bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM
Authors: Smith Graeme C. M. , Cary Robert B. , Lakin Nicholas D. , Hann Byron C. , Teo Soo-Hwang , Chen David J. , Jackson Stephen P.
Published: July 2002

The human neurodegenerative and cancer predisposition condition ataxia-telangiectasia is characterized at the cellular level by radiosensitivity, chromosomal instability, and impaired induction of ionizing radiation-induced cell cycle checkpoint controls. Recent work has revealed that the gene defective in ataxia-telangiectasia, termed
ATM
, encodes an ≈350-kDa polypeptide, ATM, that is a member of the phosphatidylinositol 3-kinase family. We show that ATM binds DNA and exploit this to purify ATM to near homogeneity. Atomic force microscopy reveals that ATM exists in two populations, with sizes consistent with monomeric and tetrameric states. Atomic force microscopy analyses also show that ATM binds preferentially to DNA ends. This property is similar to that displayed by the DNA-dependent protein kinase catalytic subunit, a phosphatidylinositol 3-kinase family member that functions in DNA damage detection in conjunction with the DNA end-binding protein Ku. Furthermore, purified ATM contains a kinase activity that phosphorylates serine-15 of p53 in a DNA-stimulated manner. These results provide a biochemical assay system for ATM, support genetic data indicating distinct roles for DNA-dependent protein kinase and ATM, and suggest how ATM may signal the presence of DNA damage to p53 and other downstream effectors.
The topomer-sampling model of protein folding
Authors: Debe Derek A. , Carlson Matt J. , Goddard William A.
Published: July 2002

Clearly, a protein cannot sample all of its conformations (e.g., ≈3
100
≈ 10
48
for a 100 residue protein) on an
in vivo
folding timescale (<1 s). To investigate how the conformational dynamics of a protein can accommodate subsecond folding time scales, we introduce the concept of the native topomer, which is the set of all structures similar to the native structure (obtainable from the native structure through local backbone coordinate transformations that do not disrupt the covalent bonding of the peptide backbone). We have developed a computational procedure for estimating the number of distinct topomers required to span all conformations (compact and semicompact) for a polypeptide of a given length. For 100 residues, we find ≈3 × 10
7
distinct topomers. Based on the distance calculated between different topomers, we estimate that a 100-residue polypeptide diffusively samples one topomer every ≈3 ns. Hence, a 100-residue protein can find its native topomer by random sampling in just ≈100 ms. These results suggest that subsecond folding of modest-sized, single-domain proteins can be accomplished by a two-stage process of (
i
) topomer diffusion: random, diffusive sampling of the 3 × 10
7
distinct topomers to find the native topomer (≈0.1 s), followed by (
ii
) intratopomer ordering: nonrandom, local conformational rearrangements within the native topomer to settle into the precise native state.
The reversible condensation and expansion of the rotavirus genome
Authors: Pesavento Joseph B. , Lawton Jeffrey A. , Estes Mary K. , Prasad B. V. Venkataram
Published: July 2002

Understanding the structural organization of the genome is
particularly relevant in segmented double-stranded RNA viruses, which
exhibit endogenous transcription activity. These viruses
are molecular machines capable of repeated cycles of transcription
within the intact capsid. Rotavirus, a major cause of infantile
gastroenteritis, is a prototypical segmented double-stranded RNA virus.
From our three-dimensional structural analyses of rotavirus examined
under various chemical conditions using electron cryomicroscopy, we
show here that the viral genome exhibits a remarkable conformational
flexibility by reversibly changing its packaging density. In the
presence of ammonium ions at high pH, the genome condenses to a radius
of ≈180 Å from ≈220 Å. Upon returning to physiological
conditions, the genome re-expands and fully maintains its
transcriptional properties. These studies provide further insights into
the genome organization and suggest that the observed isometric and
concentric nature of the condensation is due to strong interactions
between the genome core and the transcription enzymes anchored to the
capsid inner surface. The ability of the genome to condense beyond what
is normally observed in the native virus indicates that the negative
charges on the RNA in the native state may be only partially
neutralized. Partial neutralization may be required to maintain
appropriate interstrand spacing for templates to move around the enzyme
complexes during transcription. Genome condensation was not observed
either with increased cation concentrations at normal pH or at high pH
without ammonium ions. This finding indicates that the observed genome
condensation is a synergistic effect of hydroxyl and ammonium ions
involving disruption of protein–RNA interactions that perhaps
facilitate further charge neutralization and consequent reduction in
the interstrand spacing.
Prediction of Treatment Outcomes: Lifetime Depression versus the Continuum of Care
Authors: Miller Norman S. , Ninonuevo Fred , Hoffmann Norman G. , Astrachan Boris M.
Published: July 2002

