bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptotic Protease Activating Factor 1 (Apaf-1)–Independent Cell Death Suppression by Bcl-2
Authors: Haraguchi Misako , Torii Seiji , Matsuzawa Shu-ichi , Xie Zhihua , Kitada Shinichi , Krajewski Stanislaw , Yoshida Hiroki , Mak Tak W. , Reed John C.
Published: July 2002

Reportedly, antiapoptotic Bcl-2 family proteins suppress apoptosis by binding to and inhibiting members of the CED-4 family of caspase activators. To explore this question, we used embryonic stem (ES) cells in which one (−/+) or both (−/−) copies of the gene encoding apoptotic protease activating factor 1 (Apaf-1), a CED-4 homologue, were disrupted by homologous recombination. Stable clones of heterozygous (−/+) and homozygous (−/−) Apaf-1 knockout ES cells that overexpressed Bcl-2 were generated. Withdrawal of serum growth factors or stimulation of heterozygous ES cells with staurosporine (STS), ultraviolet (UV)B irradiation, etoposide (VP16), or cisplatin induced apoptosis followed by cell death (determined by failure to exclude propidium iodide dye). These cell death stimuli also induced activation of several types of caspases and loss of mitochondrial membrane potential (ΔΨ) in heterozygous (+/−) Apaf-1 knockout ES cells. In addition, overexpression of Bcl-2 protected against these events in Apaf-1–expressing ES cells. In contrast, STS, UVB, and VP16 induced little or no caspase activation and apoptosis in homozygous (−/−) Apaf-1 knockout ES cells. Nevertheless, Apaf-1–deficient ES cells subjected to these cell death stimuli or deprived of growth factors did eventually die through a nonapoptotic mechanism associated with loss of ΔΨ. Moreover, Bcl-2 overprotection preserved ΔΨ, reduced the percentage of Apaf-1−/− ES cells undergoing cell death, and increased clonigenic survival. The extent of Bcl-2–mediated cytoprotection was not significantly different for heterozygous (−/+) versus homozygous (−/−) Apaf-1 knockout cells. Furthermore, although Bcl-2 could be readily coimmunoprecipitated with Bax, associations with Apaf-1 were undetectable under conditions where Apaf-1 interactions with procaspase-9 were observed. We conclude that Bcl-2 has cytoprotective functions independent of Apaf-1, preserving mitochondrial function through a caspase-independent mechanism.
Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis
Authors: Kima Peter E. , Constant Stephanie L. , Hannum Lynn , Colmenares Maria , Lee Karen S. , Haberman Ann M. , Shlomchik Mark J. , McMahon-Pratt Diane
Published: July 2002

We show here that maintenance of Leishmania infections with Leishmania mexicana complex parasites (Leishmania amazonensis and Leishmania pifanoi) is impaired in the absence of circulating antibody. In these studies, we used mice genetically altered to contain no circulating antibody, with and without functional B cells. This experimental design allowed us to rule out a critical role for B cell antigen presentation in Leishmania pathogenesis. In addition, we show that mice lacking the common γ chain of Fc receptors (FcγRI, FcεRI, and FcγRIII) are similarly refractory to infection with these parasites. These observations establish a critical role for antibody in the pathogenesis associated with infection by members of the L. mexicana complex.
Severe Lung Lesions Caused by Salmonella Are Prevented by Inhibition of the Contact System
Authors: Persson Kristin , Mörgelin Matthias , Lindbom Lennart , Alm Per , Björck Lars , Herwald Heiko
Published: July 2002

Vascular damage induced by trauma, inflammation, or infection results in an alteration of the endothelium from a nonactivated to a procoagulant, vasoconstrictive, and proinflammatory state, and can lead to life-threatening complications. Here we report that activation of the contact system by Salmonella leads to massive infiltration of red blood cells and fibrin deposition in the lungs of infected rats. These pulmonary lesions were prevented when the infected animals were treated with H-D-Pro-Phe-Arg-chloromethylketone, an inhibitor of coagulation factor XII and plasma kallikrein, suggesting that inhibition of contact system activation could be used therapeutically in severe infectious disease.
Cc Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis
Authors: Fife Brian T. , Huffnagle Gary B. , Kuziel William A. , Karpus William J.
Published: July 2002

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T lymphocyte–mediated disease of the central nervous system (CNS) characterized by mononuclear cell infiltration, demyelination, and paralysis. We previously demonstrated a role for chemokines in acute and relapsing EAE pathogenesis. Presently, we investigated the role of CC chemokine receptor 2 (CCR2) in acute EAE. CCR2−/− mice did not develop clinical EAE or CNS histopathology, and showed a significant reduction in T cell– and CNS-infiltrating CD45highF4/80+ monocyte subpopulations. Peripheral lymphocytes from CCR2−/− mice produced comparable levels of interferon-gamma (IFN-γ) and interleukin (IL)-2 in response to antigen-specific restimulation when compared with control mice. Adoptively transferred myelin oligodendrocyte glycoprotein 35-55–specific T cells lacking expression of CCR2 were able to induce EAE, whereas CCR2−/− recipients of wild-type T cells failed to develop disease. These results suggest that CCR2 expression on host-derived mononuclear cells is critical for disease induction.
B7H Costimulates Clonal Expansion of, and Cognate Destruction of Tumor Cells by, CD8+ T Lymphocytes In Vivo
Authors: Liu Xingluo , Bai Xue-Feng , Wen Jing , Gao Jian-Xin , Liu Jinqing , Lu Ping , Wang Yin , Zheng Pan , Liu Yang
Published: July 2002

