bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Qa-1bPeptide Binding Specificity and the Capacity of Cd94/Nkg2a to Discriminate between Qa-1–Peptide Complexes
Authors: Kraft Jennifer R. , Vance Russell E. , Pohl Jan , Martin Amy M. , Raulet David H. , Jensen Peter E.
Published: July 2002

The major histocompatibility complex class Ib protein, Qa-1b, serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1b peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1b. A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1b can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1b. Flow cytometry experiments with Qa-1b tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1b complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells.
Development of a Peptide Inhibitor of Hyaluronan-Mediated Leukocyte Trafficking
Authors: Mummert Mark E. , Mohamadzadeh Mansour , Mummert Diana I. , Mizumoto Norikatsu , Takashima Akira
Published: July 2002

Hyaluronan (HA), a high molecular weight glycosaminoglycan, is expressed abundantly in the extracellular matrix and on cell surfaces. Although HA is known to bind many adhesion molecules, little information has been available with respect to its direct physiological role. In this study, we developed a novel 12-mer (GAHWQFNALTVR) peptide inhibitor of HA, termed “Pep-1,” by using phage display technology. Pep-1 showed specific binding to soluble, immobilized, and cell-associated forms of HA, and it inhibited leukocyte adhesion to HA substrates almost completely. Systemic, local, or topical administration of Pep-1 inhibited the expression of contact hypersensitivity responses in mice by blocking skin-directed homing of inflammatory leukocytes. Pep-1 also inhibited the sensitization phase by blocking hapten-triggered migration of Langerhans cells from the epidermis. These observations document that HA plays an essential role in “two-way” trafficking of leukocytes to and from an inflamed tissue, and thus provide technical and conceptual bases for testing the potential efficacy of HA inhibitors (e.g., Pep-1) for inflammatory disorders.
Nitric Oxide–Dependent Activation of P53 Suppresses Bleomycin-Induced Apoptosis in the Lung
Authors: Davis Darren W. , Weidner Douglas A. , Holian Andrij , McConkey David J.
Published: July 2002

Chronic inflammation leading to pulmonary fibrosis develops in response to environmental pollutants, radiotherapy, or certain cancer chemotherapeutic agents. We speculated that lung injury might be mediated by p53, a proapoptotic transcription factor widely implicated in the response of cells to DNA damage. Intratracheal administration of bleomycin led to caspase-mediated DNA fragmentation characteristic of apoptosis. The effects of bleomycin were associated with translocation of p53 from the cytosol to the nucleus only in alveolar macrophages that had been exposed to the drug in vivo, suggesting that the lung microenvironment regulated p53 activation. Experiments with a thiol antioxidant (N-acetylcysteine) in vivo and nitric oxide (NO) donors in vitro confirmed that reactive oxygen species were required for p53 activation. A specific role for NO was demonstrated in experiments with inducible nitric oxide synthase (iNOS)−/− macrophages, which failed to demonstrate nuclear p53 localization after in vivo bleomycin exposure. Strikingly, rates of bleomycin-induced apoptosis were at least twofold higher in p53−/− C57BL/6 mice compared with heterozygous or wild-type littermates. Similarly, levels of apoptosis were also twofold higher in the lungs of iNOS−/− mice than were observed in wild-type controls. Consistent with a role for apoptosis in chronic lung injury, levels of bleomycin-induced inflammation were substantially higher in iNOS−/− and p53−/− mice compared with wild-type controls. Together, our results demonstrate that iNOS and p53 mediate a novel apoptosis-suppressing pathway in the lung.
Selective Inhibition of Vascular Endothelial Growth Factor–Mediated Angiogenesis by Cyclosporin a
Authors: Hernández Gabriela L. , Volpert Olga V. , Íñiguez Miguel A. , Lorenzo Elisa , Martínez-Martínez Sara , Grau Raquel , Fresno Manuel , Redondo Juan Miguel
Published: July 2002

Cyclosporin A (CsA) is an immunosuppressive drug that inhibits the activity of transcription factors of the nuclear factor of activated T cells (NFAT) family, interfering with the induction of cytokines and other inducible genes required for the immune response. Here we show that CsA inhibits migration of primary endothelial cells and angiogenesis induced by vascular endothelial growth factor (VEGF); this effect appears to be mediated through the inhibition of cyclooxygenase (Cox)-2, the transcription of which is activated by VEGF in primary endothelial cells. Consistent with this, we show that the induction of Cox-2 gene expression by VEGF requires NFAT activation. Most important, the CsA-mediated inhibition of angiogenesis both in vitro and in vivo was comparable to the Cox-2 inhibitor NS-398, and reversed by prostaglandin E2. Furthermore, the in vivo corneal angiogenesis induced by VEGF, but not by basic fibroblast growth factor, was selectively inhibited in mice treated with CsA systemically. These findings involve NFAT in the regulation of Cox-2 in endothelial cells, point to a role for this transcription factor in angiogenesis, and may provide a novel mechanism underlying the beneficial effects of CsA in angiogenesis-related diseases such as rheumatoid arthritis and psoriasis.
Selective Abrogation of Major Histocompatibility Complex Class II Expression on Extrahematopoietic Cells in Mice Lacking Promoter IV of the Class II Transactivator Gene
Authors: Waldburger Jean-Marc , Suter Tobias , Fontana Adriano , Acha-Orbea Hans , Reith Walter
Published: July 2002

MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice exhibit selective abrogation of interferon (IFN)-γ–induced MHCII expression on a wide variety of non-bone marrow–derived cells, including endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression on cortical thymic epithelial cells, and thus positive selection of CD4+ T cells, is also abolished. In contrast, constitutive and inducible MHCII expression is unaffected on professional antigen-presenting cells, including B cells, dendritic cells, and IFN-γ–activated cells of the macrophage lineage. pIV−/− mice have thus allowed precise definition of CIITA pIV usage in vivo. Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease.
Migratory Properties of Naive, Effector, and Memory Cd8+ T Cells
Authors: Weninger Wolfgang , Crowley Maura A. , Manjunath N. , von Andrian Ulrich H.
Published: July 2002

It has been proposed that two different antigen-experienced T cell subsets may be distinguishable by their preferential ability to home to lymphoid organs (central memory cells) or nonlymphoid tissues (effector memory/effector cells). We have shown recently that murine antigen-primed CD8+ T cells cultured in interleukin (IL)-15 (CD8IL-15) resemble central memory cells in phenotype and function. In contrast, primed CD8+ T cells cultured in IL-2 (CD8IL-2) become cytotoxic effector cells. Here, the migratory behavior of these two subsets was investigated. Naive, CD8IL-15 cells and, to a lesser degree, CD8IL-2 cells localized to T cell areas in the spleen, but only naive and CD8IL-15 cells homed to lymph nodes (LNs) and Peyer's patches. Intravital microscopy of peripheral LNs revealed that CD8IL-15 cells, but not CD8IL-2 cells, rolled and arrested in high endothelial venules (HEVs). Migration of CD8IL-15 cells to LNs depended on L-selectin and required chemokines that bind CC chemokine receptor (CCR)7. Both antigen-experienced populations, but not naive T cells, responded to inflammatory chemokines and accumulated at sites of inflammation. However, CD8IL-2 cells were 12 times more efficient in migrating to inflamed peritoneum than CD8IL-15 cells. Furthermore, CD8IL-15 cells proliferated rapidly upon reencounter with antigen at sites of inflammation. Thus, central memory-like CD8IL-15 cells home avidly to lymphoid organs and moderately to sites of inflammation, where they mediate rapid recall responses, whereas CD8IL-2 effector T cells accumulate in inflamed tissues, but are excluded from most lymphoid organs.
Antitumor Monoclonal Antibodies Enhance Cross-Presentation of Cellular Antigens and the Generation of Myeloma-specific Killer T Cells by Dendritic Cells
Authors: Dhodapkar Kavita M. , Krasovsky Joseph , Williamson Barbara , Dhodapkar Madhav V.
Published: July 2002

The mechanism of antitumor effect of monoclonal antibodies (mAbs) is not fully understood. Here we show that coating myeloma cells with anti–syndecan-1 antibody promotes cross-presentation of cellular antigens by dendritic cells (DCs) to autologous T cells from healthy donors. The tumor cells treated with anti–syndecan-1 or isotype-matched control antibody were fed to HLA-mismatched monocyte-derived immature DCs. Tumor cell–loaded mature DCs induced a strong CD8+ T cell response that was specific for the cancer-testis (C-T) antigens expressed in the tumor. The CD8+ T cells killed peptide-pulsed targets, as well as myeloma tumor cells. Importantly, mAbs-coated tumor-loaded DCs were consistently superior to DCs loaded with peptides or dying cells for eliciting tumor-specific killer T cells. This enhanced cross-presentation was not due to enhanced tumor cell uptake or to DC maturation. When mixtures of NY-Eso-1-positive and -negative myeloma cells were captured by DCs, the anti–syndecan-1 antibody had to be on the NY-Eso-1-positive cells to elicit NY-Eso-1–specific response. Cross-presentation was inhibited by pretreatment of DCs with Fcγ receptor blocking antibodies. Targeting of mAb-coated tumors to DCs may contribute to the efficacy of tumor-reactive mAb and offers a new strategy for immunotherapy.
Presentation of the Same Glycolipid by Different CD1 Molecules
Authors: Shamshiev A. , Gober H.-J. , Donda A. , Mazorra Z. , Mori L. , De Libero G.
Published: July 2002

Five CD1 molecules are expressed in humans and it is unclear whether they have specialized or redundant functions. We found that sulfatide is a promiscuous CD1-binding ligand and have isolated T cell clones that are specific for sulfatide and restricted by distinct CD1 molecules. These clones have been used to compare the capacity of different CD1 to present the same glycolipid, to induce effector functions, and to form persistent immunogenic complexes. CD1a, CD1b, and CD1c molecules similarly load sulfatide on the cell surface without processing, and prime Th1 and Th2 responses. Stimulation by sulfatide-loaded CD1a persists much longer than that by CD1b and CD1c in living cells. Use of recombinant soluble CD1a confirmed the prolonged capacity to stimulate T cells. Moreover, other glycosphingolipids bind to all CD1, which suggests the presence of additional promiscuous ligands. Thus, group I CD1 molecules present an overlapping set of self-glycolipids, even though they are quite divergent from an evolutionary point of view.
Idiotypes Expressed Early in Experimental Schistosoma mansoni Infections Predict Clinical Outcomes of Chronic Disease
Authors: Montesano M. Angela , Colley Daniel G. , Willard Margaret T. , Freeman George L. , Secor W. Evan
Published: July 2002

