bluuebunny/crossref_metadata_2025 huggingface dataset:
Ligand-insensitive State of Cardiac ATP-sensitive K+ Channels
Authors: Alekseev Alexey E. , Brady Peter A. , Terzic Andre
Published: July 2002

The mechanism by which ATP-sensitive K+ (KATP) channels open in the presence of inhibitory concentrations of ATP remains unknown. Herein, using a four-state kinetic model, we found that the nucleotide diphosphate UDP directed cardiac KATP channels to operate within intraburst transitions. These transitions are not targeted by ATP, nor the structurally unrelated sulfonylurea glyburide, which inhibit channel opening by acting on interburst transitions. Therefore, the channel remained insensitive to ATP and glyburide in the presence of UDP. “Rundown” of channel activity decreased the efficacy with which UDP could direct and maintain the channel to operate within intraburst transitions. Under this condition, the channel was sensitive to inhibition by ATP and glyburide despite the presence of UDP. This behavior of the KATP channel could be accounted for by an allosteric model of ligand-channel interaction. Thus, the response of cardiac KATP channels towards inhibitory ligands is determined by the relative lifetime the channel spends in a ligand-sensitive versus -insensitive state. Interconversion between these two conformational states represents a novel basis for KATP channel opening in the presence of inhibitory concentrations of ATP in a cardiac cell.
Patch Clamp on the Luminal Membrane of Exocrine Gland Acini from Frog Skin (Rana esculenta) Reveals the Presence of Cystic Fibrosis Transmembrane Conductance Regulator–like Cl− Channels Activated by Cyclic AMP
Authors: Sørensen Jakob Balslev , Larsen Erik Hviid
Published: July 2002

Chloride channels in the luminal membrane of exocrine gland acini from frog skin (Rana esculenta) constituted a single homogeneous population. In cell-attached patches, channels activated upon exposure to isoproterenol, forskolin, or dibutyryl-cAMP and isobutyl-1-methyl-xanthine rectified in the outward direction with a conductance of 10.0 ± 0.4 pS for outgoing currents. Channels in stimulated cells reversed at 0 mV applied potential, whereas channels in unstimulated cells reversed at depolarized potentials (28.1 ± 6.7 mV), indicating that Cl− was above electrochemical equilibrium in unstimulated, but not in stimulated, cells. In excised inside-out patches with 25 mM Cl− on the inside, activity of small (8-pS) linear Cl−-selective channels was dependent upon bath ATP (1.5 mM) and increased upon exposure to cAMP-dependent protein kinase. The channels displayed a single substate, located just below 2/3 of the full channel amplitude. Halide selectivity was identified as PBr > PI > PCl from the Goldman equation; however, the conductance sequence when either halide was permeating the channel was GCl > GBr >> GI. In inside-out patches, the channels were blocked reversibly by 5-nitro-2-(3-phenylpropylamino)benzoic acid, glibenclamide, and diphenylamine-2-carboxylic acid, whereas 4,4-diisothiocyanatostilbene-2,2-disulfonic acid blocked channel activity completely and irreversibly. Single-channel kinetics revealed one open state (mean lifetime = 158 ± 72 ms) and two closed states (lifetimes: 12 ± 4 and 224 ± 31 ms, respectively). Power density spectra had a double-Lorentzian form with corner frequencies 0.85 ± 0.11 and 27.9 ± 2.9 Hz, respectively. These channels are considered homologous to the cystic fibrosis transmembrane conductance regulator Cl− channel, which has been localized to the submucosal skin glands in Xenopus by immunohistochemistry (Engelhardt, J.F., S.S. Smith, E. Allen, J.R. Yankaskas, D.C. Dawson, and J.M. Wilson. 1994. Am. J. Physiol. 267: C491–C500) and, when stimulated by cAMP-dependent phosphorylation, are suggested to function in chloride secretion.
Specific and Nonspecific Effects of Protein Kinase C on the Epithelial Na + Channel
Authors: Awayda Mouhamed S.
Published: July 2002