B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulatory molecules and interacts with inducible costimulatory molecule (ICOS). Its function for CD8 T cells has not been reported. We report here that expression of B7H on the tumor cells reduced tumorigenicity and induced immunity to subsequent challenge with parental tumor cells. The immune protection correlates with an enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cells specific for tumor antigen P1A into mice that bore P1A-expressing tumors. We found that while the transgenic T cells divided faster in mice bearing the B7H+ tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7–1 and B7–2 on the endogenous host antigen-presenting cells (APCs). Interestingly, when B7H+ and B7H− tumors were coinjected, P1CTL selectively eliminated the B7H+ tumor cells. Moreover, B7H expressed on the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large tumor burdens. Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/or H-2Ld, the class I molecule that presents the P1A peptide. Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8+ T lymphocytes in vivo.
Essential Immunoregulatory Role for BCAP in B Cell Development and Function
Authors: Yamazaki Tetsuo , Takeda Kiyoshi , Gotoh Kumiko , Takeshima Hiroshi , Akira Shizuo , Kurosaki Tomohiro
Published: July 2002

BCAP was recently cloned as a binding molecule to phosphoinositide 3-kinase (PI3K). To investigate the role of BCAP, mutant mice deficient in BCAP were generated. While BCAP-deficient mice are viable, they have decreased numbers of mature B cells and B1 B cell deficiency. The mice produce lower titers of serum immunoglobulin (Ig)M and IgG3, and mount attenuated responses to T cell–independent type II antigen. Upon B cell receptor cross-linking, BCAP-deficient B cells exhibit reduced Ca2+ mobilization and poor proliferative responses. These findings demonstrate that BCAP plays a pivotal immunoregulatory role in B cell development and humoral immune responses.
Transient Receptor Potential 1 Regulates Capacitative Ca2+ Entry and Ca2+ Release from Endoplasmic Reticulum in B Lymphocytes
Authors: Mori Yasuo , Wakamori Minoru , Miyakawa Tomoya , Hermosura Meredith , Hara Yuji , Nishida Motohiro , Hirose Kenzo , Mizushima Akiko , Kurosaki Mari , Mori Emiko , Gotoh Kumiko , Okada Takaharu , Fleig Andrea , Penner Reinhold , Iino Masamitsu , Kurosaki Tomohiro
Published: July 2002

Capacitative Ca2+ entry (CCE) activated by release/depletion of Ca2+ from internal stores represents a major Ca2+ influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca2+ release-activated Ca2+ currents and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptor–mediated Ca2+ oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP3 receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca2+ signaling in B lymphocytes.
Identification of a Mutated Fibronectin As a Tumor Antigen Recognized by CD4+T Cells
Authors: Wang Helen Y. , Zhou Juhua , Zhu Kuichun , Riker Adam I. , Marincola Francesco M. , Wang Rong-Fu
Published: July 2002

CD4+ T cells play an important role in orchestrating host immune responses against cancer, particularly by providing critical help for priming and extending the survival of CD8+ T cells. However, relatively little is known about major histocompatibility complex class II–restricted human tumor antigens capable of activating CD4+ T cells. Here, we describe the identification of a mutated fibronectin (FN) as a tumor antigen recognized by human histocompatibility leukocyte antigen-DR2–restricted CD4+ T cells. Deoxyribonucleic acid (DNA) sequencing analysis indicated that this gene contains a mutation that results in the substitution of lysine for glutamic acid and gives rise to a new T cell epitope recognized by CD4+ T cells. Tumor cells harboring the mutant FN resulted in the loss of FN matrix formation and the gain of metastatic potential based on the migration pattern compared with that of tumor cells that express wild-type FN. Additional experiments using cell lines stably expressing the mutated FN cDNA demonstrated that the point mutation in FN was responsible for the loss of FN staining in extracellular matrices and the enhancement of tumor cell migration. These findings represent the first demonstration that a mutated gene product recognized by CD4+ T cells is directly involved in tumor metastasis, which indicates the importance of CD4+ T cells in controlling the spread of tumor cells to distant anatomic sites.
Opening Mechanism of a Cyclic Nucleotide–gated Channel Based on Analysis of Single Channels Locked in Each Liganded State
Authors: Ruiz MariaLuisa , Karpen Jeffrey W.
Published: July 2002