In murine Schistosoma mansoni infections, schistosome-specific cross-reactive idiotypes (CRI) are present in the sera of mice with moderate splenomegaly syndrome (MSS) at 20 wk after infection. In contrast, sera from animals that have the more severe hypersplenomegaly syndrome (HSS) at 20 wk of infection do not express these CRI in their sera. To examine when these regulatory CRI first appear in mice that eventually develop MSS, sera from infected animals were monitored for CRI from 1.5 to 20 wk of infection. In mice that eventually developed MSS, CRI were detected by 5 to 6 wk after infection, plateaued by 8 to 10 wk, and persisted through 20 wk of infection. Animals that developed HSS pathology or that died before 20 wk of infection never expressed CRI. Moreover, CRI levels present in the sera of mice at 6 wk of infection were inversely correlated with splenomegaly and hepatic fibrosis, but not with parasitologic measures, at 20 wk after infection. These results suggest that critical events occur very early in some schistosome infections that induce the production of regulatory idiotypes and that the presence or absence of these idiotypes predicts, and possibly determines, subsequent morbidity.
NadA, a Novel Vaccine Candidate of Neisseria meningitidis
Authors: Comanducci Maurizio , Bambini Stefania , Brunelli Brunella , Adu-Bobie Jeannette , Aricò Beatrice , Capecchi Barbara , Giuliani Marzia Monica , Masignani Vega , Santini Laura , Savino Silvana , Granoff Dan M. , Caugant Dominique A. , Pizza Mariagrazia , Rappuoli Rino , Mora Marirosa
Published: July 2002

Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, is still a major cause of mortality due to sepsis and meningitis. Here we describe NadA, a novel surface antigen of N. meningitidis that is present in 52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37, ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N. gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The guanine/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three well-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), forms high molecular weight oligomers, and binds to epithelial cells in vitro supporting the hypothesis that NadA is important for host cell interaction. NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages.
Increased Expression of the Cardiac L-type Calcium Channel in Estrogen Receptor–deficient Mice
Authors: Johnson Barry D. , Zheng Wei , Korach Kenneth S. , Scheuer Todd , Catterall William A. , Rubanyi Gabor M.
Published: July 2002

Steroid hormones control the expression of many cellular regulators, and a role for estrogen in cardiovascular function and disease has been well documented. To address whether the activity of the L-type Ca2+ channel, a critical element in cardiac excitability and contractility, is altered by estrogen and its nuclear receptor, we examined cardiac myocytes from male mice in which the estrogen receptor gene had been disrupted (ERKO mice). Binding of dihydropyridine Ca2+ channel antagonist isradipine (PN200-110) was increased 45.6% in cardiac membranes from the ERKO mice compared to controls, suggesting that a lack of estrogen receptors in the heart increased the number of Ca2+ channels. Whole-cell patch clamp of acutely dissociated adult cardiac ventricular myocytes indicated that Ca2+ channel current was increased by 49% and action potential duration was increased by 75%. Examination of electrocardiogram parameters in ERKO mice showed a 70% increase in the QT interval without significant changes in PQ or QRS intervals. These results show that the membrane density of the cardiac L-type Ca2+ channel is regulated by the estrogen receptor and suggest that decreased estrogen may lead to an increase in the number of cardiac L-type Ca2+ channels, abnormalities in cardiac excitability, and increased risk of arrhythmia and cardiovascular disease.
Voltage-dependent Membrane Displacements Measured by Atomic Force Microscopy
Authors: Mosbacher J. , Langer M. , Hörber J.K.H. , Sachs F.
Published: July 2002

Cells use polar molecules in the membrane to sense changes in the transmembrane potential. The opening of voltage-gated ion channels and membrane bending due to the inverse flexoelectric effect are two examples of such electromechanical coupling. We have looked for membrane motions in an electric field using atomic (or scanning) force microscopy (AFM) with the intent of studying voltage-dependent conformational changes of ion channels. Voltage-clamped HEK293 cells were either untransfected controls or transfected with Shaker K+ channels. Using a ± 10-mV peak–peak AC carrier stimulus, untransfected cells moved 0.5–15 nm normal to the plane of the membrane. These movements tracked the voltage at frequencies >1 kHz with a phase lead of 60–120°, as expected of a displacement current. The movement was outward with depolarization, but the holding potential only weakly influenced the amplitude of the movement. In contrast, cells transfected with a noninactivating mutant of Shaker K+channels showed similar movements, but these were sensitive to the holding potential; decreasing with depolarization between −80 and 0 mV. Searching for artifactual origins of these movements, we used open or sealed pipettes and AFM cantilever placements just above the cells. These results were negative, suggesting that the observed movements were produced by the cell membrane rather than by movement of the patch pipette, or by acoustic or electrical interactions of the membrane with the AFM tip. In control cells, the electrical motor may arise from the flexoelectric effect, where changes in potential induce changes in curvature. In transfected cells, it appears that channel-specific movements also occurred. These experiments demonstrate that the AFM may be able to exploit voltage-dependent movements as a source of contrast for imaging membrane components. The electrically induced motility will cause twitching during action potentials, and may have physiological consequences.
A Ricci-semi-symmetric hypersurface of Euclidean space which is not semi-symmetric
Authors: Abdalla Bahaa , Dillen Franki
Published: July 2002