We sought to determine the impact of a lifetime diagnosis of major depression on addiction treatment outcome. Structured interviews were conducted upon admission, and consecutive structured interviews were conducted prospectively for treatment outcome at 6 and 12 month follow‐up periods. A multisite evaluation study of patients undergoing addiction treatment for alcohol and drug dependence was conducted in private outpatient facilities. Two thousand twenty‐nine subjects from 33 independent programs were enrolled in a national registry for addiction treatment outcomes. The patients received abstinence‐based addiction treatment with referral to a 12‐step recovery program, often Alcoholics Anonymous, and continuing care in the treatment programs. The outcome areas measured were treatment completion, posttreatment substance use, exposure to psychosocial relapse risk factors, involvement with continuing care (formal aftercare and peer support groups), and posttreatment vocational functioning, health care utilization, and legal involvement. The prevalence rate of depressive symptoms over at least a 2‐week period (major depression) in our sample was 28%. Multivariate analysis with stepwise multiple regression indicated that the most powerful predictors (relatively) of posttreatment alcohol/drug use were peer support group attendance and program continuing care involvement. Lifetime depression by itself and in interaction with each of these factors accounted for less than 2% of the variance in outcome. Logistic regression yielded similar results in the prediction of abstinence versus relapse. Posttreatment more than pretreatment factors appear to be more decisive in predicting risk for relapse.
Modulation of Glutamate Generation in Mitochondria Affects Hormone Secretion in INS‐1E Beta Cells
Authors: Maechler Pierre , Antinozzi Peter A. , Wollheim Claes B.
Published: July 2002

The mitochondria play a pivotal role in regulating glucose induced insulin secretion in the pancreatic beta cell. We have recently demonstrated that glutamate derived from mitochondria participates directly in the stimulation of insulin exocytosis. In the present study, mitochondria isolated from the beta cell line INS1E generated glutamate when incubated with the tricarboxylic acid cycle intermediate succinate. The generation of glutamate correlated with stimulated mitochondrial activity monitored as oxygen consumption and was inhibited by the mitochondrial uncoupler carbonyl cyanide p
Dynamics of the Genome during Early Xenopus laevis Development: Karyomeres As Independent Units of Replication
Authors: Lemaitre Jean-Marc , Géraud Gérard , Méchali Marcel
Published: July 2002

During Xenopus laevis early development, the genome is replicated in less than 15 min every 30 min. We show that during this period, DNA replication proceeds in an atypical manner. Chromosomes become surrounded by a nuclear membrane lamina forming micronuclei or karyomeres. This genomic organization permits that prereplication centers gather on condensed chromosomes during anaphase and that DNA replication initiates autonomously in karyomeres at early telophase before nuclear reconstruction and mitosis completion. The formation of karyomeres is not dependent on DNA replication but requires mitotic spindle formation and the normal segregation of chromosomes. Thus, during early development, chromosomes behave as structurally and functionally independent units. The formation of a nuclear envelope around each chromosome provides an in vivo validation of its role in regulating initiation of DNA replication, enabling the rate of replication to accelerate and S phase to overlap M phase without illegitimate reinitiation. The abrupt disappearance of this atypical organization within one cell cycle after thirteen divisions defines a novel developmental transition at the blastula stage, which may affect both the replication and the transcription programs of development.
A Specific Role of Phosphatidylinositol 3–Kinase γ
Authors: Bony Claire , Roche Serge , Shuichi Ueno , Sasaki Takehiko , Crackower Michael A. , Penninger Josef , Mano Hiroyuki , Pucéat Michel
Published: July 2002

Purinergic stimulation of cardiomyocytes turns on a Src family tyrosine kinase–dependent pathway that stimulates PLCγ and generates IP3, a breakdown product of phosphatidylinositol 4,5–bisphosphate (PIP2). This signaling pathway closely regulates cardiac cell autonomic activity (i.e., spontaneous cell Ca2+ spiking). PIP2 is phosphorylated on 3′ by phosphoinositide 3–kinases (PI3Ks) that belong to a broad family of kinase isoforms. The product of PI3K, phosphatidylinositol 3,4,5–trisphosphate, regulates activity of PLCγ. PI3Ks have emerged as crucial regulators of many cell functions including cell division, cell migration, cell secretion, and, via PLCγ, Ca2+ homeostasis. However, although PI3Kα and -β have been shown to mediate specific cell functions in nonhematopoietic cells, such a role has not been found yet for PI3Kγ.

We report that neonatal rat cardiac cells in culture express PI3Kα, -β, and -γ. The purinergic agonist predominantly activates PI3Kγ. Both wortmannin and LY294002 prevent tyrosine phosphorylation, and membrane translocation of PLCγ as well as IP3 generation in ATP-stimulated cells. Furthermore, an anti-PI3Kγ, but not an anti-PI3Kβ, injected in the cells prevents the effect of ATP on cell Ca2+ spiking. A dominant negative mutant of PI3Kγ transfected in the cells also exerts the same action. The effect of ATP was observed on spontaneous Ca2+ spiking of wild-type but not of PI3Kγ2/2 embryonic stem cell–derived cardiomyocytes. ATP activates the Btk tyrosine kinase, Tec, and induces its association with PLCγ. A dominant negative mutant of Tec blocks the purinergic effect on cell Ca2+ spiking. Tec is translocated to the T-tubes upon ATP stimulation of cardiac cells. Both an anti-PI3Kγ antibody and a dominant negative mutant of PI3Kγ injected or transfected into cells prevent the latter event.

