because of changes in coordination that occurred as trivalent nitrogen replaced divalent oxygen in the glass structure and nominally because of viscous flow. The linear density increase also suggested that pore trapping did not occur under these processing conditions. This work serves as a model for ongoing studies on the nitridation of high‐surface‐area ceramic powders produced by the rapid pyrolysis of mixed‐metal TEA alkoxides.
Σ5 (210)/[001] Symmetric Tilt Grain Boundary in Yttrium Aluminum Garnet
Authors: Campbell Geoffrey H.
Published: September 2005

The Σ5 (210)/[001] symmetric tilt grain boundary in yttrium aluminum garnet (YAG) was produced by diffusion bonding precisely oriented single crystals. The crystals were cleaned and bonded in an ultra‐high‐vacuum environment. The atomic structure of the boundary was characterized by high‐resolution transmission electron microscopy. Model atomic structures were created by geometric construction to form the coincident site lattice model boundary. Comparison of model structures with high‐resolution micrographs was performed by high‐resolution image simulation. Many aspects of the boundary structure were properly represented by the models, but some details of the high‐resolution images indicated that differences existed.
α→β Reverse Phase Transformation in Silicon Carbide in Silicon Nitride‐Particulate‐Reinforced‐Silicon Carbide Composites
Authors: Turan Servet , Knowles Kevin M.
Published: September 2005

The α→β reverse transformation in SiC is observed in Si3N4‐particulate‐reinforced‐SiC composites made from as‐received α‐SiC and α‐Si3N4 powders. However, the transformation does not occur to any great extent in composites made from deoxidized Si3N4‐SiC powder compacts. Detailed transmission electron microscopy shows that most interfaces are covered with an ∼10 Å thick amorphous intergranular film in the composites made from as‐received powders, whereas most interfaces are free of such films in the composites made from deoxidized powder compacts. These observations indicate that the α→β reverse transformation in SiC is encouraged by a nitrogen‐containing liquid phase that occurs at high temperature in the composites made from the as‐received powders. A mechanism is proposed to account for the experimental observations.
Formation of Pores and Y2BaCuO5‐Free Regions during Melt Processing of Y1.6 Ba2.3Cu3.3Ox
Authors: Lee Ho‐Yong , Kim Chan‐Joong , Hong Gye‐Won
Published: September 2005

The formation of spherical pores and regions free of Y2BaCuO5 (2‐1‐1) has been studied by melt processing Y1.6Ba2.3Cu3.3Ox: in two different atmospheres (air and oxygen). When the sintered Y1.6Ba2.3Cu3.3Ox specimens are melted at 1050°C, many spherical pores form in the melted specimens. During the subsequent cooling, the pores are filled by liquid flow and finally solidified to Y2BaCuO5‐free regions. Melt processing in an oxygen atmosphere produces more pores and regions free of 2‐1‐1 than in air. Because peritectic melting of YBa2Cu3O7‐y in an oxygen atmosphere produces more oxygen gas than that in air, the formation of the pores and Y2BaCuO5‐free regions is suggested to be attributed to the oxygen evolution during the peritectic melting of YBa2Cu3O7−y