We construct the first explicit example of a Ricci-semi-symmetric hypersurface of Euclidean space which is not semi-symmetric.
Holomorphic helices in a complex space form
Authors: Maeda Sadahiro , Adachi Toshiaki
Published: July 2002

In a complex space form

M
M

we shall investigate a smooth curve

γ
\gamma

which is generated by a holomorphic Killing vector field

X
X

on

M
M

.
Common operator properties of the linear operators 𝑅𝑆 and 𝑆𝑅
Authors: Barnes Bruce
Published: July 2002

Let

S
S

and

R
R

be bounded linear operators defined on Banach spaces,

S
:
X
→
Y

S\colon X\to Y

,

R
:
Y
→
X

R\colon Y\to X

. When

λ
≠
0

\lambda \neq 0

, then the operators

λ
−
S
R

\lambda -SR

and

λ
−
R
S

\lambda -RS

have many basic operator properties in common. This situation is studied in this paper.
Special values of multiple polylogarithms
Authors: Borwein Jonathan , Bradley David , Broadhurst David , Lisoněk Petr
Published: July 2002

Historically, the polylogarithm has attracted specialists and non-specialists alike with its lovely evaluations. Much the same can be said for Euler sums (or multiple harmonic sums), which, within the past decade, have arisen in combinatorics, knot theory and high-energy physics. More recently, we have been forced to consider multidimensional extensions encompassing the classical polylogarithm, Euler sums, and the Riemann zeta function. Here, we provide a general framework within which previously isolated results can now be properly understood. Applying the theory developed herein, we prove several previously conjectured evaluations, including an intriguing conjecture of Don Zagier.
Enriched 𝑃-Partitions
Authors: Stembridge John
Published: July 2002

An (ordinary)PP-partition is an order-preserving map from a partially ordered set to a chain, with special rules specifying where equal values may occur. Examples include number-theoretic partitions (ordered and unordered, strict or unrestricted), plane partitions, and the semistandard tableaux associated with Schur’sSS-functions. In this paper, we introduce and develop a theory of enrichedPP-partitions; like ordinaryPP-partitions, these are order-preserving maps from posets to chains, but with different rules governing the occurrence of equal values. The principal examples of enrichedPP-partitions given here are the tableaux associated with Schur’sQQ-functions. In a sequel to this paper, further applications related to commutation monoids and reduced words in Coxeter groups will be presented.
Hardy inequalities in Orlicz spaces
Authors: Cianchi Andrea
Published: July 2002

We establish a sharp extension, in the framework of Orlicz spaces, of the (

n
n

-dimensional) Hardy inequality, involving functions defined on a domain

G
G

, their gradients and the distance function from the boundary of

G
G

.
On a problem of Byrnes concerning polynomials with restricted coefficients
Authors: Boyd David
Published: July 2002

We consider a question of Byrnes concerning the minimal degree

n
n

of a polynomial with all coefficients in

{
−
1
,
1
}

\{-1,1\}

which has a zero of a given order

m
m

at

x
=
1

x = 1

. For

m
≤
5

m \le 5

, we prove his conjecture that the monic polynomial of this type of minimal degree is given by

∏

k
=
0

m
−
1

(

x

2

k

−
1
)

\prod _{k=0}^{m-1} (x^{2^{k}}-1)

, but we disprove this for

m
≥
6

m \ge 6

. We prove that a polynomial of this type must have

n
≥

e

m

(
1
+
o
(
1
)
)

n \ge e^{\sqrt {m}(1 + o(1))}

, which is in sharp contrast with the situation when one allows coefficients in

{
−
1
,
0
,
1
}

\{-1,0,1\}

. The proofs use simple number theoretic ideas and depend ultimately on the fact that

−
1
≡
1

(
mod

2
)

-1 \equiv 1 \pmod 2

.
The arithmetic and geometry of Salem numbers
Authors: Ghate Eknath , Hironaka Eriko
Published: July 2002

A Salem number is a real algebraic integer, greater than

1
1

, with the property that all of its conjugates lie on or within the unit circle, and at least one conjugate lies on the unit circle. In this paper we survey some of the recent appearances of Salem numbers in parts of geometry and arithmetic, and discuss the possible implications for the ‘minimization problem’. This is an old question in number theory which asks whether the set of Salem numbers is bounded away from

1
1

.
An extensive list of genes that produce alternative transcripts in the mouse.
Authors: Mangan M E , Frazer K S
Published: July 2002

SUMMARY: A single gene can generate multiple transcribed gene products. An extensive list of alternatively transcribed mouse genes has been generated, and is publicly available from http://www.informatics.jax.org/report.html. CONTACT: mgi-help@informatics.jax.org
Ballast: Blast post-processing based on locally conserved
segments
Authors: Plewniak F. , Thompson J. D. , Poch O.
Published: July 2002

Motivation: Blast programs are very efficient in finding relatively strong similarities but some very distantly related sequences are given a very high Expect value and are ranked very low in Blast results. We have developed Ballast, a program to predict local maximum segments (LMSs—i.e. sequence segments conserved relatively to their flanking regions) from a single Blast database search and to highlight these divergent homologues. The TBlastN database searches can also be processed with the help of information from a joint BlastP search.