We conclude that PI3Kγ activation is a crucial step in the purinergic regulation of cardiac cell spontaneous Ca2+ spiking. Our data further suggest that Tec works in concert with a Src family kinase and PI3Kγ to fully activate PLCγ in ATP-stimulated cardiac cells. This cluster of kinases provides the cardiomyocyte with a tight regulation of IP3 generation and thus cardiac autonomic activity.
Degradation of Transcription Factor Rfx5 during the Inhibition of Both Constitutive and Interferon γ–Inducible Major Histocompatibility Complex Class I Expression in Chlamydia-Infected Cells
Authors: Zhong Guangming , Liu Li , Fan Tao , Fan Peiyi , Ji Hezhao
Published: July 2002

We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-γ–inducible major histocompatibility complex (MHC) class II expression in infected cells by degrading upstream stimulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-γ–inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well with degradation of RFX5, an essential downstream transcription factor required for both the constitutive and IFN-γ–inducible MHC class I expression. We further demonstrate that a lactacystin-sensitive proteasome-like activity identified in chlamydia-infected cell cytosolic fraction can degrade both USF-1 and RFX5. This proteasome-like activity is dependent on chlamydial but not host protein synthesis. Host preexisting proteasomes may not be required for the unique proteasome-like activity. These observations suggest that chlamydia-secreted factors may directly participate in the proteasome-like activity. Efforts to identify the chlamydial factors are underway. These findings provide novel information on the molecular mechanisms of chlamydial evasion of host immune recognition.
H2-DMα−/− Mice Show the Importance of Major Histocompatibility Complex–Bound Peptide in Cardiac Allograft Rejection
Authors: Felix Nathan J. , Brickey W. June , Griffiths Robert , Zhang Jinghua , Van Kaer Luc , Coffman Thomas , Ting Jenny P.-Y.
Published: July 2002

The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DMα−/− mice. These mice have predominantly class II–associated invariant chain peptide (CLIP)-, not antigenic peptide–bound, MHC class II. H2-DMα−/− donor heart grafts survived three times longer than wild-type grafts and slightly longer than I-Aβb−/− grafts. Proliferative T cell response was absent, and cytolytic response was reduced against the H2-DMα−/− grafts in vivo. Residual cytolytic T cell and antibody responses against intact MHC class I lead to eventual rejection. Removal of both H2-DMα and β2-microglobulin (β2m) in cardiac grafts lead to greater (8–10 times) graft survival, whereas removal of β2m alone did not have any effect. These results demonstrate the significance of peptide rather than just allogeneic MHC, in eliciting graft rejection.
HIV-1 Nef Interacts with Inositol Trisphosphate Receptor to Activate Calcium Signaling in T Cells
Authors: Manninen Aki , Saksela Kalle
Published: July 2002

HIV-1 pathogenicity factor Nef has been shown to modulate calcium signaling in host cells, but the underlying molecular mechanisms have remained unclear. Here we show that calcium/calcineurin-dependent activation of nuclear factor of activated T cells (NFAT) by Nef in Jurkat T cells requires the endoplasmic reticulum-resident inositol trisphosphate receptor (IP3R), but yet does not involve increase in phospholipase-Cγ1 (PLCγ1)-catalyzed production of IP3 or depletion of IP3-regulated intracellular calcium stores. Nef could be coprecipitated with endogenous IP3R type-1 (IP3R1) from Nef-transfected Jurkat T cells as well as from HIV-infected primary human peripheral mononuclear cells. Thus, the Nef/IP3R1-interaction defines a novel T cell receptor–independent mechanism by which Nef can promote T cell activation, and appears to involve atypical IP3R-triggered activation of plasma membrane calcium influx channels in a manner that is uncoupled from depletion of intracellular calcium stores.
Methanethiosulfonate Derivatives Inhibit Current through the Ryanodine Receptor/Channel
Authors: Quinn Kerry E. , Ehrlich Barbara E.
Published: July 2002

To identify regions of the ryanodine receptor (RyR) important for ion conduction we modified the channel with sulfhydryl-reacting compounds. After addition of methanethiosulfonate (MTS) compounds channel conductance was decreased while other channel properties, including channel regulation by ATP, caffeine, or Ca, were unaffected. The site of action was accessible to the MTS compounds from the cytoplasmic, but not the luminal, side of the channel. In addition, the hydrophilic MTS compounds were only effective when the channel was open, suggesting that the compounds covalently modify the channel from within the water-filled ion conducting pathway. The decrease in channel current amplitude occurred in a step-wise fashion and was irreversible and cumulative over time, eventually leading to the complete block of channel current. However, the time required for each consecutive modification during continuous exposure to the MTS compounds increased, suggesting that successive modification by the MTS compounds is not independent. These results are consistent with the hypothesis that the channel forms a wide vestibule on the cytoplasmic side and contains a much smaller opening on the luminal side. Furthermore, our results indicate that the MTS compounds can serve as functional markers for specific residues of the RyR to be identified in molecular studies.
Pure product polynomials and the Prouhet-Tarry-Escott problem
Authors: Maltby Roy
Published: July 2002

