bluuebunny/crossref_metadata_2025 huggingface dataset:
Speech recognition under conditions of frequency-place compression and expansion
Authors: Baskent Deniz , Shannon Robert V.
Published: March 2003

In normal acoustic hearing the mapping of acoustic frequency information onto the appropriate cochlear place is a natural biological function, but in cochlear implants it is controlled by the speech processor. The cochlear tonotopic range of the implant is determined by the length and insertion depth of the electrode array. Conventional cochlear implant electrode arrays are designed for an insertion of 25 mm inside the round window and the active electrodes occupy 16 mm, which would place the electrodes in a cochlear region corresponding to an acoustic frequency range of 500–6000 Hz. However, some implant speech processors map an acoustic frequency range from 150 to 10 000 Hz onto these electrodes. While this mapping preserves the entire range of acoustic frequency information, it also results in a compression of the tonotopic pattern of speech information delivered to the brain. The present study measured the effects of such a compression of frequency-to-place mapping on speech recognition using acoustic simulations. Also measured were the effects of an expansion of the frequency-to-place mapping, which produces an expanded representation of speech in the cochlea. Such an expanded representation might improve speech recognition by improving the relative spatial (tonotopic) resolution, like an “acoustic fovea.” Phoneme and sentence recognition was measured as a function of linear (in terms of cochlear distance) frequency-place compression and expansion. These conditions were presented to normal-hearing listeners using a noise-band vocoder, simulating cochlear implant electrodes with different insertion depths and different number of electrode channels. The cochlear tonotopic range was held constant by employing the same noise carrier bands for each condition, while the analysis frequency range was either compressed or expanded relative to the carrier frequency range. For each condition, the result was compared to that of the perfect frequency-place match, where the carrier and the analysis bands were perfectly matched. Speech recognition in the matched conditions was generally better than any condition of frequency-place expansion and compression, even when the matched condition eliminated a considerable amount of acoustic information. This result suggests that speech recognition, at least without training, is dependent on the mapping of acoustic frequency information onto the appropriate cochlear place.
Noise reduction in a launch vehicle fairing using actively tuned loudspeakers
Authors: Kemp Jonathan D. , Clark Robert L.
Published: March 2003

Loudspeakers tuned as optimal acoustic absorbers can significantly reduce damaging, low frequency, reverberant noise in a full-scale launch vehicle fairing. Irregular geometry, changing payloads, and the compliant nature of the fairing hinder effective implementation of a passively tuned loudspeaker. A method of tuning the loudspeaker dynamics in real time is required to meet the application requirements. Through system identification, the dynamics of the enclosure can be identified and used to tune the dynamics of the loudspeaker for reduction of targeted, high intensity, low-frequency modes that dominate the acoustic response in the fairing. A loudspeaker model with desired dynamics serves as the reference model in a control law designed to tune the dynamics of a non-ideal loudspeaker to act as an optimal tuned absorber. Experimental results indicate that a tuned loudspeaker placed in the nose cone of the fairing significantly reduces acoustic energy and verifies results calculated from the simulation.
Symmetrization of Ritz approximation functions for vibrational analysis of trigonal cylinders
Authors: Johnson Ward L. , Heyliger Paul R.
Published: March 2003

In the Ritz method of calculating vibrational normal modes, a set of finite series approximation functions provides a matrix eigenvalue equation for the coefficients in the series and the resonant frequency. The matrix problem usually can be block-diagonalized by grouping the functions into subsets according to their properties under the symmetry operations that are common to the specimen geometry and crystal class. This task is addressed, in this study, for the case of cylindrical specimens of crystals belonging to one of the higher trigonal crystal classes. The existence of doubly degenerate resonant modes significantly complicates the analysis. Group-theoretical projection operators are employed to extract, from series approximation functions in cylindrical coordinates, the terms that transform according to each irreducible representation of the point group. This provides a complete symmetry-based block diagonalization and categorization of the modal symmetries. Off-diagonal projection operators are used to provide relations between the displacement patterns of degenerate modes. The method of analysis is presented in detail to assist in its application to other geometries, crystal structures, and/or forms of Ritz approximation functions.
Speech transmission index from running speech: A neural network approach
Authors: Li F. F. , Cox T. J.
Published: March 2003

Speech transmission index (STI) is an important objective parameter concerning speech intelligibility for sound transmission channels. It is normally measured with specific test signals to ensure high accuracy and good repeatability. Measurement with running speech was previously proposed, but accuracy is compromised and hence applications limited. A new approach that uses artificial neural networks to accurately extract the STI from received running speech is developed in this paper. Neural networks are trained on a large set of transmitted speech examples with prior knowledge of the transmission channels’ STIs. The networks perform complicated nonlinear function mappings and spectral feature memorization to enable accurate objective parameter extraction from transmitted speech. Validations via simulations demonstrate the feasibility of this new method on a one-net-one-speech extract basis. In this case, accuracy is comparable with normal measurement methods. This provides an alternative to standard measurement techniques, and it is intended that the neural network method can facilitate occupied room acoustic measurements.
A practical method of predicting the loudness of complex electrical stimuli
Authors: McKay Colette M. , Henshall Katherine R. , Farrell Rebecca J. , McDermott Hugh J.
Published: March 2003