Cyclic nucleotide–gated channels contain four subunits, each with a binding site for cGMP or cAMP in the cytoplasmic COOH-terminal domain. Previous studies of the kinetic mechanism of activation have been hampered by the complication that ligands are continuously binding and unbinding at each of these sites. Thus, even at the single channel level, it has been difficult to distinguish changes in behavior that arise from a channel with a fixed number of ligands bound from those that occur upon the binding and unbinding of ligands. For example, it is often assumed that complex behaviors like multiple conductance levels and bursting occur only as a consequence of changes in the number of bound ligands. We have overcome these ambiguities by covalently tethering one ligand at a time to single rod cyclic nucleotide–gated channels (Ruiz, ML., and J.W. Karpen. 1997. Nature. 389:389–392). We find that with a fixed number of ligands locked in place the channel freely moves between three conductance states and undergoes bursting behavior. Furthermore, a thorough kinetic analysis of channels locked in doubly, triply, and fully liganded states reveals more than one kinetically distinguishable state at each conductance level. Thus, even when the channel contains a fixed number of bound ligands, it can assume at least nine distinct states. Such complex behavior is inconsistent with simple concerted or sequential allosteric models. The data at each level of liganding can be successfully described by the same connected state model (with different rate constants), suggesting that the channel undergoes the same set of conformational changes regardless of the number of bound ligands. A general allosteric model, which postulates one conformational change per subunit in both the absence and presence of ligand, comes close to providing enough kinetically distinct states. We propose an extension of this model, in which more than one conformational change per subunit can occur during the process of channel activation.
Linear functionals of eigenvalues of random matrices
Authors: Diaconis Persi , Evans Steven
Published: July 2002

Let

M
n

M_n

be a random

n
×
n

n \times n

unitary matrix with distribution given by Haar measure on the unitary group. Using explicit moment calculations, a general criterion is given for linear combinations of traces of powers of

M
n

M_n

to converge to a Gaussian limit as

n
→
∞

n \rightarrow \infty

. By Fourier analysis, this result leads to central limit theorems for the measure on the circle that places a unit mass at each of the eigenvalues of

M
n

M_n

. For example, the integral of this measure against a function with suitably decaying Fourier coefficients converges to a Gaussian limit without any normalisation. Known central limit theorems for the number of eigenvalues in a circular arc and the logarithm of the characteristic polynomial of

M
n

M_n

are also derived from the criterion. Similar results are sketched for Haar distributed orthogonal and symplectic matrices.
Katetov’s problem
Authors: Larson Paul , Todorcevic Stevo
Published: July 2002

In 1948 Miroslav Katětov showed that if the cube

X

3

X^{3}

of a compact space

X
X

satisfies the separation axiom T

5

_{5}

then

X
X

must be metrizable. He asked whether

X

3

X^{3}

can be replaced by

X

2

X^{2}

in this metrization result. In this note we prove the consistency of this implication.
Bounds for eigenvalues and condition numbers in the 𝑝-version of the finite element method
Authors: Hu Ning , Guo Xian-Zhong , Katz I.
Published: July 2002

In this paper, we present a theory for bounding the minimum eigenvalues, maximum eigenvalues, and condition numbers of stiffness matrices arising from the

p
p

-version of finite element analysis. Bounds are derived for the eigenvalues and the condition numbers, which are valid for stiffness matrices based on a set of general basis functions that can be used in the

p
p

-version. For a set of hierarchical basis functions satisfying the usual local support condition that has been popularly used in the

p
p

-version, explicit bounds are derived for the minimum eigenvalues, maximum eigenvalues, and condition numbers of stiffness matrices. We prove that the condition numbers of the stiffness matrices grow like

p

4
(
d
−
1
)

p^{4(d-1)}

, where

d
d

is the number of dimensions. Our results disprove a conjecture of Olsen and Douglas in which the authors assert that “regardless of the choice of basis, the condition numbers grow like

p

4
d

p^{4d}

or faster". Numerical results are also presented which verify that our theoretical bounds are correct.
Charakterformeln für Kipp-Moduln über Kac-Moody-Algebren
Authors: Soergel Wolfgang
Published: July 2002

We show how to express the characters of tilting modules in a (possibly parabolic) category

O

\mathcal {O}

over a Kac-Moody algebra in terms of the characters of simple highest weight modules. This settles in lots of cases Conjecture 7.2 in Kazhdan-Lusztig-Polynome und eine Kombinatorik für Kipp-Moduln, Represent. Theory (1997), by the author, describing the character of tilting modules for quantum groups at roots of unity.
TOPAL: recombination detection in DNA and protein sequences.
Authors: McGuire G , Wright F
Published: July 2002

SUMMARY: TOPAL scans a multiple sequence alignment for evidence of recombinant sequences, prior to phylogenetic analysis. AVAILABILITY: The TOPAL package may be accessed at http://www.bioss.sari.ac.uk/grainne, and by anonymous ftp at ftp.bioss. sari.ac.uk in the directory pub/phylogeny/topal. CONTACT: grainne@bioss.sari.ac.uk
History of the enzyme nomenclature system
Authors: Tipton Keith , Boyce Sinéad
Published: July 2002

Naming things is essential for people to understand one another, no matter what language or field of interest is involved. This is as true for enzymes, genes and chemicals as it is for birds, food, flowers, etc. Effective communication requires a lack of ambiguity, but, in practice, ambiguities abound even between people who use the same language in different parts of the world, or even within the same country. Whereas ambiguities in the words used for common objects or actions have been the basis for many, more-or-less memorable jokes, they can also cause a great deal of confusion. Such linguistic chaos is welcomed by many as being a part of a diverse heritage that should be preserved at all costs to prevent us from descending into Orwellian ‘newspeak’. However, in the sciences, there are distinct advantages in others being able to understand what one is doing. Many groups have stressed the need for standardized, universally accepted systems of nomenclature in chemistry, genetics, enzymology, etc. However, it is the universal acceptance that usually causes the problem. It is rare to find people who will admit that they find nomenclature to be an interesting subject, but many who profess contempt for it will get very excited if it is suggested that their pet nomenclature should be changed in the interest of clarity or uniformity. This account will consider the development of the enzyme nomenclature system, its benefits, shortcomings and future prospects.