An

n
n

-factor pure product is a polynomial which can be expressed in the form

∏

i
=
1

n

(
1
−

x

α
i

)

\prod _{i=1}^n(1-x^{\alpha _i})

for some natural numbers

α
1

,
…
,

α
n

\alpha _1,\ldots ,\alpha _n

. We define the norm of a polynomial to be the sum of the absolute values of the coefficients. It is known that every

n
n

-factor pure product has norm at least

2
n

2n

. We describe three algorithms for determining the least norm an

n
n

-factor pure product can have. We report results of our computations using one of these algorithms which include the result that every

n
n

-factor pure product has norm strictly greater than

2
n

2n

if

n
n

is

7
7

,

9
9

,

10
10

, or

11
11

.
The discrete Plateau Problem: Algorithm and numerics
Authors: Dziuk Gerhard , Hutchinson John
Published: July 2002

We solve the problem of finding and justifying an optimal fully discrete finite element procedure for approximating minimal, including unstable, surfaces. In this paper we introduce the general framework and some preliminary estimates, develop the algorithm, and give the numerical results. In a subsequent paper we prove the convergence estimate. The algorithmic procedure is to find stationary points for the Dirichlet energy within the class of discrete harmonic maps from the discrete unit disc such that the boundary nodes are constrained to lie on a prescribed boundary curve. An integral normalisation condition is imposed, corresponding to the usual three point condition. Optimal convergence results are demonstrated numerically and theoretically for nondegenerate minimal surfaces, and the necessity for nondegeneracy is shown numerically.
Seasonal variations in exposure to microbial cell wall components among household waste collectors
Authors: Thorn Jörgen
Published: July 2002

Background: Collection, separation, and composting of household waste generates organic dusts that may contain the inflammagenic agent endotoxin and (1→3)-ß-D-glucan, a cell wall component of fungi, plants and certain bacteria. In previous studies, waste collectors have reported a greater number of or more severe symptoms in the summer. To further elucidate whether a seasonal variation in exposure could support previous findings of the presence of symptoms during summer months, a study was performed to assess exposures to airborne (1→3)-ß-D-glucan and endotoxin during different seasons among household waste collectors handling compostable waste.

Methods: Measurements were made of the amounts of airborne (1→3)-ß-D-glucan and endotoxin using personal sampler equipment in two household waste collectors handling compostable waste. Measurements were made every second week from September 1998 to January 2000.

Results: The amounts of airborne endotoxin were low during the study period. The amount of airborne (1→3)-ß-D-glucan was higher during the warm season, and there was a relationship between exposure levels of (1→3)-ß-D-glucan and outdoor temperature.

Conclusions: The results suggest that household waste collectors handling compostable waste can be exposed to airborne (1→3)-ß-D-glucan, especially during the warm season, when more symptoms have been reported among waste collectors, according to previous studies. This cannot be interpreted as a causal relationship as household waste may contain several agents that could cause effects. Further studies are needed to explore such relationships.
DNAssist: the integrated editing and analysis of
molecular biology sequences in Windows
Authors: Patterton Hugh-G. , Graves Steven
Published: July 2002

Motivation: The programs currently available for the analysis of nucleic acid and protein sequences suffer from a variety of problems: Web-based programs often require inconvenient reformatting of sequences when proceeding from one analysis to the next, and commercial-console-based programs are cost prohibitive. Here, we report the development of DNAssist, an inexpensive, multiple-document, interface program for the fully integrated editing and analysis of nucleic acid and protein sequences in the familiar environment of Microsoft Windows.

Availability: DNAssist is available as shareware and may be downloaded from http://www.dnassist.com.

Contact: support@dnassist.com

* To whom correspondence should be addressed: Steven Graves, P.O. Box 1024, Los Alamos, NM 87544, USA, E-mail: steveg@dnassist.com.
Inhibition of p53‐dependent transcription by BOX‐I phospho‐peptide mimetics that bind to p300
Authors: Dornan David , Hupp Ted R
Published: July 2002

The N‐terminal BOX‐I domain of p53 containing a docking site for the negative regulator MDM2 and the positive effector p300, harbours two recently identified phosphorylation sites at Thr18 or Ser20 whose affect on p300 is undefined. Biochemical assays demonstrate that although MDM2 binding is inhibited by these phosphorylations, p300 binding is strikingly stabilized by Thr18 or Ser20 phosphorylation. Introducing EGFP‐BOX‐I domain peptides with an aspartate substitution at Thr18 or Ser20 induced a significant inhibition of endogenous p53‐dependent transcription in cycling cells, in irradiated cells, as well as in cells transiently co‐transfected with p300 and p53. In contrast an EGFP‐wild‐type BOX‐I domain peptide stimulated p53 activity via inhibition of MDM2 protein binding. These results suggest that phosphorylation of p53 at Thr18 or Ser20 can activate p53 by stabilizing the p300–p53 complex and also identify a class of small molecular weight ligands capable of selective discrimination between MDM2‐ and p300‐dependent activities.
Mechanisms of tolerance induction: blockade of co–stimulation
Authors: Sebille Fabien , Vanhove Bernard , Soulillou Jean-Paul
Published: July 2002