The output of speech processors for multiple-electrode cochlear implants consists of current waveforms with complex temporal and spatial patterns. The majority of existing processors output sequential biphasic current pulses. This paper describes a practical method of calculating loudness estimates for such stimuli, in addition to the relative loudness contributions from different cochlear regions. The method can be used either to manipulate the loudness or levels in existing processing strategies, or to control intensity cues in novel sound processing strategies. The method is based on a loudness model described by McKay et al. [J. Acoust. Soc. Am. 110, 1514–1524 (2001)] with the addition of the simplifying approximation that current pulses falling within a temporal integration window of several milliseconds’ duration contribute independently to the overall loudness of the stimulus. Three experiments were carried out with six implantees who use the CI24M device manufactured by Cochlear Ltd. The first experiment validated the simplifying assumption, and allowed loudness growth functions to be calculated for use in the loudness prediction method. The following experiments confirmed the accuracy of the method using multiple-electrode stimuli with various patterns of electrode locations and current levels.
Variation in chick-a-dee calls of a Carolina chickadee population,Poecile carolinensis: Identity and redundancy within note types
Authors: Freeberg Todd M. , Lucas Jeffrey R. , Clucas Barbara
Published: March 2003

Chick-a-dee calls of chickadee species are structurally complex because calls possess a rudimentary syntax governing the ordering of their different note types. Chick-a-dee calls were recorded in an aviary from female and male birds from two field sites. This paper reports sources of variation of acoustical parameters of notes in these calls. There were significant sex and microgeographic differences in some of the measured parameters of the notes in the calls. In addition, the syntax of the call itself influenced characteristics of each of the notes. For example, calls with many introductory notes began with a note of higher frequency and longer duration, relative to calls with few introductory notes. Furthermore, the number of introductory notes influenced frequency and duration components of notes later in the call. Thus, single notes are predictive of the note composition of the signaler’s call. This suggests that a receiver might gain the meaning in the call even if it hears only part of the call. Further, single notes within these complex calls can contain information enabling receivers to predict the sex of the signaler, and whether it is from the local population.
Investigations of the precedence effect in budgerigars: The perceived location of auditory images
Authors: Dent Micheal L. , Dooling Robert J.
Published: March 2003

The perceived location of auditory images has been recently studied in budgerigars [Dent and Dooling, J. Acoust. Soc. Am. 113, 2146–2158 (2003)]. Those results suggested that budgerigars (Melopsittacus undulatus) perceive precedence effect stimuli in a manner similar to humans and other animals. Here we extend those experiments to include the effects of intensity on the perceived location of auditory images and the perceived location of paired stimuli from multiple locations in space. We measured the abilities of budgerigars to discriminate between paired stimuli separated in time, intensity, and/or location. Increasing the intensity of a lag stimulus disrupted localization dominance. Budgerigars also perceived simultaneously presented (away from the midline) stimuli as very similar to a single sound presented from the midline, much like the phantom image reported in humans. The perception of paired stimuli from one side of the head versus two sides of the head was also examined and showed that the spatial cues available in these stimuli are important and that echoes are not perceptually inaccessible during localization dominance conditions. The results from these experiments add further data showing the precedence effect in budgerigars is similar to that found in humans and other animals.
Median plane localization: dependence on spectral content
Authors: Ng Gerald , Colburn H. Steven
Published: March 2003

Subjects were asked to report the elevation of noise stimuli differing in their spectral content. Some stimuli contained a single frequency band differing in center frequency and bandwidth; others contained multiple equal-amplitude frequency bands. All of the stimulus frequencies were in the range between 1 kHz and 16 kHz. Speakers were located in the median-sagittal plane at six frontal locations (−30, −15, 0, 15, 30, 45), as well as above (90) and behind (180) the listener. The experiments were conducted in a sound-treated room with the speakers concealed from view. Stimuli were 200 ms in duration and presented from only one speaker at a time. On each trial subjects used a pen to mark the perceived stimulus location(s) on a pre-printed coordinate diagram; subjects could indicate the perception of multiple sources and accurately represent auditory image widths and/or ambiguities. Preliminary data confirm historical results showing that localization of single noise bands depends on center frequency and bandwidth. When localizing multiple-band stimuli, responses depended on band density: with a few sparse bands, most subjects heard multiple source locations; for high band densities, subjects heard a single source at or near the true speaker location. [Work supported by NIDCD (R01 00100).]
On the Performance of Bond Functions and Basis Set Extrapolation Techniques in High-Accuracy Calculations of Interatomic Potentials. A Helium Dimer Study
Authors: Jeziorska Małgorzata , Bukowski Robert , Cencek Wojciech , Jaszuński Michał , Jeziorski Bogumił , Szalewicz Krzysztof
Published: March 2003