Contact: ktipton@tcd.ie
The complexity of comparing reaction systems
Authors: Ettinger Mark
Published: July 2002

Motivation: As more genomic data becomes available there is increased attention on understanding the mechanisms encoded in the genome. New XML dialects like CellML and Systems Biology Markup Language (SBML) are being developed to describe biological networks of all types. In the absence of detailed kinetic information for these networks, stoichiometric data is an especially valuable source of information. Network databases are the next logical step beyond storing purely genomic information. Just as comparison of entries in genomic databases has been a vital algorithmic problem through the course of the sequencing project, comparison of networks in network databases will be a crucial problem as we seek to integrate higher-order network knowledge.

Results: We show that comparing the stoichiometric structure of two reactions systems is equivalent to the graph isomorphism problem. This is encouraging because graph isomorphism is, in practice, a tractable problem using heuristics. The analogous problem of searching for a subsystem of a reaction system is NP-complete. We also discuss heuristic issues in implementations for practical comparison of stoichiometric matrices.

Contact: ettinger@lanl.gov
EXAMINING THE WAGE DIFFERENTIAL FOR MARRIED AND COHABITING MEN
Authors: Stratton Leslie S.
Published: July 2002

Wage analyses indicate that married and cohabiting men earn more than do single, noncohabiting men. This article examines the nature of these wage differentials using data from the National Survey of Families and Households. Results indicate that the marital and cohabitation differentials are quite distinct. The higher wage observed for cohabiting men is driven primarily by selection and is eliminated by first differencing, but the higher wage observed for married men (and perhaps long‐term cohabiters) arises largely because of differential wage growth. Wages appear to rise more rapidly following marriage.
On Beauty … and the History of Business
Authors: Peiss Kathy
Published: July 2002

Beauty and business seem opposite terms but in fact have had an important and consequential relationship that business historians are only now exploring. This paper sketches several major themes and approaches to the topic. The first is the emergence of a large sector of the economy devoted to selling beauty aids, fashions, bodily care, and style to American women and men. Another is the deployment of beauty as a business strategy—in creating brands, sales, and marketing; in managing the workplace; and in projecting corporate identities. A third considers the sale of beauty itself, as a value added and attached to a wide range of goods, from art to bodies. These broad approaches suggest new directions for future research.
Determination of the antimicrobial susceptibilities of Canadian isolates of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis
Authors:   the Canadian Antimicrobial Study Group, Blondeau J. M. , Suter M. , Borsos S.
Published: July 2002

The susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae,Moraxella catarrhalis and Streptococcus pneumoniae) to several antimicrobial agents were tested by two different methods. β-Lactamase was produced by 68/211 (32.2%) of H. influenzae isolates and 64/75 (85.3%) of M. catarrhalis isolates. For S. pneumoniae, 19/156 (12.2%) isolates were resistant to penicillin (MIC ≥0.12 mg/L) and two isolates had MICs of 1.5 mg/L. For some combinations of agents and organisms, different methods gave different values for the proportion of isolates susceptible. Regardless of methodology, for H. influenzae, the most active antimicrobials based on proportion of strains susceptible were ciprofloxacin (100%) and cefpodoxime (98.5- 100%). For M. catarrhalis, the most active agents were azithromycin, cefaclor, cefixime, cefpodoxime, cefuroxime, ciprofloxacin, clarithromycin and loracarbef (100% each); the least active was ampicillin. Against penicillin-sensitive and -resistant pneumococci, the activity was not significantly different for azithromycin and clarithromycin (93.4- 100%) and ciprofloxacin (MIC 90 2.0 and 1.5 mg/L, respectively) but was different for cefuroxime (99.3% and 31.6%, respectively), cefaclor (MIC 90 0.75 and ≥256 mg/L, respectively), cefpodoxime (MIC 90 0.047 and 1.5 mg/L, respectively) and loracarbef (MIC 90 0.75 and ≥256 mg/L, respectively). This study indicates the increasing incidence, in Canada, of β-lactamase resistance in H. influenzae and M. catarrhalis and penicillin resistance in S. pneumoniae.
Clock-associated genes inArabidopsis: a family affair
Authors: Somers David E.
Published: July 2002