Induction of tolerance to transplantation antigens is believed to be a promising way to achieve long–term allograft survival without a deleterious immunosuppressive regimen. T–cell activation, which is an essential feature of graft rejection, requires a first signal provided by T–cell receptor (TCR) ligation and a second signal provided by engagement of co–stimulatory molecules with their respective ligands on antigen–presenting cells. The coordinated triggering of these two independent signalling systems ensures the full T–cell activation, including proliferation and acquisition of effector function. TCR occupancy in the absence of co–stimulatory signals leads to a sustained loss of antigen responsiveness called clonal anergy, which could be of major importance in transplantation.In vivo, co–stimulation blockade was indeed shown to allow for long–term allograft survival in several transplantation models. However, the current continuous identification of new co–stimulatory molecules suggests that a functional redundancy of the system exists and that tolerance to transplantation antigens might be achieved more easily through the combined blockade of two or several co–stimulatory signals. In this review, we analyse the biological effects of the disruption of some co–stimulation pathwaysin vitroandin vivoand discuss their potential interest for tolerance induction.
A Comparative Molecular Analysis of Developing Mouse Forelimbs and Hindlimbs Using Serial Analysis of Gene Expression (SAGE)
Authors: Margulies Elliott H. , Kardia Sharon L.R. , Innis Jeffrey W.
Published: July 2002

The analysis of differentially expressed genes is a powerful approach to elucidate the genetic mechanisms underlying the morphological and evolutionary diversity among serially homologous structures, both within the same organism (e.g., hand vs. foot) and between different species (e.g., hand vs. wing). In the developing embryo, limb-specific expression of Pitx1, Tbx4, andTbx5 regulates the determination of limb identity. However, numerous lines of evidence, including the fact that these three genes encode transcription factors, indicate that additional genes are involved in the Pitx1-Tbx hierarchy. To examine the molecular distinctions coded for by these factors, and to identify novel genes involved in the determination of limb identity, we have used Serial Analysis of Gene Expression (SAGE) to generate comprehensive gene expression profiles from intact, developing mouse forelimbs and hindlimbs. To minimize the extraction of erroneous SAGE tags from low-quality sequence data, we used a new algorithm to extract tags from phred-analyzed sequence data and obtained 68,406 and 68,450 SAGE tags from forelimb and hindlimb SAGE libraries, respectively. We also developed an improved method for determining the identity of SAGE tags that increases the specificity of and provides additional information about the confidence of the tag-UniGene cluster match. The most differentially expressed gene between our SAGE libraries was Pitx1. The differential expression ofTbx4, Tbx5, and several limb-specific Hoxgenes was also detected; however, their abundances in the SAGE libraries were low. Because numerous other tags were differentially expressed at this low level, we performed a ‘virtual‘ subtraction with 362,344 tags from six additional nonlimb SAGE libraries to further refine this set of candidate genes. This subtraction reduced the number of candidate genes by 74%, yet preserved the previously identified regulators of limb identity. This study presents the gene expression complexity of the developing limb and identifies candidate genes involved in the regulation of limb identity. We propose that our computational tools and the overall strategy used here are broadly applicable to other SAGE-based studies in a variety of organisms.

[SAGE data are all available at GEO (http://www.ncbi.nlm.nih.gov/geo/) under accession nos. GSM55 and GSM56, which correspond to the forelimb and hindlimb raw SAGE data.]
Verification of IMRT dose distributions using a water beam imaging system
Authors: Li J. S. , Boyer Arthur L. , Ma C.‐M.
Published: July 2002

A water beam imaging system (WBIS) has been developed and used to verify dose distributions for intensity modulated radiotherapy using dynamic multileaf collimator. This system consisted of a water container, a scintillator screen, a charge‐coupled device camera, and a portable personal computer. The scintillation image was captured by the camera. The pixel value in this image indicated the dose value in the scintillation screen. Images of radiation fields of known spatial distributions were used to calibrate the device. The verification was performed by comparing the image acquired from the measurement with a dose distribution from the IMRT plan. Because of light scattering in the scintillator screen, the image was blurred. A correction for this was developed by recognizing that the blur function could be fitted to a multiple Gaussian. The blur function was computed using the measured image of a 10 cm×10 cm x‐ray beam and the result of the dose distribution calculated using the Monte Carlo method. Based on the blur function derived using this method, an iterative reconstruction algorithm was applied to recover the dose distribution for an IMRT plan from the measured WBIS image. The reconstructed dose distribution was compared with Monte Carlo simulation result. Reasonable agreement was obtained from the comparison. The proposed approach makes it possible to carry out a real‐time comparison of the dose distribution in a transverse plane between the measurement and the reference when we do an IMRT dose verification.
Calculated dosimetric parameters of the IoGold 125I source model 3631‐A
Authors: Wierzbicki Jacek G. , Rivard Mark J. , Waid David S. , Arterbery Vivian Elayne
Published: July 2002