Helium dimer interaction energies, Eint, obtained recently using the Gaussian geminal implementation of the coupled cluster doubles (CCD) and singles and doubles (CCSD) theory, were employed to evaluate the performance of conventional orbital calculations applying the correlation-consistent polarized valence X-tuple zeta (cc-pVXZ) bases, with X ranging from 4 to 7, and very large sets of bond functions. We found that while the bond functions improve dramatically the convergence of the doubles and triples contribution to the interaction energy, these functions are inefficient or even counterproductive in predicting the effect of the single excitations and the small contribution beyond the CCSD(T) (CCSD model with noniterative account of triple excitations) level of electronic structure theory. We also found that bond functions are very effective in extrapolation techniques. Using simple two-point extrapolations based on the single-power laws X-2 and X-3 for the basis set truncation error, the Gaussian geminal CCSD result for Eint, equal to -9.150 ± 0.001 K at the equilibrium interatomic distance of R = 5.6 bohr, could be reproduced with an error of 2-3 mK. Linear extrapolation of the functional dependence of the CCSD energy on the value of the second-order Møller-Plesset energy and the use of the known accurate value of the latter leads to an even smaller error. Using these extrapolation techniques with basis sets up to doubly augmented septuple-zeta quality and containing large sets of bond functions, we estimated the contribution of triple excitations within the CCSD(T) model to be -1.535 ± 0.002 K, with the error bars reflecting the spread of extrapolated results. The contribution beyond the CCSD(T) model, estimated from full configuration interaction (FCI) calculations with up to 255 orbitals, amounts to -0.323 ± 0.005 K. Combining the Gaussian geminal value of the CCSD energy with the orbital estimations of the CCSD(T) and FCI contributions, we found that Eint = -11.008 ± 0.008 K. This value is consistent with recent high-level orbital computations (van Mourik T., Dunning T. H.: J. Chem. Phys. 1999, 111, 9246; Klopper W.: J. Chem. Phys. 2001, 115, 761) but has substantially tighter error bounds. It differs somewhat, however, from the value of -10.98 ± 0.02 K obtained recently from the "exact" quantum Monte Carlo calculations (Anderson J. B.: J. Chem. Phys. 2001, 115, 4546).
Quantum Resonances: Line Profiles and Dynamics
Authors: Paidarová Ivana , Durand Philippe
Published: March 2003

The wave operator theory of quantum dynamics is reviewed and applied to the study of line profiles and to the determination of the dynamics of interacting resonances. Energy-dependent and energy-independent effective Hamiltonians are investigated. The q-reversal effect in spectroscopy is interpreted in terms of interfering Fano profiles. The dynamics of an hydrogen atom subjected to a strong static electric field is revisited.
GRAVITY ON NONCOMMUTATIVE D-BRANES
Authors: ARDALAN F. , ARFAEI H. , GAROUSI M. R. , GHODSI A.
Published: March 2003

The effective action for the low energy scattering of two gravitons with a D-brane in the presence of a constant antisymmetric B field in bosonic string theory is calculated and the modification to the standard D-brane action to first order in α′ is obtained.
FLUID FLOW AND INERTIAL FORCES IN BLACK HOLE SPACE–TIMES
Authors: MUKHOPADHYAY BANIBRATA , PRASANNA A. R.
Published: March 2003

We discuss the nature of the radial and azimuthal components of centrifugal force associated with fluid flows in the equatorial plane of black hole space–times. The equations of motion are solved for the radial and azimuthal components of the three-velocity Vi which are then used in evaluating the nature of the various components of inertial accelerations. It is shown that the reversal of centrifugal force is governed mainly by the dominance of the azimuthal velocity and the reversal occurs for r, mostly at 2m ≲ r ≲ 3m, depending upon the boundary condition.
ATOMIC RADIATIVE TRANSITIONS IN THERMO FIELD DYNAMICS
Authors: TOMAZELLI J. L. , COSTA L. C.
Published: March 2003

In this work we rederive the Lamb–Retherford energy shift for an atomic electron in the presence of a thermal radiation. Using the Dalibard, Dupont–Roc and Cohen–Tannoudji (DDC) formalism, where physical observables are expressed as convolutions of suitable statistical functions, we construct the electromagnetic field propagator of thermo field dynamics in the Coulomb gauge in order to investigate finite temperature effects on the atomic energy levels. In the same context, we also analyze the problem of the ground state stability.
NONCOMMUTATIVE INSTANTONS ON d = 2n PLANES FROM MATRIX MODELS
Authors: VALTANCOLI P.
Published: March 2003

In the case of an invertible coordinate commutator matrix θij, we derive a general instanton solution of the noncommutative gauge theories on d = 2n planes given in terms of n oscillators.
Φ-MEASURE AND DISORIENTED CHIRAL CONDENSATES
Authors: MOHANTY B.
Published: March 2003

Fluctuations in the ratio of neutral to charged pions arising due to formation of disoriented chiral condensates (DCC) are discussed using the Φ-measure. The properties of the measure for various cases of DCC and non-DCC are discussed. The effect of detector efficiencies and other experimental factors are presented. Application of the Φ-measure to simulated data, within the context of a simple DCC model and to experimental data are also discussed.
INFRARED RENORMALON EFFECTS ON LIGHT MESONS ELECTROMAGNETIC TRANSITION FORM FACTOR FMγ*(Q2, ω)
Authors: MAMEDOVA YEGANA V.
Published: March 2003