The identification of components of the plant circadian clock has been advanced recently with the success of two forward genetics approaches. TheZEITLUPEandTOC1loci were cloned and each was found to be part of two separate, larger gene families with intriguing domain structures. The ZTL family of proteins contains a subclass of the PAS domain coupled to an F box and kelch motifs, suggesting that they play a role in a novel light–regulated ubiquitination mechanism. TOC1 shares similarity to the receiver domain of the well–known two–component phosphorelay signalling systems, combined with a strong similarity to a region of the CONSTANS transcription factor, which is involved in controlling flowering time. When added to the repertoire of previously identified clock–associated genes, it is clear that both similarities and differences with other circadian systems will emerge in the coming years.
Multistep nucleus formation and a separate subunit contribution of the amyloidgenesis of heat‐denatured monellin
Authors: Konno Takashi
Published: July 2002

Monellin (MN) is a sweet‐tasting plant protein known to form fibrous aggregates in the heat‐denatured state. Here the amyloid‐type aggregation process of MN is extensively characterized. The amyloidgenesis was initiated in a highly denatured state of MN. A seeding effect of skipping a lag phase of the amyloid formation kinetics established a nucleation‐dependent aggregation mechanism. A finely controlled experimental protocol revealed an additional prenucleus stage preceding the maturation of the nucleus, indicating that the initial lag phase is composed of multiple conformational events. The results obtained for the aggregation properties of the separate A and B subunit chains of MN and a recombinant single‐chain MN suggest that the B chain exclusively contributed to the amyloid‐type aggregation. These findings suggest a scheme for the amyloidgenesis of MN and their subunits, and provide a unique model of amyloidgenesis that is regulated by the subunit composition of protein.
Digital subtraction peripheral angiography using image stacking: Initial clinical results
Authors: Kump Kenneth S. , Sachs Peter B. , Wilson David L.
Published: July 2002

Using clinically acquired x‐ray angiography image sequences, we compared three algorithms for creating a single diagnostic quality image that combined input images containing flowing contrast agent. These image‐stacking algorithms were: maximum opacity with the minimum gray‐scale value across time recorded at each spatial location, (REC) recursive temporal filtering followed by a maximum opacity operation, and (AMF) an approximate matched filter consisting of a convolution with a kernel approximating the matched filter followed by a maximum opacity operation. Eighteen clinical exams of the peripheral arteries of the legs were evaluated. AMF gave 2.7 times greater contrast to noise ratio than the single best subtraction image and 1.3 times improvement over REC, the second best stacking algorithm. This is consistent with previous simulations showing that AMF performs nearly equal to the optimal result from matched filtering without the well‐known limitations. For example, unlike matched filtering, AMF filter coefficients were obtained automatically using an image‐processing algorithm. AMF effectively brought out small collateral arteries, otherwise difficult to see, without degrading artery sharpness or stenosis grading. Comparing results using reduced and full contrast agent volumes demonstrated that contrast agent load could be reduced to one‐third of the conventional amount with AMF processing. By simulating reduced x‐ray exposures on clinical exams, we determined that x‐ray exposure could be reduced by 80% with AMF processing. We conclude that AMF is a promising, potential technique for reducing contrast agent load and for improving vessel visibility, both very important characteristics for vascular imaging.
A feasible method for clinical delivery verification and dose reconstruction in tomotherapy
Authors: Kapatoes J. M. , Olivera G. H. , Ruchala K. J. , Smilowitz J. B. , Reckwerdt P. J. , Mackie T. R.
Published: July 2002

Delivery verification is the process in which the energy fluence delivered during a treatment is verified. This verified energy fluence can be used in conjunction with an image in the treatment position to reconstruct the full three‐dimensional dose deposited. A method for delivery verification that utilizes a measured database of detector signal is described in this work. This database is a function of two parameters, radiological path‐length and detector‐to‐phantom distance, both of which are computed from a CT image taken at the time of delivery. Such a database was generated and used to perform delivery verification and dose reconstruction. Two experiments were conducted: a simulated prostate delivery on an inhomogeneous abdominal phantom, and a nasopharyngeal delivery on a dog cadaver. For both cases, it was found that the verified fluence and dose results using the database approach agreed very well with those using previously developed and proven techniques. Delivery verification with a measured database and CT image at the time of treatment is an accurate procedure for tomotherapy. The database eliminates the need for any patient‐specific, pre‐ or post‐treatment measurements. Moreover, such an approach creates an opportunity for accurate, real‐time delivery verification and dose reconstruction given fast image reconstruction and dose computation tools.
A semianalytic model to investigate the potential applications of x‐ray scatter imaging
Authors: Leclair Robert J. , Johns Paul C.
Published: July 2002