Basic dosimetric parameters as recommended by the AAPM Task Group No. 43 (TG‐43) have been determined for recently available IoGold brachytherapy seeds. Monte Carlo methods (MCNP) were used in the calculation of these parameters in water, and results compared with soon to be published experimental parameters also for IoGold seeds as well with parameters for model 6702 and 6711 seeds. These parameters were the radial dose function, anisotropy factor and constant, and the dose rate constant. Using MCNP, values for the radial dose function at 0.5, 2.0, and 5.0 cm were 1.053, 0.877, and 0.443, respectively. The anisotropy factor was 0.975, 0.946, 0.945, and 0.952 at 0.5, 1.0, 2.0, and 5.0 cm, respectively, with an anisotropy constant of 0.95. The IoGold dose rate constant was determined by excluding the low energy titanium characteristic x rays produced in the IoGold titanium capsule. Using this post TG‐43 revised NIST air kerma methodology, the IoGold dose rate constant was 0.96 cGy h−1 U−1. These calculatively determined parameters for IoGold seeds were compared with those determined experimentally for IoGold seeds, and also compared with parameters determined for model 6702 and 6711 seeds as presented in TG‐43.
Experimental measurements of dosimetric parameters on the transverse axis of a new source
Authors: Li Zuofeng , Fan J. J. , Palta Jatinder R.
Published: July 2002

Permanent prostate implant using or sources is a common treatment choice in the management of early prostate cancer. As sources of new designs are developed and marketed for application in permanent prostate implants, it is of paramount importance that their dosimetric characteristics are carefully determined, in order to maintain a high accuracy of patient treatment. This report presents the results of experimental measurements of the dosimetric parameters performed for a newly available seed source, the model MED3631‐A/M source (IoGold™), manufactured by North American Scientific, Inc. The measurements were performed in a large scanning water phantom, using a diode detector. The positioning of the source and the diode detector was achieved by a computer‐controlled positioning mechanism in the scanning water phantom. The dose rate constant in water for the new source was measured in comparison with an existing source of similar design and verified using thermoluminescent dosimetry (TLD) measurement. The radial dose function values for the source were measured using the diode detector. The measurement technique and the results are compared with the dose distribution parameters for the sources discussed in the AAPM TG43 report and elsewhere [Med. Phys. 26, 570–573 (1999)]. For the dose rate constant in water of the new source, it is recommended that a value of 0.950 cGy/U‐hr be used based on the NIST 1985 air‐kerma strength calibration standard, or 1.060 cGy/U‐hr based on the 1999 NIST air‐kerma strength standard. The measured radial dose function values for the MED3631‐A/M source agree closely with those of the model 6702 source. It is therefore recommended that the radial dose function values for the model 6702 source, as recommended by the AAPM TG43 report, be adopted for the new source as well.
Light bending and perihelion precession: A unified approach
Authors: Brill Dieter R. , Goel Deepak
Published: July 2002

The standard General Relativity results for precession of particle orbits and for bending of null rays are derived as special cases of perturbation of a quantity that is conserved in Newtonian physics, the Runge–Lenz vector. First, this method is applied to give a derivation of these General Relativity effects for the case of the spherically symmetric Schwarzschild geometry. Then the lowest order correction due to an angular momentum of the central body is considered. The results obtained are well known, but the method used is rather more efficient than that found in the standard texts, and it provides a good occasion to use the Runge–Lenz vector beyond its standard applications in Newtonian physics.
Cross-spectral methods for processing speech
Authors: Nelson Douglas J.
Published: July 2002

We present time-frequency methods which are well suited to the analysis of nonstationary multicomponent FM signals, such as speech. These methods are based on group delay, instantaneous frequency, and higher-order phase derivative surfaces computed from the short time Fourier transform (STFT). Unlike more conventional approaches, these methods do not assume a locally stationary approximation of the signal model. We describe the computation of the phase derivatives, the physical interpretation of these derivatives, and a re-mapping algorithm based on these phase derivatives. We show analytically, and by example, the convergence of the re-mapping to the FM representation of the signal. The methods are applied to speech to estimate signal parameters, such as the group delay of a transmission channel and speech formant frequencies. Our goal is to develop a unified method which can accurately estimate speech components in both time and frequency and to apply these methods to the estimation of instantaneous formant frequencies, effective excitation time, vocal tract group delay, and channel group delay. The proposed method has several interesting properties, the most important of which is the ability to simultaneously resolve all FM components of a multicomponent signal, as long as the STFT of the composite signal satisfies a simple separability condition. The method can provide super-resolution in both time and frequency in the sense that it can simultaneously provide time and frequency estimates of FM components, which have much better accuracy than the Heisenberg uncertainty of the STFT. Super-resolution provides the capability to accurately “re-map” each component of the STFT surface to the time and frequency of the FM signal component it represents. To attain high resolution and accuracy, the signal must be jointly estimated simultaneously in time and frequency. This is accomplished by estimating two surfaces, which are essentially the derivatives of the STFT phase with respect to time and frequency. To avoid phase ambiguities, the differentiation is performed as a cross-spectral product.
Study of a novel range-dependent propagation effect with application to the axial injection of signals from the Kaneohe source
Authors: Tappert Frederick D. , Spiesberger John L. , Wolfson Michael A.
Published: July 2002