Results: We have applied the Ballast algorithm to BlastP searches performed with sequences belonging to well described dispersed families (aminoacyl-tRNA synthetases; helicases) against the SwissProt 38 database. We show that Ballast is able to build an appropriate conservation profile and that LMSs are predicted that are consistent with the signatures and motifs described in the literature. Furthermore, by comparing the Blast, PsiBlast and Ballast results obtained on a well defined database of structurally related sequences, we show that the LMSs provide a scoring scheme that can concentrate on top ranking distant homologues better than Blast. Using the graphical user interface available on the Web, specific LMSs may be selected to detect divergent homologues sharing the corresponding properties with the query sequence without requiring any additional database search.

Availability: Web service is at http://igbmc.u-strasbg.fr:8080/ballast.htmland source code is available at ftp://ftp-igbmc.u-strasbg.fr/Ballast/

Contact: plewniak@igbmc.u-strasbg.fr

To whom correspondence should be addressed.
TREE-PUZZLE: maximum likelihood phylogenetic analysis using
quartets and parallel computing
Authors: Schmidt Heiko A. , Strimmer Korbinian , Vingron Martin , von Haeseler Arndt
Published: July 2002

Summary: TREE-PUZZLE is a program package for quartet-based maximum-likelihood phylogenetic analysis (formerly PUZZLE, Strimmer and von Haeseler, Mol. Biol. Evol. , 13, 964–969, 1996) that provides methods for reconstruction, comparison, and testing of trees and models on DNA as well as protein sequences. To reduce waiting time for larger datasets the tree reconstruction part of the software has been parallelized using message passing that runs on clusters of workstations as well as parallel computers.

Availability: http://www.tree-puzzle.de. The program is written in ANSI C. TREE-PUZZLE can be run on UNIX, Windows and Mac systems, including Mac OS X. To run the parallel version of PUZZLE, a Message Passing Interface (MPI) library has to be installed on the system. Free MPI implementations are available on the Web (cf. http://www.lam-mpi.org/mpi/implementations/).

Contact: hschmidt@molgen.mpg.de; haeseler@eva.mpg.de

* To whom correspondence should be addressed.
THE EAST END, THE WEST END, AND KING'S CROSS: ON CLUSTERING IN THE FOUR‐PLAYER HOTELLING GAME
Authors: Huck Steffen , Müller Wieland , Vriend Nicolaas J.
Published: July 2002

We study experimentally a standard four‐player Hotelling location game with a uniform density of consumers and inelastic demand. The pure strategy Nash equilibrium configuration consists of two firms located at one quarter of the “linear city,” and the other two at three quarters. We do not observe convergence to such an equilibrium. In our experimental data we find three clusters. Besides the direct proximity of the two equilibrium locations, this concerns the focal midpoint. Moreover, we observe that whereas this midpoint appears to become more notable over time, other focal points fade away. We explain how these observations are related to best‐response dynamics, and to the fact that the players rely on best‐responses in particular when they are close to the equilibrium configuration.
True Womanhood in Hollywood: Gendered Business Strategies and the Rise and Fall of the Woman Filmmaker, 1896–1928
Authors: Mahar Karen Ward
Published: July 2002

Women flourished as producers, directors, screenwriters, and editors in the first quarter-century of the film industry. But by 1925 their presence in all but screenwriting was severely diminished. The argument of this essay is that the process of gendering the industry ultimately closed studio doors to female filmmakers. As studios moved from the artistic and entrepreneurial stage, conducive to the perceived qualities of women, to the corporate stage, the needs of the industry became masculinized and women were excluded. This process is explored by examining the assumptions regarding gender inherited by the early movie industry and the context in which gender was discussed within the industry, and by asking whether explicit assumptions about the fitness of women and men were ever factors in determining what and who a filmmaker should be.
From genes to individuals: developmental genes and the generation of the phenotype
Authors: Tautz Diethard , Schmid Karl J.
Published: July 2002

The success of the genetic approach to developmental biology has provided us with a suite of genes that are involved in the regulation of ontogenetic pathways. It is therefore time to ask whether and how such genes may be involved in the generation of adaptive phenotypes. Unfortunately, the current results do not provide a clear answer. Most of the genes that have been studied by developmental biologists affect early embryonic traits with major effects on the whole organism. These genes are often highly conserved which allows us to do comparative studies even across phyla. However, whether the same genes are also involved in short–term ecological adaptations remains unclear. The suggestion that early acting ontogenetic genes may also affect late phenotypes comes from the genetic analysis of quantitative traits like bristle numbers inDrosophila. A rough mapping of the major loci affecting these traits shows that these loci might correspond to well known early acting genes. On the other hand, there are also many minor effect loci that are as yet uncharacterized. We suggest that these minor loci might correspond to a different class of genes. In comparative studies of randomly drawn cDNAs fromDrosophilawe find that there is a large group of genes that evolve fast and that are significantly under–represented in normal genetic screens. We speculate that these genes might provide a large, as yet poorly understood, reservoir of genes that might be involved in the evolution of quantitative traits and short–term adaptations.
Dosimetry characterization of catheter‐based vascular brachytherapy source wire
Authors: Mourtada Firas A. , Soares Christopher G. , Seltzer Stephen M. , Lott Sam H.
Published: July 2002