The light pseudoscalar π0, η and η′ mesons electromagnetic transition γ* + γ* → M form factors FMγ*(Q2,ω) are calculated, applying the perturbative QCD factorization formula and the frozen coupling constant approximation. In the computations the O(αS) order expression for FMγ*(Q2,ω) and the mesons' infrared renormalon corrected distribution amplitudes are used. In the case of the η and η′ mesons, the SUf(3) ordinary octet-singlet mixing scheme is utilized. Comparisons are made with the results obtained, employing the mesons' ordinary distribution amplitudes and with γ + γ* → M transition form factors.
OPEN STRINGS IN THE SL(2,R) WZWN MODEL WITH SOLUTION FOR A RIGIDLY ROTATING STRING
Authors: LOMHOLT M. A. , LARSEN A. L.
Published: March 2003

Boundary conditions and gluing conditions for open strings and D-branes in the SL (2,R) WZWN model, corresponding to AdS 3, are discussed. Some boundary conditions and gluing conditions previously considered in the literature are shown to be incompatible with the variation principle.

We then consider open string boundary conditions corresponding to a certain field-dependent gluing condition. This allows us to consider open strings with constant energy and angular momentum. Classically, these open strings naturally generalize the open strings in flat Minkowski space. For rigidly rotating open strings, we show that the torsion leads to a bending and an unfolding. We also derive the SL (2,R) Regge relation, which generalizes the linear Minkowski Regge relation. For "high" mass, it takes the form L ≈ ± M/H, where H is the scale of the SL (2,R) group manifold.
Optimization Models of Sound Systems Using Genetic Algorithms
Authors: Ke Jinyun , Ogura Mieko , Wang William S.-Y.
Published: March 2003

In this study, optimization models using genetic algorithms (GAs) are proposed to study the configuration of vowels and tone systems. As in previous explanatory models that have been used to study vowel systems, certain criteria, which are assumed to be the principles governing the structure of sound systems, are used to predict optimal vowels and tone systems. In most of the earlier studies only one criterion has been considered. When two criteria are considered, they are often combined into one scalar function. The GA model proposed for the study of tone systems uses a Pareto ranking method that is highly applicable for dealing with optimization problems having multiple criteria. For optimization of tone systems, perceptual contrast and markedness complexity are considered simultaneously. Although the consistency between the predicted systems and the observed systems is not as significant as those obtained for vowel systems, further investigation along this line is promising.
A Systematic Comparison of Various Statistical Alignment Models
Authors: Och Franz Josef , Ney Hermann
Published: March 2003

We present and compare various methods for computing word alignments using statistical or heuristic models. We consider the five alignment models presented in Brown, Della Pietra, Della Pietra, and Mercer (1993), the hidden Markov alignment model, smoothing techniques, and refinements. These statistical models are compared with two heuristic models based on the Dice coefficient. We present different methods for combining word alignments to perform a symmetrization of directed statistical alignment models. As evaluation criterion, we use the quality of the resulting Viterbi alignment compared to a manually produced reference alignment. We evaluate the models on the German-English Verbmobil task and the French-English Hansards task. We perform a detailed analysis of various design decisions of our statistical alignment system and evaluate these on training corpora of various sizes. An important result is that refined alignment models with a first-order dependence and a fertility model yield significantly better results than simple heuristic models. In the Appendix, we present an efficient training algorithm for the alignment models presented.
Graph-Based Generation of Referring Expressions
Authors: Krahmer Emiel , Erk Sebastiaan van , Verleg André
Published: March 2003

This article describes a new approach to the generation of referring expressions. We propose to formalize a scene (consisting of a set of objects with various properties and relations) as a labeled directed graph and describe content selection (which properties to include in a referring expression) as a subgraph construction problem. Cost functions are used to guide the search process and to give preference to some solutions over others. The current approach has four main advantages: (1) Graph structures have been studied extensively, and by moving to a graph perspective we get direct access to the many theories and algorithms for dealing with graphs; (2) many existing generation algorithms can be reformulated in terms of graphs, and this enhances comparison and integration of the various approaches; (3) the graph perspective allows us to solve a number of problems that have plagued earlier algorithms for the generation of referring expressions; and (4) the combined use of graphs and cost functions paves the way for an integration of rule-based generation techniques with more recent stochastic approaches.
Word Reordering and a Dynamic Programming Beam Search Algorithm for Statistical Machine Translation
Authors: Tillmann Christoph , Ney Hermann
Published: March 2003

In this article, we describe an efficient beam search algorithm for statistical machine translation based on dynamic programming (DP). The search algorithm uses the translation model presented in Brown et al. (1993). Starting from a DP-based solution to the traveling-salesman problem, we present a novel technique to restrict the possible word reorderings between source and target language in order to achieve an efficient search algorithm. Word reordering restrictions especially useful for the translation direction German to English are presented. The restrictions are generalized, and a set of four parameters to control the word reordering is introduced, which then can easily be adopted to new translation directions. The beam search procedure has been successfully tested on the Verbmobil task (German to English, 8,000-word vocabulary) and on the Canadian Hansards task (French to English, 100,000-word vocabulary). For the medium-sized Verbmobil task, a sentence can be translated in a few seconds, only a small number of search errors occur, and there is no performance degradation as measured by the word error criterion used in this article.
The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway
Authors: Spinetti Gaia , Bernardini Giovanni , Camarda Grazia , Mangoni Antonella , Santoni Angela , Capogrossi Maurizio C , Napolitano Monica
Published: March 2003