Although x‐ray scatter is generally regarded as a nuisance that reduces radiographic contrast and the signal‐to‐noise ratio (SNR) in conventional images, many technologies have been devised to extract useful information from the scattered x rays. A systematic approach, however, for analyzing the potential applications of x‐ray scatter imaging has been lacking. Therefore, we have formulated a simple but useful semianalytic model to investigate and SNR in scatter images. Our model considers the imaging of a target object against a background material of the same dimensions when both are situated within a water phantom. We have selected biological materials (liver, fat, bone, muscle, blood, and brain matter) for which intermolecular form factors for coherent scattering were available. Analytic relationships between and SNR were derived, and evaluated numerically as the target object thickness (0.01–40 mm) and photon energy (10–200 keV) were systematically varied. The fundamental limits of scatter imaging were assessed via calculations that assumed that all first‐order scatter exiting the phantom, over 4π steradians, formed the signal. Calculations for a restricted detector solid angle were then performed. For the task of imaging white brain matter versus blood in a 15 cm thick water phantom, the maximum SNR, over all energies, for images based on the detection of all forward scatter within the angular range 2°–12° is greater than that of primary images for target object thicknesses Use of the backscattered x rays within the range 158°–178° to image objects 3 cm below the surface of a 25 cm thick water phantom allows the liver to be distinguished from fat with a SNR superior to that of primary imaging when the objects are thick. Our analysis confirms the usefulness of scattered x rays, and provides simple methods for determining the regimes of medical interest in which x‐ray scatter imaging could outperform conventional imaging.
Room scattered neutrons
Authors: McCall Richard C. , McGinley Patton H. , Huffman Kristina E.
Published: July 2002

A method of evaluating the photoneutron fluence in the maze of accelerator facilities due to room scattered neutrons is presented. Measurements were made to demonstrate that the room scattered fluence is reduced by a factor of 2π in going from the treatment room to the inner maze entrance.
Interaural correlation sensitivity
Authors: Culling John F. , Colburn H. Steven , Spurchise Matthew
Published: July 2002

Sensitivity to differences in interaural correlation was measured for 1.3-ERB-wide bands of noise using a 2IFC task at six frequencies: 250, 500, 750, 1000, 1250, and 1500 Hz. The sensitivity index, d′, was measured for discriminations between a number of fixed pairs of correlation values. Cumulative d′ functions were derived for each frequency and condition. The d′ for discriminating any two values of correlation may be recovered from the cumulative d′ function by the difference between cumulative d′’s for these values. Two conditions were employed: the noisebands were either presented in isolation (narrow-band condition) or in the context of broad, contiguous flanking bands of correlated noise (fringed condition). The cumulative d′ functions showed greater sensitivity to differences in correlation close to 1 than close to 0 at low frequencies, but this difference was less pronounced in the fringed condition. Also, a more linear relationship was observed when cumulative d′ was plotted as a function of the equivalent signal-to-noise ratio (SNR) in dB for each correlation value, rather than directly against correlation. The equivalent SNR was the SNR at which the interaural correlation in an NoSπ stimulus would equal the interaural correlation of the noise used in the experiment. The maximum cumulative d′ declined above 750 Hz. This decline was steeper for the fringed than for the narrow-band condition. For the narrow-band condition, the total cumulative d′ was variable across listeners. All cumulative d′ functions were closely fitted using a simple two-parameter function. The complete data sets, averaged across listeners, from the fringed and narrow-band conditions were fitted using functions to describe the changes in these parameters over frequency, in order to produce an interpolated family of curves that describe sensitivity at frequencies between those tested. These curves predict the spectra recovered by the binaural system when complex sounds, such as speech, are masked by noise.
The harmonic-to-noise ratio applied to dog barks
Authors: Riede Tobias , Herzel Hanspeter , Hammerschmidt Kurt , Brunnberg Leo , Tembrock Günter
Published: July 2002

Dog barks are typically a mixture of regular components and irregular (noisy) components. The regular part of the signal is given by a series of harmonics and is most probably due to regular vibrations of the vocal folds, whereas noise refers to any nonharmonic (irregular) energy in the spectrum of the bark signal. The noise components might be due to chaotic vibrations of the vocal-fold tissue or due to turbulence of the air. The ratio of harmonic to nonharmonic energy in dog barks is quantified by applying the harmonics-to-noise ratio (HNR). Barks of a single dog breed were recorded in the same behavioral context. Two groups of dogs were considered: a group of ten healthy dogs (the normal sample), and a group of ten unhealthy dogs, i.e., dogs treated in a veterinary clinic (the clinic sample). Although the unhealthy dogs had no voice disease, differences in emotion or pain or impacts of surgery might have influenced their barks. The barks of the dogs were recorded for a period of 6 months. The HNR computation is based on the Fourier spectrum of a 50-ms section from the middle of the bark. A 10-point moving average curve of the spectrum on a logarithmic scale is considered as estimator of the noise level in the bark, and the maximum difference of the original spectrum and the moving average is defined as the HNR measure. It is shown that a reasonable ranking of the voices is achievable based on the measurement of the HNR. The HNR-based classification is found to be consistent with perceptual evaluation of the barks. In addition, a multiparametric approach confirms the classification based on the HNR. Hence, it may be concluded that the HNR might be useful as a novel parameter in bioacoustics for quantifying the noise within a signal.
High-speed digital imaging of the medial surface of the vocal folds
Authors: Berry David A. , Montequin Douglas W. , Tayama Niro
Published: July 2002