The Xenopus oocyte expression system was used to explore the mechanisms of inhibition of the cloned rat epithelial Na+ channel (rENaC) by PKC (Awayda, M.S., I.I. Ismailov, B.K. Berdiev, C.M. Fuller, and D.J. Benos. 1996. J. Gen. Physiol. 108:49–65) and to determine whether human ENaC exhibits similar regulation. Effects of PKC activation on membrane and/or channel trafficking were determined using impedance analysis as an indirect measure of membrane area. hENaC-expressing oocytes exhibited an appreciable activation by hyperpolarizing voltages. This activation could be fit with a single exponential, described by a time constant (τ) and a magnitude (ΔI V). A similar but smaller magnitude of activation was also observed in oocytes expressing rENaC. This activation likely corresponds to the previously described effect of hyperpolarizing voltage on gating of the native Na+ channel (Palmer, L.G., and G. Frindt. 1996. J. Gen. Physiol. 107:35–45). Stimulation of PKC with 100 nM PMA decreased ΔIV in hENaC-expressing oocytes to a plateau at 57.1 ± 4.9% (n = 6) of baseline values at 20 min. Similar effects were observed in rENaC-expressing oocytes. PMA decreased the amiloride-sensitive hENaC slope conductance (gNa) to 21.7 ± 7.2% (n = 6) of baseline values at 30 min. This decrease was similar to that previously reported for rENaC. This decrease of g Na was attributed to a decrease of membrane capacitance (C m), as well as the specific conductance (gm/Cm ). The effects on gm/Cm reached a plateau within 15 min, at ∼60% of baseline values. This decrease is likely due to the specific ability of PKC to inhibit ENaC. On the other hand, the decrease of Cm was unrelated to ENaC and is likely an effect of PKC on membrane trafficking, as it was observed in ENaC-expressing as well as control oocytes. At lower PMA concentrations (0.5 nM), smaller changes of Cm were observed in rENaC- and hENaC-expressing oocytes, and were preceded by larger changes of gm and by changes of gm/Cm, indicating specific effects on ENaC. These findings indicate that PKC exhibits multiple and specific effects on ENaC, as well as nonspecific effects on membrane trafficking. Moreover, these findings provide the electrophysiological basis for assessing channel-specific effects of PKC in the Xenopus oocyte expression system.
Functional Coupling of the β1 Subunit to the Large Conductance Ca2+-Activated K+ Channel in the Absence of Ca2+
Authors: Nimigean Crina M. , Magleby Karl L.
Published: July 2002

Coexpression of the β1 subunit with the α subunit (mSlo) of BK channels increases the apparent Ca2+ sensitivity of the channel. This study investigates whether the mechanism underlying the increased Ca2+ sensitivity requires Ca2+, by comparing the gating in 0 Ca2+i of BK channels composed of α subunits to those composed of α+β1 subunits. The β1 subunit increased burst duration ∼20-fold and the duration of gaps between bursts ∼3-fold, giving an ∼10-fold increase in open probability (Po) in 0 Ca2+i. The effect of the β1 subunit on increasing burst duration was little changed over a wide range of Po achieved by varying either Ca2+i or depolarization. The effect of the β1 subunit on increasing the durations of the gaps between bursts in 0 Ca2+i was preserved over a range of voltage, but was switched off as Ca2+i was increased into the activation range. The Ca2+-independent, β1 subunit-induced increase in burst duration accounted for 80% of the leftward shift in the Po vs. Ca2+i curve that reflects the increased Ca2+ sensitivity induced by the β1 subunit. The Ca2+-dependent effect of the β1 subunit on the gaps between bursts accounted for the remaining 20% of the leftward shift. Our observation that the major effects of the β1 subunit are independent of Ca2+i suggests that the β1 subunit mainly alters the energy barriers of Ca2+-independent transitions. The changes in gating induced by the β1 subunit differ from those induced by depolarization, as increasing Po by depolarization or by the β1 subunit gave different gating kinetics. The complex gating kinetics for both α and α+β1 channels in 0 Ca2+i arise from transitions among two to three open and three to five closed states and are inconsistent with Monod-Wyman-Changeux type models, which predict gating among only one open and one closed state in 0 Ca2+i.
Extracellular Atp Inhibits the Small-Conductance K Channel on the Apical Membrane of the Cortical Collecting Duct from Mouse Kidney
Authors: Lu Ming , MacGregor Gordon G. , Wang Wenhui , Giebisch Gerhard
Published: July 2002

We have used the patch-clamp technique to study the effects of changing extracellular ATP concentration on the activity of the small-conductance potassium channel (SK) on the apical membrane of the mouse cortical collecting duct. In cell-attached patches, the channel conductance and kinetics were similar to its rat homologue. Addition of ATP to the bathing solution of split-open single cortical collecting ducts inhibited SK activity. The inhibition of the channel by ATP was reversible, concentration dependent (Ki = 64 μM), and could be completely prevented by pretreatment with suramin, a specific purinergic receptor (P2) blocker. Ranking of the inhibitory potency of several nucleotides showed strong inhibition by ATP, UTP, and ATP-γ-S, whereas α, β-Me ATP, and 2-Mes ATP failed to affect channel activity. This nucleotide sensitivity is consistent with P2Y2 purinergic receptors mediating the inhibition of SK by ATP. Single channel analysis further demonstrated that the inhibitory effects of ATP could be elicited through activation of apical receptors. Moreover, the observation that fluoride mimicked the inhibitory action of ATP suggests the activation of G proteins during purinergic receptor stimulation. Channel inhibition by ATP was not affected by blocking phospholipase C and protein kinase C. However, whereas cAMP prevented channel blocking by ATP, blocking protein kinase A failed to abolish the inhibitory effects of ATP. The reduction of K channel activity by ATP could be prevented by okadaic acid, an inhibitor of protein phosphatases, and KT5823, an agent that blocks protein kinase G. Moreover, the effect of ATP was mimicked by cGMP and blocked by L-NAME (NG-nitro-l-arginine methyl ester). We conclude that the inhibitory effect of ATP on the apical K channel is mediated by stimulation of P2Y2 receptors and results from increasing dephosphorylation by enhancing PKG-sensitive phosphatase activity.
𝛽-expansions with deleted digits for Pisot numbers 𝛽
Authors: Lalley Steven
Published: July 2002