Dosimetry measurements and Monte Carlo simulations for a catheter‐based endovascular brachytherapy source wire are described. The measured dose rates were obtained using both radiochromic dye film and an automated plastic scintillator. The investigated source has dimensions of 27 mm in length and 0.24 mm in diameter, and is encapsulated in NiTi. For the radiochromic film measurements, calibrated radiochromic dye film was irradiated at distances between 1 and 5 mm from the source axis in A‐150 plastic, and read out with a high‐resolution scanning densitometer. The depth‐dose curve measured in A‐150 is then converted to that in water using correction factors obtained from Monte Carlo calculations. For the scintillator system, direct measurements in water were acquired at distances between 1 and 6 mm from the center of the source, along the perpendicular bisector of the source axis. The scintillator was calibrated in terms of absorbed‐dose rate in a reference beta‐particle field at multiple depths. The measured dose rates obtained from the film and scintillator measurements were then normalized to the measured source activity, i.e., to convert the measured data to units of cGy/s/mCi. Theoretical dosimetry calculations of the catheter‐based wire geometry were also obtained from Monte Carlo simulations using the Electron Gamma Shower code (EGS4), the Monte Carlo N‐particle transport code (MCNP4B), and CYLTRAN from the Integrated Tiger Series codes (ITS v.3) and found to be in good agreement. The results of both measurements and calculations are expressed as absorbed‐dose rate in water per unit of contained activity (cGy/s/mCi). Comparisons indicate that the measured and calculated dosimetry are in good agreement (<10%) within the relevant treatment distances (1–5 mm). This work fully characterizes the radiation field around a novel beta brachytherapy source in water. The depth‐dose curve can be used to calculate the dose to the vessel wall from a 27 mm source wire centered within the vessel lumen.
Calculating dose distributions and wedge factors for photon treatment fields with dynamic wedges based on a convolution/superposition method
Authors: Liu H. Helen , McCullough Edwin C. , Mackie T. Rock
Published: July 2002

A convolution/superposition based method was developed to calculate dose distributions and wedge factors in photon treatment fields generated by dynamic wedges. This algorithm used a dual source photon beam model that accounted for both primary photons from the target and secondary photons scattered from the machine head. The segmented treatment tables (STT) were used to calculate realistic photon fluence distributions in the wedged fields. The inclusion of the extra‐focal photons resulted in more accurate dose calculation in high dose gradient regions, particularly in the beam penumbra. The wedge factors calculated using the convolution method were also compared to the measured data and showed good agreement within 0.5%. The wedge factor varied significantly with the field width along the moving jaw direction, but not along the static jaw or the depth direction. This variation was found to be determined by the ending position of the moving jaw, or the STT of the dynamic wedge. In conclusion, the convolution method proposed in this work can be used to accurately compute dose for a dynamic or an intensity modulated treatment based on the fluence modulation in the treatment field.
The radiation induced magnetic resonance image intensity change provides a more efficient three‐dimensional dose measurement in MRI–Fricke–agarose gel dosimetry
Authors: Chu W. C. , Guo W. Y. , Wu M. C. , Chung W. Y. , Pan David H. C.
Published: July 2002

A detailed methodology has been developed to map the spatial dose distribution in a Fricke–agarose gel based on the radiation induced image intensity change in the gel's magnetic resonance (MR) images. Besides the linear correlation between the change in the gel's spin‐lattice relaxation rate and the absorbed dose, it is shown here that the radiation induced image intensity change for ‐weighted spin‐echo images with correlates exponentially to the absorbed dose. Furthermore, at the lower dose region 15 Gy), the correlation is fairly linear and its sensitivity is high. The minimum detectable dose is shown to be equivalent to the one obtained using the conventional R1‐based approach. Since only one ‐weighted image is required for the dose evaluation, compared to the R1‐based method, the total MR imaging time can be reduced from hours to a few minutes. This extensive time reduction avoids ferric ion diffusion effects and provides a practical way to simply and effectively measure the three‐dimensional dose distribution using the Fricke–agarose dosimeter gel.
Intraoperative ultrasound for guidance and tissue shift correction in image‐guided neurosurgery
Authors: Comeau Roch M. , Sadikot Abbas F. , Fenster Aaron , Peters Terry M.
Published: July 2002