Several chemokines have been shown to regulate cellular apoptosis following discrete stimuli. It was previously demonstrated that the CC chemokine CCL1 (I-309) rescues thymic lymphoma cells from apoptois by unknown mechanisms. The aim of our study was to characterize the role of the CC chemokine receptor 8 (CCR8), the only described receptor for CCL1, in the rescue of murine thymic lymphoma cells and murine thymocytes from dexamethasone (dex)-induced apoptosis. We show here that the CCR8-restricted agonist Kaposi sarcoma-associated herpesvirus-encoded chemokine viral macrophage-inflammatory protein-1 (vMIP-1) rescues thymic lymphoma cells from dex-induced apoptosis, similar to CCL1, and that such rescue is extracellular-regulated kinase-dependent. Although it has been hypothesized that the rescuing effect of CCL1 from apoptosis could be CCR8-mediated, here, we formally demonstrate the role of such receptor as its selective antagonist encoded by the MC148 gene of molluscum contagiosum virus MC148/vMCC-I inhibits v-MIP-1- and CCL1-induced rescue activity. In addition, CCR8 ligands inhibit dex-induced apoptosis of murine thymocytes with potential implications for thymic selection.
P-selectin mediates IL-13-induced eosinophil transmigration but not eotaxin generation in vivo: a comparative study with IL-4-elicited responses
Authors: Larbi Karen Y , Dangerfield John P , Culley Fiona J , Marshall Diane , Haskard Dorian O , Jose Peter J , Williams Timothy J , Nourshargh Sussan
Published: March 2003

The study investigated the role of P-selectin in the responses of eosinophil transmigration and eotaxin generation in vivo elicited by interleukin (IL)-13, as compared with IL-4. Two murine models of leukocyte transmigration were used, migration into cytokine-stimulated peritoneal cavities and through stimulated cremasteric venules, as observed by intravital microscopy. In mice lacking P-selectin, eosinophil infiltration elicited by the cytokines in the peritonitis model was totally inhibited. In the cremaster muscle, however, although spontaneous leukocyte-rolling flux and stimulated leukocyte firm adhesion were inhibited by ∼97% and ∼48%, respectively, stimulated transmigration was unaffected. However, IL-13-induced leukocyte transmigration was totally blocked in P-selectin-deficient mice treated with an anti-α4 integrin monoclonal antibody (mAb; PS/2). In comparison, treatment of wild-type mice with the anti-α4 integrin mAb resulted in only partial suppression of IL-13-induced leukocyte transmigration. Significant levels of eotaxin were detected in response to IL-13/IL-4 in both tissues in P-selectin-deficient animals. In conclusion, the regulatory role of P-selectin in leukocyte transmigration elicited by IL-13 appears to be tissue-specific, a phenomenon that is independent of the ability of the cytokine to stimulate eotaxin generation.
Peripheral blood-derived bovine dendritic cells promote IgG1-restricted B cell responses in vitro
Authors: Bajer Anna A , Garcia-Tapia David , Jordan Kimberly R , Haas Karen M , Werling Dirk , Howard Chris J , Estes D Mark
Published: March 2003

Regulation of humoral responses involves multiple cell types including the requirements for cognate interactions between T and B cells to drive CD40-dependent responses to T-dependent antigens. A third cell type has also been shown to play an essential role, the dendritic cell (DC). We demonstrate that bovine peripheral blood-derived (PB)-DC are similar in function to features described for human interstitial DC including the production of signature type 2 cytokines [interleukin (IL)-13, IL-10]. PB-DC express moderate-to-high costimulatory molecule expression, and major histocompatibility complex class II is negative for CD14 expression and has low or no expression of CD11c. Consistent with the interstitial phenotype is the ability of PB-DC to influence B cell activation and differentiation via direct expression of CD40L and type 2 cytokines. Collectively, these results suggest that direct B cell-DC interactions may promote an immunoglobulin-isotype expression pattern consistent with type 2 responses, independent of direct T cell involvement.
The role of CCL22 (MDC) for the recruitment of eosinophils during allergic pleurisy in mice
Authors: Pinho Vanessa , Oliveira Sandra H , Souza Danielle G , Vasconcelos Denise , Alessandri Ana Letícia , Lukacs Nicholas W , Teixeira Mauro M
Published: March 2003

Eosinophils are important inflammatory cells in allergic diseases. In the present study, we have investigated the effects of CCL22 on the recruitment of eosinophils in vivo and in vitro. CCL22 induced a dose- and time-dependent recruitment of eosinophils into the pleural cavity of mice, and this was dependent on the release of platelet-activating factor (PAF) and subsequent generation of CCL11. However, in an allergic pleurisy model, an anti-CCL22 polyclonal antibody given during sensitization or before challenge had no significant effect on eosinophil recruitment. CCL22 did not induce eosinophil chemotaxis in vitro but was able to induce eosinophil degranulation in vitro and in vivo. In conclusion, we show that although exogenously added CCL22 may induce eosinophil migration in vivo via release of PAF and CCL11 (eotaxin), endogenous production of CCL22 does not drive eosinophil migration during allergic inflammation. However, CCL22 may be an important activator of eosinophils once these cells have migrated into tissue.
Rational approaches to human cancer immunotherapy
Authors: Davis Ian D , Jefford Michael , Parente Phillip , Cebon Jonathan
Published: March 2003