A novel range-dependent propagation effect occurs when a source is placed on the seafloor in shallow water with a downward refracting sound speed profile, and sound waves propagate down a slope into deep water. Under these conditions, small grazing-angle sound waves slide along the bottom downward and outward from the source until they reach the depth of the sound channel axis in deep water, where they are detached from the sloping bottom and continue to propagate outward near the sound channel axis. This “mudslide” effect is one of a few robust and predictable acoustic propagation effects that occur in range-dependent ocean environments. As a consequence of this effect, a bottom mounted source in shallow water can inject a significant amount of acoustic energy into the axis of the deep ocean sound channel that can then propagate to very long ranges. Numerical simulations with a full-wave range-dependent acoustic model show that the Kaneohe experiment had the appropriate source, bathymetry, and sound speed profiles that allows this effect to operate efficiently. This supports the interpretation that some of the near-axial acoustic signals, received near the coast of California from the bottom mounted source located in shallow water in Kaneohe Bay, Oahu, Hawaii, were injected into the sound channel of the deep Pacific Ocean by this mechanism. Numerical simulations suggest that the mudslide effect is robust.
Comparison between subjective and objective measures of active hearing protector and communication headset attenuation
Authors: Zera Jan , Brammer Anthony J. , Pan George J.
Published: July 2002

A masked-threshold and a loudness-balance method have been developed to estimate the attenuation of communication headsets and hearing protectors with built-in active noise reduction (ANR) systems. Both methods are used to estimate the attenuation of the ANR systems and the masked-threshold method is also used to estimate the total attenuation (active plus passive) of the device. The procedures are designed to be used in the presence of environmental noise, and to minimize the noise exposure of subjects during the measurements. For comparison, physical measurements of insertion loss have also been performed using a miniature microphone in the concha. Experiments showed that the masked-threshold method tends to give increased estimates of the attenuation if the noise reduction of the left and right earcup ANR systems differs, as commonly occurs in practice. In contrast, the loudness-balance method reduces the estimates of the active attenuation. Insertion loss measurements may be influenced by the position of the microphone, owing to the spatial variability of the sound field under an earmuff when the ANR system is operating. Differences between physical and subjective measurements of up to 20 dB have been obtained in this study at frequencies of 250 Hz and below for a device in which the sound pressure varied substantially near, and within, the ear canal.
Acoustic modeling of road vehicles for traffic noise prediction: Determination of the sources heights
Authors: Hamet Jean-François , Pallas Marie-Agnès , Gaulin David , Bérengier Michel C.
Published: July 2002

For traffic noise predictions road vehicles can be modeled by point sources. When dealing with the evaluation of noise barrier’s efficiency or of far-field noise, the knowledge of the sources heights is of primary importance. Their determination can be obtained from two different methods. The first one deals with an inverse fitting procedure performed on experimental excess attenuation results between two receivers 7.50 m apart. Knowing the noise frequency spectrum at the reference microphone and the pavement and close ground impedances, it becomes possible to adjust the source height by minimizing the prediction/measurement difference. By this procedure, the equivalent noise source is found very close to the surface. Otherwise, sources heights can be obtained directly using microphone arrays. These measuring techniques are now commonly used to localize sound sources of railway vehicles. Their application to road vehicles appears to be more recent. For the present case dealing with the determination of the source height only, a simple vertical array can be implemented. Preliminary measurements made on a light vehicle confirm that the acoustic radiation due to the various sources (including engine noise) comes practically entirely from the car underbody, i.e., from a zone close to the ground.
An experimental study of the open end correction coefficient for side branches within an acoustic tube
Authors: Dang Jianwu , Shadle Christine H. , Kawanishi Yasuhito , Honda Kiyoshi , Suzuki Hisayoshi
Published: July 2002

The open end correction coefficient (OECC) of acoustic tubes has been widely investigated under a free-field condition. This study examines OECCs in confined regions, such as side branches within the vocal tract. To do this, a number of mechanical acoustic models are used to examine the effects of the angle of the branch axis and the proximity of the walls of the main tract to the open end of the branch. The OECC is estimated by matching both the peaks and troughs (i.e., spectral maxima and minima) of the computed and measured transfer functions for each model. The results indicate that the OECC of a side branch depends on L/D, where L is the cross dimension of the main tract at the branching point, and D is the branch diameter. For side branches connected to the main tract through a narrow neck, the OECC of each end of the neck is determined using the ratio of the radius of the neck to that of the adjacent section. Two empirical equations for evaluating the OECC within a tract are derived from the present study. Finally, the range of appropriate OECC values for estimating an accurate vocal tract transfer function is discussed, based on the results presented here and morphologic measurements reported previously.
High displacement, high force piezoelectric actuator and sensor
Authors: Bishop Richard , Mossi Karla
Published: July 2002