We present a surgical guidance system that incorporates pre‐operative image information (e.g., MRI) with intraoperative ultrasound (US) imaging to detect and correct for brain tissue deformation during image‐guided neurosurgery (IGNS). Many interactive IGNS implementations employ pre‐operative images as a guide to the surgeons throughout the procedure. However, when a craniotomy is involved, tissue movement during a procedure can be a significant source of error in these systems. By incorporating intraoperative US imaging, the target volume can be scanned at any time, and two‐dimensional US images may be compared directly to the corresponding slice from the pre‐operative image. Homologous points may be mapped from the intraoperative to the pre‐operative image space with an accuracy of better than 2 mm, enabling the surgeon to use this information to assess the accuracy of the guidance system along with the progress of the procedure (e.g., extent of lesion removal) at any time during the operation. Anatomical features may be identified on both the pre‐operative and intraoperative images and used to generate a deformation map, which can be used to warp the pre‐operative image to match the intraoperative US image. System validation is achieved using a deformable multi‐modality imaging phantom, and preliminary clinical results are presented.
Vowel perception by adults and children with normal language and specific language impairment: Based on steady states or transitions?
Authors: Sussman Joan E.
Published: July 2002

The current investigation studied whether adults, children with normally developing language aged 4–5 years, and children with specific language impairment, aged 5–6 years identified vowels on the basis of steady-state or transitional formant frequencies. Four types of synthetic tokens, created with a female voice, served as stimuli: (1) steady-state centers for the vowels [i] and [æ]; (2) voweless tokens with transitions appropriate for [bib] and [bæb]; (3) “congruent” tokens that combined the first two types of stimuli into [bib] and [bæb]; and (4) “conflicting” tokens that combined the transitions from [bib] with the vowel from [bæb] and vice versa. Results showed that children with language impairment identified the [i] vowel more poorly than other subjects for both the voweless and congruent tokens. Overall, children identified vowels most accurately in steady-state centers and congruent stimuli (ranging between 94%–96%). They identified the vowels on the basis of transitions only from “voweless” tokens with 89% and 83.5% accuracy for the normally developing and language impaired groups, respectively. Children with normally developing language used steady-state cues to identify vowels in 87% of the conflicting stimuli, whereas children with language impairment did so for 79% of the stimuli. Adults were equally accurate for voweless, steady-state, and congruent tokens (ranging between 99% to 100% accuracy) and used both steady-state and transition cues for vowel identification. Results suggest that most listeners prefer the steady state for vowel identification but are capable of using the onglide/offglide transitions for vowel identification. Results were discussed with regard to Nittrouer's developmental weighting shift hypothesis and Strange and Jenkin's dynamic specification theory.
On the modeling of narrow gaps using the standard boundary element method
Authors: Cutanda Vicente , Møller Juhl Peter , Jacobsen Finn
Published: July 2002

Numerical methods based on the Helmholtz integral equation are well suited for solving acoustic scattering and diffraction problems at relatively low frequencies. However, it is well known that the standard method becomes degenerate if the objects that disturb the sound field are very thin. This paper makes use of a standard axisymmetric Helmholtz integral equation formulation and its boundary element method (BEM) implementation to study the behavior of the method on two test cases: a thin rigid disk of variable thickness and two rigid cylinders separated by a gap of variable width. Both problems give rise to the same kind of degeneracy in the method, and modified formulations have been proposed to overcome this difficulty. However, such techniques are better suited for the so-called thin-body problem than for the reciprocal narrow-gap problem, and only the first is usually dealt with in the literature. A simple integration technique that can extend the range of thicknesses/widths tractable by the otherwise unmodified standard formulation is presented and tested. This technique is valid for both cases. The modeling of acoustic transducers like sound intensity probes and condenser microphones has motivated this work, although the proposed technique has a wider range of applications.
Two-tone suppression in the cricket, Eunemobius carolinus (Gryllidae, Nemobiinae)
Authors: Farris Hamilton E. , Hoy Ronald R.
Published: July 2002

Sounds with frequencies >15 kHz elicit an acoustic startle response (ASR) in flying crickets (Eunemobius carolinus). Although frequencies <15 kHz do not elicit the ASR when presented alone, when presented with ultrasound (40 kHz), low-frequency stimuli suppress the ultrasound-induced startle. Thus, using methods similar to those in masking experiments, we used two-tone suppression to assay sensitivity to frequencies in the audio band. Startle suppression was tuned to frequencies near 5 kHz, the frequency range of male calling songs. Similar to equal loudness contours measured in humans, however, equal suppression contours were not parallel, as the equivalent rectangular bandwidth of suppression tuning changed with increases in ultrasound intensity. Temporal integration of suppressor stimuli was measured using nonsimultaneous presentations of 5-ms pulses of 6 and 40 kHz. We found that no suppression occurs when the suppressing tone is >2 ms after and >5 ms before the ultrasound stimulus, suggesting that stimulus overlap is a requirement for suppression. When considered together with our finding that the intensity of low-frequency stimuli required for suppression is greater than that produced by singing males, the overlap requirement suggests that two-tone suppression functions to limit the ASR to sounds containing only ultrasound and not to broadband sounds that span the audio and ultrasound range.
Psychometric functions and temporal integration in electric hearing
Authors: Donaldson Gail S. , Viemeister Neal F. , Nelson David A.
Published: July 2002