Over most of the 20th century, immunotherapy for cancer was based on empiricism. Interesting phenomena were observed in the areas of cancer, infectious diseases, or transplantation. Inferences were made and extrapolated into new approaches for the treatment of cancer. If tumors regressed, the treatment approaches could be refined further. However, until the appropriate tools and reagents were available, investigators were unable to understand the biology underlying these observations. In the early 1990s, the first human tumor T cell antigens were defined and dendritic cells were discovered to play a pivotal role in antigen presentation. The current era of cancer immunotherapy is one of translational research based on known biology and rationally designed interventions and has led to a rapid expansion of the field. The beginning of the 21st century brings the possibility of a new era of effective cancer immunotherapy, combining rational, immunological treatments with conventional therapies to improve the outcome for patients with cancer.
Malignant counterpart of myeloid dendritic cell (DC) belonging to acute myelogenous leukemia (AML) exhibits a dichotomous immunoregulatory potential
Authors: Fujii Shin-ichiro , Shimizu Kanako , Koji Fujimoto , Kawano Fumio
Published: March 2003

Dendritic cells (DCs) play a central role in immune regulation. Some leukemic cells are argued to be malignant counterparts of DC because of their ability to differentiate into leukemic DC. We characterize DC-like leukemia homogenously expressing CD11c+CD86+ in acute myelogenous leukemia patients. They express the Wilms’ tumor-1 antigen and common DC phenotypes (i.e., fascin+, CD83+, and DR+) directly. Purified leukemic cells produce interleukin-12 (IL-12) simultaneously with Fas ligand (FasL) and IL-6, which may suppress T cell-mediated immunity. These cells can elicit strong allogeneic T cell responses as well as induce tumor-specific CD8+ cytotoxic T cells, suggesting that they effectively present tumor-associated antigens. In contrast, they drive primary T cells toward apoptosis mediated in a tumor-specific way by a Fas-FasL interaction. Taken together, DC-like leukemia uniquely influences immune surveillance in contadictory ways, some of which may be involved in the mechanism of immune escape.
The unique target specificity of a nonpeptide chemokine receptor antagonist: selective blockade of two Th1 chemokine receptors CCR5 and CXCR3
Authors: Gao Ping , Zhou Xu-Yu , Yashiro-Ohtani Yumi , Yang Yi-Fu , Sugimoto Naotoshi , Ono Shiro , Nakanishi Tsuyoshi , Obika Satoshi , Imanishi Takeshi , Egawa Takeshi , Nagasawa Takashi , Fujiwara Hiromi , Hamaoka Toshiyuki
Published: March 2003

CC chemokine receptor (CCR) 5 and CXC chemokine receptor (CXCR)3 are expressed on T helper cell type 1 cells and have been implicated in their migration to sites of inflammation. Our preceding study demonstrated that a nonpeptide synthetic CCR5 antagonist, TAK-779 {N, N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6, 7-dihydro-5H-benzocyclohepten-8-yl]carbon-yl]amino]benzyl]-tetrahydro-2H-pyran4-aminium chloride, inhibits the development of experimentally induced arthritis by modulating the migration of CCR5+/CXCR3+ T cells to joints. The present study investigated the functional properties of TAK-779, including the effect of this antagonist on CXCR3 function. For this purpose, transfectants expressing mouse CCR5 (mCCR5) or mCXCR3 and expressing mCCR4 or mCXCR4 as controls were established by introducing each relevant gene into 2B4 T cells and were subjected to the following assays. First, the ligand binding to chemokine receptors was assayed by incubating transfectants with [125I]-labeled relevant ligand or with the unlabeled relevant ligand followed by staining with anti-ligand antibody. Second, chemokine-induced lymphocyte function-associated antigen-1 (LFA-1) activation was assayed by measuring the adhesion of cells to microculture plates coated with purified intercellular adhesion molecule-1. Third, chemokine-stimulated chemotaxis was assayed by observing the cell migration through transwells. In these assays, TAK-779 blocked the ligand binding as well as LFA-1 up-regulating and chemotactic function of mCXCR3 and mCCR5 but did not elicit a biologically significant inhibition of those functions of mCCR4 and mCXCR4. These observations indicate the unique target specificity of TAK-779 and explain why this antagonist efficiently blocks the migration of T cells expressing CCR5 and CXCR3 to sites of inflammation.
Fructose-1,6-biphosphate and nucleoside pool modifications prevent neutrophil accumulation in the reperfused intestine
Authors: Sola Anna , Panés Julián , Xaus Carme , Hotter Georgina
Published: March 2003