A piezoelectric actuator and sensor which develops unusually high forces and displacements, and which is very rugged and durable, was invented by NASA at the Langley Research Center, Hampton, Virginia. Face International Corporation, under license from NASA Langley, has furthered the development of this actuator/sensor technology, and has successfully brought it to commercial production. Trade-named THUNDER, the device derives its improved performance from two unique features. First, THUNDER is composed of a piezoelectric ceramic core which is enclosed in a sandwich having metal foil faces. The metal faces are bonded with a very strong hot-melt adhesive which enables the actuator, operating as a unimorph, to develop large displacements and support heavy loads without failure. Second, through unique design features, the ceramic core of THUNDER is subjected to thermal expansion during manufacture. The thermal effects place the faces of the ceramic in compression so that it can undergo severe bending without cracking. The combination of the described design features of THUNDER permit its operation as a sensitive motion sensor and voltage generator as well as making it a superior solid state actuator.
Verification of prediction based on randomized tail-corrected cone-tracing and array modeling
Authors: Dalenbäck Bengt-Inge L.
Published: July 2002

A new room acoustics prediction method, randomized tail-corrected cone-tracing (RTC), is described together with sample prediction/measurement comparisons. RTC is the result of ten years of experience using the image source model, ray- and cone-tracing, and combines elements of all three methods. RTC is a robust number-prediction method, including the effects of frequency-dependent diffuse reflection for both early and late reflections, as well as a method that creates echograms suitable for binaural post-processing and auralization. Further, a WIN32 DLL directivity interface (DDI) is described. The interface is general and is capable of arbitrary data-format translation and accurate distance-dependent high-resolution array modeling including beam steering. The array modeling is either made via a generic DDI module or via modules custom designed based on detailed manufacturer array specifications (transducer placement, directivity pattern, aim, weighting filter, and delay). Sample prediction/measurements comparisons are given for DSP-controlled column arrays under free-field conditions, in a large railway station and in a large church. It is demonstrated that the common fixed measurement distance 10-deg full space data is insufficient for modeling arrays both due to the limited angular resolution and because far-field conditions may not be reached until 30 m distance or beyond.
The nonlinear mesoscopic elasticity class of materials
Authors: Johnson Paul A. , Guyer Robert A.
Published: July 2002

It is becoming clear that the elastic properties of rock are shared by numerous other materials (sand, soil, some ceramics, concrete, etc.). These materials have one or more of the following properties in common: strong nonlinearity, hysteresis in stress–strain relation, and discrete memory. Primarily, it is the material’s compliance, the mesoscopic linkages between the rigid components, that give these materials their unusual elastic properties. It can be said that these materials have nonlinear mesoscopic elasticity and encompass a broad class of materials. Materials with nonlinear mesoscopic elasticity stand in contrast to liquids and crystalline solids whose elasticity is due to contributions of atomic level forces, i.e., materials with atomic elasticity. Atomic elastic materials are well described by the traditional (Landau) theory of elasticity; however, mesoscopic elastic materials are not. Mesoscopic materials are well described by the P–M (Preisach–Mayergoyz) model of nonlinear elasticity developed by Guyer and McCall. A sequence of experiments on numerous materials illustrates the evidence of nonlinear mesoscopic elastic behavior. In experimental analysis a surprising discovery was made: damaged atomic elastic materials behave as mesoscopic elastic materials. It is significant that the nonlinear mechanism(s) in mesoscopic elastic materials remains a mystery.
A broadband omnidirectional barrel-stave flextensional transducer
Authors: Jones D. F. , Christopher D. A.
Published: July 2002

The piezoelectric Class III barrel-stave flextensional transducer is an underwater acoustic source that is capable of generating sound over a wide frequency band. This broadband performance is achieved through coupling the fundamental flexural and longitudinal modes of vibration. Near the low frequency flexural resonance, the Class III transducer is small compared to a wavelength, and its radiation is omnidirectional. However, at frequencies in the vicinity of the longitudinal resonance, the radiation is directional. In this article, we show through the use of a finite element model that the Class III transducer can be designed for omnidirectional radiation over the entire band.
Growth of simultaneous masking for fm<fs: Effects of overall frequency and level
Authors: Bacon Sid P. , Boden Larissa N. , Lee Jungmee , Repovsch Jennifer L.
Published: July 2002

Growth-of-masking (GOM) functions were obtained in three groups of normal-hearing subjects using a simultaneous-masking paradigm. In all cases, the signal frequency (fs) was higher than the masker frequency (fm), either by a certain ratio (1.44) or by a certain distance [3 equivalent rectangular bandwidths (ERBs)]. The purpose was to evaluate the effect of overall frequency on the slope of the steep portion of the GOM function, and to evaluate the change in slope that can occur at high levels. Signal frequency ranged from 400 to 5000 Hz, and masker level ranged from 40 to 95 dB SPL. On average, the slope of the steep portion of the GOM function was about 1.4 for signal frequencies from 400 to 750 Hz, and 2.0 for signal frequencies from 1944 to 5000 Hz. This is consistent with the possibility that the cochlea may behave more linearly at the apical (low-frequency) region than at the basal (high-frequency) region. In addition, for signal frequencies at and above 750 Hz, the slope of the masking function changed from a value much greater than 1.0 to a value of 1.0 at high levels. The change in slope was better correlated with signal sensation level (i.e., amount of masking) than with either signal or masker SPL; the lack of a change at the lower signal frequencies may reflect the smaller amounts of masking there. The change to a linear growth of masking may represent a change in the response to the signal from compressive to linear at high levels.