High-speed digital imaging of the medial surface of the vocal folds was performed in excised canine larynx experiments. Building on the excised larynx investigations of Baer [Ph.D. dissertation, MIT, Boston, MA (1975)] and hemilarynx investigations of Jiang and Titze [Laryngoscope 103, 872–882 (1993)], nine vocal fold fleshpoints were tracked simultaneously along the medial surface of one coronal plane of the left vocal fold using a Kodak EktaPro 4540 high-speed digital imaging system. By imaging from two distinct views, 3D reconstructions of fleshpoint trajectories were performed with a sampling frequency of 4.5 kHz and a spatial resolution of approximately 0.08 mm. Quantitative results were derived from a typical example of periodic chestlike vibrations. Furthermore, these data were decomposed into empirical eigenfunctions, the building blocks of vocal fold vibration, illuminating basic mechanisms of self-sustained oscillation. Previously, such mechanisms have only been explored theoretically using computer models of vocal fold vibration [Berry et al., J. Acoust. Soc. Am. 95, 3595–3604 (1994)]. Similar to the theoretical studies, two eigenfunctions captured 98% of the variance of the data. Because this investigation utilized high-speed technology, the methodology may also be used to examine complex, aperiodic vibrations. Thus, this technique allows mechanisms of regular and irregular vocal fold vibration to be explored using direct observations of vibrating tissues in the laboratory.
On the complex conjugate roots of the Rayleigh equation: The leaky surface wave
Authors: Schröder Christoph T. , Scott Waymond R.
Published: July 2002

In recent experiments and numerical studies, a leaky surface wave has been observed at the surface of an isotropic homogeneous elastic solid. This paper gives a detailed description of this leaky surface wave and explains its origin from the fundamental differential equations. Theoretically, the leaky surface wave arises from the complex conjugate roots of the Rayleigh equation. The complex conjugate roots give rise to a wave that propagates along the surface and is coupled to a plane shear wave in the medium. Due to the coupling, the surface wave leaks energy into the medium and is highly inhomogeneous. Its particle motion at the surface is prograde in nature, distinguishing it from the well-known Rayleigh surface wave which causes a retrograde particle motion.
Observations on attenuation and shear-wave velocity in fine-grained, marine sediments
Authors: Bowles Frederick A.
Published: July 2002

Compressional(P)-wave attenuation, shear(S)-wave attenuation, and shear(S)-wave velocity measurements, compiled for fine-grained, unconsolidated sediments, show trends that do not support empirical relationships [Hamilton, J. Acoust. Soc. Am. 68, 1313–1340 (1980); in Acoustics and Ocean Bottom (F. A. S. E. Specialize Conf., Madrid, 1987)] commonly used for geoacoustic modeling. The exception is compressional-wave attenuation data, from 10 Hz to 500 kHz, that essentially follow a frequency dependence of f1 (±2 standard deviations). P-wave attenuation with depth is difficult, if not impossible, to predict given the variability in the data. Examination of several attenuation/depth profiles indicates that those of Mitchell and Focke [J. Acoust. Soc. Am. 67, 1582–1589 (1980)] may be the best choice for predicting P-wave attenuation with depth at the present time. The assumption that S-wave and P-wave attenuations are proportional [Hamilton, J. Acoust. Soc. Am. 60, 334–338 (1976c); in Acoustics and Ocean Bottom (F. A. S. E. Specialize Conf., Madrid, 1987)] is not supported by the data. S-wave attenuations calculated from effective stress mimmick the data, however, suggesting this as a better method for predicting S-wave attenuation with depth. S-wave velocity/depth profiles fall into high- and low-velocity groups that (1) reflect gross differences in sediment texture, and (2) demonstrate the importance of sediment characterization in order to select an appropriate velocity/depth function.
An integral equation formulation for boundary element analysis of propagation in viscothermal fluids
Authors: Karra C. , Tahar M. Ben
Published: July 2002

A new variational formulation using integral equations for the resolution of a propagation problem in a viscous and thermally conducting fluid is investigated. Numerical techniques are applied to a geometry of revolution. Results are compared to an analytic solution for a cylindrical cavity filled with air. These results illustrate the effects of viscosity and thermal conductivity of air in the case of micro cavities.
Separation of interfering acoustic scattered signals using the invariants of the time-reversal operator. Application to Lamb waves characterization
Authors: Prada Claire , Fink Mathias
Published: July 2002

The D.O.R.T. method (in French, Décomposition de l’Opérateur de Retournement Temporel) is a scattering analysis technique using arrays of transducers. The method was shown to be effective in detecting and focusing on pointlike scatterers in Prada et al. [J. Acoust Soc. Am. 99, 2067–2076 (1996)]. Here the D.O.R.T. method is extended to other geometries, applying it to an air-filled cylindrical shell embedded in water. It is shown that the diagonalization of the time-reversal operator permits the various elastic components of the scattered field to be extracted. For the considered cylinder, these components are mainly three circumferential waves (A0, A1, and S0 Lamb modes). Each Lamb mode is shown to correspond to an invariant of the time-reversal operator. The dispersion curves of these waves are calculated from the invariants. In particular, the cutoff frequency of the A1 mode is found and provides the thickness of the shell. Finally, resonance frequencies of the shell are deduced from the frequency dependence of the eigenvalues of the time-reversal operator.
Lateralization of large interaural delays
Authors: Mossop Jennifer E. , Culling John F.
Published: July 2002