Fructose-1,6-biphosphate (F16BP) attenuates ischemia/reperfusion (I/R) injury by inhibiting microvascular leukocyte adhesion or reducing neutrophil-derived oxygen free-radical production, but the causes of this action, the mechanisms in vivo, and the possible implication of nucleoside pool modifications are still controversial issues. We explored whether F16BP’s inhibition of free-radical production and neutrophil recruitment is a result of its effect on adenosine (Ado) accumulation during intestinal I/R injury. The effects of F16BP administration were tested on the nucleotide/nucleoside metabolism at the end of the ischemic period and on microvascular neutrophil recruitment and free-radical production after reperfusion in vivo, in the presence or absence of Ado deaminase (ADA). Infusion of F16BP markedly increaed endogenous Ado, decreased xanthine accumulation during the ischemic period, and inhibited neutrophil recruitment and subsequent neutrophil free-radical generation during reperfusion. Administration of ADA reversed these processes. The results provide strong evidence that F16BP prevents neutrophil accumulation and neutrophil free-radical generation during intestinal I/R by a key mechanism that modifies the nucleoside pool, leading to an endogenous accumulation of Ado and to a reduction of xanthine during ischemia.
Interleukin-18
Authors: Gracie J Alastair , Robertson Susan E , McInnes Iain B
Published: March 2003

Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases. This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection. IL-18, previously known as interferon-γ (IFN-γ)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN-γ production by murine splenocytes [1]. IL-18 was cloned from a murine liver cell cDNA library generated from animals primed with heat-killed Propionibacterium acnes and subsequently challenged with lipopolysaccharide [2]. Nucleotide sequencing of murine IL-18 predicted a precursor polypeptide of 192 amino acids lacking a conventional signal peptide and a mature protein of 157 amino acids. Subsequent cloning of human IL-18 cDNA revealed 65% homology with murine IL-18 [3] and showed that both contain n unusual leader sequence consisting of 35 amino acids at their N terminus.
Possible contribution of apoptosis-inducing factor (AIF) and reactive oxygen species (ROS) to UVB-induced caspase-independent cell death in the T cell line Jurkat
Authors: Murahashi Hideaki , Azuma Hiroshi , Zamzami Naoufal , Furuya Ko-ji , Ikebuchi Kenji , Yamaguchi Miki , Yamada Yoshiko , Sato Norihiro , Fujihara Mitsuhiro , Kroemer Guido , Ikeda Hisami
Published: March 2003

We analyzed the mechanism of UVB-induced cell death using the Jurkat T cell line. Apoptosis was assessed by measuring phosphatidylserine (PS) externalization, caspase activity, the decrease in mitochondrial membrane potential (ΔΨm), nucleosomal DNA fragmentation, and morphological changes such as chromatin condensation. The mitochondrio-nuclear translocation of apoptosis-inducing factor (AIF) was evaluated by confocal laser microscopy. The cell death pattern of UVB-irradiated cells was similar to the Fas-induced cell death pattern. However, zVAD-fmk inhibited the nucleosomal fragmentation of DNA but not the externalization of PS, decrease in ΔΨm, or mitochondrio-nuclear translocation of AIF. N-acetyl L-cysteine significantly inhibited the translocation of AIF induced by UVB. These results suggested that caspase-dependent and -independent pathways were involved in UVB-induced cell death in Jurkat cells, and the mitochondrio-nuclear translocation of AIF was associated with the latter pathway. In addition, reactive oxygen species generated by UVB might be involved in inducing the mitochondrio-nuclear translocation of AIF.
Accessibility control and machinery of immunoglobulin class switch recombination
Authors: Zhang Ke
Published: March 2003

Immunoglobulin (Ig) class switching is a process by which B lymphocytes shift from production of IgM to other Ig classes and subclasses via Ig class switch recombination (CSR). Multiple cellular and molecular processes are involved in CSR. Induction of a given IgH germline transcription initiates CSR processes. Ig germline transcription is selectively activated and induced by specific cytokine(s) via cytokine-specific signal pathways, synergized by CD40 signaling, and optimized by the 3′ Igα enhancers through locus control region function. Following Ig germline transcription, the switch-region DNA undergoes conformational changes so that it can serve as an appropriate substrate for nicking and cleavage by switch recombination machinery. Finally, the double-strand breaks in donor and acceptor switch DNAs are processed, repaired, and ligated through a general nonhomologous end join pathway. CSR generates a new transcriptional unit for production of a class-switched Ig isotype.
M-CSF induced differentiation of myeloid precursor cells involves activation of PKC-δ and expression of Pkare
Authors: Junttila Ilkka , Bourette Roland P , Rohrschneider Larry R , Silvennoinen Olli
Published: March 2003

Macrophage-colony stimulating factor (M-CSF) regulates proliferation and differentiation of cells belonging to the monocytic lineage. We investigated the mechanisms of M-CSF differentiation signaling in follicular dendritic cell-P1 cells and analyzed the catalytic activation of different protein kinase C (PKC) isoforms. M-CSF induced rapid catalytic activation of PKC-δ and membrane transocation of the tyrosine phosphorylated form of PKC-δ. Mutation of tyrosine 807 in the M-CSF receptor (Fms) abrogates cell differentiation but not a proliferative response to M-CSF, and FmsY807F failed to activate PKC-δ. We also investigated the downstream signaling pathways from PKC-δ. A cyclic adenosine monophosphate-regulated Ser/Thr kinase gene, protein kinase X (PRKX), has been associated with macrophage differentiation in human cells. We found that M-CSF and PKC-δ induced the expression of the PRKX murine homologue: PKA-related gene. Taken together, our results indicate that PKC-δ functions as a critical mediator of M-CSF-induced differentiation signaling.
Telomere shortening in leukocyte subpopulations from baboons
Authors: Baerlocher Gabriela M , Mak Jennifer , Röth Alexander , Rice Karen S , Lansdorp Peter M
Published: March 2003