Temporal-integration functions and psychometric functions for detection were obtained in eight users of the Nucleus 22-electrode cochlear implant. Stimuli were 100-Hz, 200-μs/phase trains of biphasic pulses with durations ranging from 0.44 to 630.44 ms (1 to 64 pulses). Temporal-integration functions were measured for 21 electrodes. Slopes of these functions were considerably shallower than the 2.5 dB/doubling slopes typically observed in acoustic hearing. They varied widely across subjects and for different electrodes in a given subject, ranging from 0.06 to 1.94 dB/doubling of stimulus pulses, with a mean [standard deviation (s.d.)] value of 0.42 (0.38). Psychometric functions were measured for 11 of the same 21 electrodes. Slopes of psychometric functions also varied across subjects and electrodes, and were 2–20 times steeper than those reported by other investigators for normal-hearing and cochlear-impaired acoustic listeners. Slopes of individual psychometric functions for 1-, 2-, 4-, and 8-pulse stimuli ranged from 0.20 to 1.84 log d/dB with a mean (s.d.) value of 0.77 (0.45). Psychometric-function slopes did not vary systematically with stimulus duration in most cases. A clear inverse relation between slopes of psychometric functions and slopes of temporal-integration functions was observed. This relation was reasonably well described by a hyperbolic function predicted by the multiple-looks model of temporal integration [Viemeister and Wakefield, J. Acoust. Soc. Am. 90, 858–865 (1991)]. Psychometric-function slopes tended to increase with absolute threshold and were inversely correlated with dynamic range, suggesting that observed differences in psychometric-function slopes across subjects and electrodes may reflect underlying differences in neural survival.
Effect of monaural and binaural altered auditory feedback on stuttering frequency
Authors: Stuart Andrew , Kalinowski Joseph , Rastatter Michael P.
Published: July 2002

The effect of monaural and binaural alterations in auditory feedback on stuttering frequency was investigated. Eleven participants who stutter read aloud under nonaltered auditory feedback (NAF) and monaural and binaural conditions of frequency altered feedback [(FAF), one-quarter octave shift upward] and delayed auditory feedback [(DAF), 50-ms delay] at a normal speech rate. Relative to the NAF condition, reductions in stuttering frequency of approximately 60%–75% were found with the altered auditory feedback conditions. Post hoc single-df comparisons revealed a reduction in stuttering frequency with altered auditory feedback versus NAF (p<0.0001), a greater reduction in stuttering frequency for binaural compared to monaural altered auditory feedback (p=0.028), and nonsignificant differences in stuttering frequencies for right versus left monaural conditions (p=0.54) and DAF versus FAF (p=0.70).
Measurement of distortion product phase in the ear canal of the cat
Authors: Fahey P. F. , Allen Jont B.
Published: July 2002

Amplitudes of odd order distortion products (DPs) that are detected in animal ear canals have been used to probe cochlear health, to search for cochlear amplification, and to measure aspects of cochlear mechanical frequency response. Like the DP amplitude, DP phase is also an important measure of the cochlear mechanical response. Reported here are measurements of DP phase in the ear canal of the cat. The phase data show frequency-dependent time delays. One of these delays is a function of f2, the frequency of the higher-frequency primary. Hence the DP phase φd is of the form φd=φ0+ωdτ, where ωd is the DP angular frequency and τ is a fixed time delay. Our results show that φd is independent of input level a2 as long as the ratio a2/a1⩽2, where a2 and a1 are the amplitudes of the input tones. As a2/a1 becomes greater than two, the fixed time delays increase for DPs whose frequencies are less than the frequencies of the input tones. When both levels are varied together the delay increases as the levels decrease. There can be phase changes as large as π associated with deep nulls in the DP magnitude for the two lower-frequency DPs. Features of the nulls may be modeled assuming that there is partial reflection of the DP wave from the DP place. The assumption of energy reemitted from the DP place also explains amplitude-ratio-dependent time delays and 2π level-dependent bifurcations in phase. The DP phase shows different dependencies for f2<1 kHz compared to f2>2 kHz.
Ambient noise imaging in warm shallow seas; second-order moment and model-based imaging algorithms
Authors: Potter John R. , Chitre Mandar
Published: July 2002

Ambient noise can be used to produce images of submerged objects using the mean intensity of the backscattered energy, a technique coined “acoustic daylight” because of its direct analogy to vision. It is suggested that there may be substantial additional information in higher moments of the data. At high frequencies (>10 kHz), absorption suppresses long-range propagation so that a received signal is largely dependent on the local geometry, source characteristics, and the scattering properties of interceding objects. It is shown that for snapping shrimp (Cragnon, Alpheus, and Synalpheus) illumination (the primary sources in warm shallow water above a few kHz), significant information is embodied in the second temporal moments of intensity. There is no visual analog to this concept, which suggests a broader imaging approach which may be termed ambient noise imaging (ANI). Another ANI technique explored is the use of spatial cross correlation, which works well and also has no visual analogy. A model-based processor (Kalman filter) is also applied to track targets subject to highly variable illumination such as provided by snapping shrimp. Examples are presented using data provided by Scripps Institution of Oceanography from the initial deployment of the Acoustic Daylight Ocean Noise Imaging System (ADONIS) in San Diego.
Viscoelastic Behavior of Polyethylene in Capillary Flow Expressed with Three Material Functions
Authors: Nakajima Nobuyuki , Shida Mitsuzo
Published: July 2002

It was shown that three material functions are required to relate various phenomena in the capillary flow of polyethylene. The phenomena examined are the entrance pressure loss, laminar flow through a capillary, memory decay in the flow, and extrudate swelling. A unified picture was constructed for the capillary flow and the energy balance was calculated.