Two experiments explored the limits of listeners’ abilities to interpret large interaural time delays (ITDs) in terms of laterality. In experiment 1, just-noticeable differences (jnd’s) were measured, using an adaptive procedure, for various reference ITDs of Gaussian noise between 0 and 3000 μs. The jnd’s increased gradually with reference ITD for reference ITDs between 0 μs and 700 μs, then rose sharply to plateau at much higher jnd’s for the remainder of the standard ITDs tested (1000–3000 μs). The second experiment tested left/right discrimination of Gaussian noise that was interaurally delayed up to 10 000 μs, and high-pass filtered to cutoff frequencies between 0 Hz (broadband) and 3000 Hz. There was good discrimination (62%; significantly above chance, p<0.05) for broadband and 500-Hz high-pass cutoff stimuli for all ITDs up to 10 000 μs, and for ITDs up to at least 3000 μs for higher high-pass cutoff frequencies. These results indicate that laterality cues are discriminable at much larger ITDs than are experienced in free-field listening, even in the absence of energy below 3 kHz.
Perturbation-free measurement of the harmonics-to-noise ratio in voice signals using pitch synchronous harmonic analysis
Authors: Murphy Peter J.
Published: July 2002

The measurement of the harmonics-to-noise ratio (HNR) in speech signals gives an indication of the aperiodicity of the speech waveform. This may be due to the presence of jitter, shimmer, additive noise, waveshape change, or some unknown combination of these factors. In order to estimate the HNR as a measure of the additive noise component only, the contaminating effects of the other contributory components must first be removed. A pitch synchronous harmonic analysis is proposed to overcome this problem. The procedure takes advantage of the time scale compression–frequency expansion property of the Fourier series in order to eliminate jitter and shimmer. Successive spectra are added by harmonic number as opposed to frequency location, and perturbation is removed due to the fact that the relative heights of the harmonic components remain the same for scaled signals. The technique is examined on synthetically generated voice signals. A discussion of the results is given in terms of human voice signals, characterization of jitter, vocal tract filtering effects, perturbation mechanisms, nonlinear dynamics, and the possibility of developing the method for use with inverse filtering strategies.
Recognition of spoken words by native and non-native listeners: Talker-, listener-, and item-related factors
Authors: Bradlow Ann R. , Pisoni David B.
Published: July 2002

In order to gain insight into the interplay between the talker-, listener-, and item-related factors that influence speech perception, a large multi-talker database of digitally recorded spoken words was developed, and was then submitted to intelligibility tests with multiple listeners. Ten talkers produced two lists of words at three speaking rates. One list contained lexically “easy” words (words with few phonetically similar sounding “neighbors” with which they could be confused), and the other list contained lexically “hard” words (words with many phonetically similar sounding “neighbors”). An analysis of the intelligibility data obtained with native speakers of English (experiment 1) showed a strong effect of lexical similarity. Easy words had higher intelligibility scores than hard words. A strong effect of speaking rate was also found whereby slow and medium rate words had higher intelligibility scores than fast rate words. Finally, a relationship was also observed between the various stimulus factors whereby the perceptual difficulties imposed by one factor, such as a hard word spoken at a fast rate, could be overcome by the advantage gained through the listener’s experience and familiarity with the speech of a particular talker. In experiment 2, the investigation was extended to another listener population, namely, non-native listeners. Results showed that the ability to take advantage of surface phonetic information, such as a consistent talker across items, is a perceptual skill that transfers easily from first to second language perception. However, non-native listeners had particular difficulty with lexically hard words even when familiarity with the items was controlled, suggesting that non-native word recognition may be compromised when fine phonetic discrimination at the segmental level is required. Taken together, the results of this study provide insight into the signal-dependent and signal-independent factors that influence spoken language processing in native and non-native listeners.
A time domain rough surface scattering model based on wedge diffraction: Application to low-frequency backscattering from two-dimensional sea surfaces
Authors: Keiffer Richard S. , Novarini Jorge C.
Published: July 2002

A time domain method for calculating the acoustic impulse response of impenetrable, rough, two-dimensional (2D) surfaces is presented. The method is based on an extension of the wedge assemblage (WA) method to 2D surfaces and objects. Like the WA method for one-dimensional (1D) surfaces, the approach for 2D surfaces uses Biot’s and Tolstoy’s exact solution for the impulse response of an infinite impenetrable wedge [J. Acoust. Soc. Am. 29, 381–391 (1957)] as its fundamental building block. The validity of the WA method for backscattering from 2D sea surfaces is assessed through comparisons with calculations based on Milder’s operator expansion (OE) method [J. Acoust. Soc. Am. 89, 529–541 (1991)]. Average intensities for backscattering from 2D fully developed seas (20 m/s wind speed) were computed by the WA and OE methods using 50 surface realizations and compared at 11 frequencies between 100 and 200 Hz. A single, moderately low grazing angle of incidence (20°) and several scattered grazing angles (90°, 45°, 20°, and 10°) were considered. Excellent overall agreement between the two models was obtained. The utility of the WA method as a tool to describe the physics of the scattering process is also discussed.