To address questions about telomere length regulation in nonhuman primates, we studied the telomere length in subpopulations of leukocytes from the peripheral blood of baboons aged 0.2–26.5 years. Telomere length in granulocytes, B cells, and subpopulations of T cells all decreased with age. Overall, telomere length kinetics were lineage- and cell subset-specific. T cells showed the most pronounced, overall decline in elomere length. Levels of telomerase in stimulated T cells from old animals were lower than in corresponding cells from young animals. Memory T cells with very short telomeres accumulated in old animals. In contrast, the average telomere length values in B cells remained relatively constant from middle age onward. Individual B cells showed highly variable telomere length, and B cells with very long telomeres were observed after the ages of 1–2 years. In general, cell type-specific telomere kinetics in baboons were remarkably similar to those observed in humans.
Short cytoplasmic SDYMNM segment of CD28 is sufficient to convert CTLA-4 to a positive signaling receptor
Authors: Yin Li , Schneider Helga , Rudd Christopher E
Published: March 2003

CD28 and cytotoxic T-lymphocyte antigen (CTLA)-4 are key coreceptors on the surface of T cells that have opposing effects on T cell activation. Although CD28 enhances proliferation, CTLA-4 markedly inhibits the activation process. These opposing roles are particularly surprising given the structural similarity of the cytoplasmic residues of the two receptors. These include the related CD28SDYMNM and CTLA-4GVYVKM motifs. In this study, we have directly addressed whether these related motifs may play different roles in the activation process by swapping the CTLA-4GVYVKM motif with the CD28SDYMNM motif. Remarkably, stable transfectants of the T cell hybridoma DC27.10 showed that substitution of CTLA-4GVYVKM was sufficient to convert CTLA-4 from a negative signaling coreceptor to a positive CD28-like coreceptr. CD28SDYMNM is therefore sufficient to convey positive signals within CTLA-4. These results demonstrate that CD28SDYMNM and CTLA-4GVYVKM motifs contain sufficient information to distinguish positive versus negative coreceptor signaling in T cells.
Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the production of inflammatory mediators by activated microglia
Authors: Delgado Mario , Leceta Javier , Ganea Doina
Published: March 2003

Microglia play a central role in the regulation of immune and inflammatory activities, as well as tissue remodeling in the central nervous system. However, activation of microglia is a histopathological hallmark of several neurodegenerative diseases. Pathological microglial activation is believed to contribute to progressive damage in neurodegenerative diseases through the release of proinflammatory and/or cytotoxic factors, including tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-12, and nitric oxide (NO). Hence, it is important to unravel mechanisms regulating microglia activation of inflamed brain parenchyma to provide insights into efficient therapeutic intervention. This study examines the role of two anti-inflammatory neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP) on the production of various proinflammatory factors by endotoxin-stimulated miroglia. VIP and PACAP inhibit TNF-α, IL-1β, IL-6, and NO production by lipopolysaccharide (LPS)-activated microglia. The specific type 1 VIP receptor mediates the inhibitory effect of VIP/PACAP, and cyclic adenosine monophosphate is the major, second messenger involved. VIP and PACAP regulate the production of these proinflammatory factors at a transcriptional level by inhibiting p65 nuclear translocation and nuclear factor-κB-DNA binding. This effect is mediated, as neuropeptides stabilize the inhibitor IκB by inhibiting LPS-induced IκB-kinase activity. Therefore, the inhibitory effects on the production of proinflammatory mediators define VIP and PACAP as “microglia-deactivating factors” with significant, therapeutical potential for inflammatory/degenerative brain disorders.
Adherence influences monocyte responsiveness to interleukin-10
Authors: Petit-Bertron Anne-France , Fitting Catherine , Cavaillon Jean-Marc , Adib-Conquy Minou
Published: March 2003

We studied the effects of adherence on the properties of interleukin (IL)-10 on monocyte-enriched peripheral blood mononuclear cells. We found that the decrease of CD11b expression induced by IL-10 was enhanced by adherence. Toll-like receptor (TLR)2 and TLR4 mRNA, as well as TLR4 surface expression, were significantly up-regulated by IL-10 in adherent cells. The absence of adherence prevented the inhibitory effects of IL-10 on lipopolysaccharide-induced tumor necrosis factor (TNF) and granulocyte-colony stimulating factor production and increased IL-1β production and soluble TNF receptor II release in IL-10-pretreated cells. Similarly, the absence of adherence amplified the enhancement of phagocytosis induced by IL-10. Tyk2 and signal transducer and activator of transcription 3 (STAT3) phosphorylation and suppressr of cytokine signaling 3 (SOCS3) expression were induced by IL-10 in both conditions, but a longer activation and/or expression were observed in adherent monocytes. Finally, heme oxygenase-1, an anti-inflammatory molecule, was induced by IL-10 in adherent monocytes, whereas its expression remained low in nonadherent cells. Altogether, these data illustrate that adherence modulates the properties and the anti-inflammatory effects of IL-10.