An algorithm is given for computing the Hausdorff dimension of the set(s)

Λ
=
Λ
(
β
,
D
)

\Lambda =\Lambda (\beta ,D)

of real numbers with representations

x
=

∑

n
=
1

∞

d
n

β

−
n

x=\sum _{n=1}^\infty d_n \beta ^{-n}

, where each

d
n

∈
D

d_n \in D

, a finite set of “digits”, and

β
>
0

\beta >0

is a Pisot number. The Hausdorff dimension is shown to be

log
⁡
λ

/

log
⁡
β

\log \lambda /\log \beta

, where

λ
\lambda

is the top eigenvalue of a finite 0-1 matrix

A
A

, and a simple algorithm for generating

A
A

from the data

β
,
D

\beta ,D

is given.
A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms I
Authors: Kaloshin Vadim , Hunt Brian
Published: July 2002

For diffeomorphisms of smooth compact manifolds, we consider the problem of how fast the number of periodic points with period

n
n

grows as a function of

n
n

. In many familiar cases (e.g., Anosov systems) the growth is exponential, but arbitrarily fast growth is possible; in fact, the first author has shown that arbitrarily fast growth is topologically (Baire) generic for

C
2

C^2

or smoother diffeomorphisms. In the present work we show that, by contrast, for a measure-theoretic notion of genericity we call “prevalence”, the growth is not much faster than exponential. Specifically, we show that for each

δ
>
0

\delta > 0

, there is a prevalent set of (

C

1
+
ρ

C^{1+\rho }

or smoother) diffeomorphisms for which the number of period

n
n

points is bounded above by

exp
⁡
(
C

n

1
+
δ

)

\operatorname {exp}(C n^{1+\delta })

for some

C
C

independent of

n
n

. We also obtain a related bound on the decay of the hyperbolicity of the periodic points as a function of

n
n

. The contrast between topologically generic and measure-theoretically generic behavior for the growth of the number of periodic points and the decay of their hyperbolicity shows this to be a subtle and complex phenomenon, reminiscent of KAM theory.
Antigen-stimulated Activation of Phospholipase D1b by Rac1, ARF6, and PKCα in RBL-2H3 Cells
Authors: Powner Dale J. , Hodgkin Matthew N. , Wakelam Michael J.O.
Published: July 2002

Phospholipase D (PLD) activity can be detected in response to many agonists in most cell types; however, the pathway from receptor occupation to enzyme activation remains unclear. In vitro PLD1b activity is phosphatidylinositol 4,5-bisphosphate dependent via an N-terminal PH domain and is stimulated by Rho, ARF, and PKC family proteins, combinations of which cooperatively increase this activity. Here we provide the first evidence for the in vivo regulation of PLD1b at the molecular level. Antigen stimulation of RBL-2H3 cells induces the colocalization of PLD1b with Rac1, ARF6, and PKCα at the plasma membrane in actin-rich structures, simultaneously with cooperatively increasing PLD activity. Activation is both specific and direct because dominant negative mutants of Rac1 and ARF6 inhibit stimulated PLD activity, and surface plasmon resonance reveals that the regulatory proteins bind directly and independently to PLD1b. This also indicates that PLD1b can concurrently interact with a member from each regulator family. Our results show that in contrast to PLD1b's translocation to the plasma membrane, PLD activation is phosphatidylinositol 3-kinase dependent. Therefore, because inactive, dominant negative GTPases do not activate PLD1b, we propose that activation results from phosphatidylinositol 3-kinase–dependent stimulation of Rac1, ARF6, and PKCα.
Design and implementation of a qualitative simulation model of lambda phage infection.
Authors: Heidtke K R , Schulze-Kremer S
Published: July 2002

MOTIVATION: Molecular biology databases hold a large number of empirical facts about many different aspects of biological entities. That data is static in the sense that one cannot ask a database 'What effect has protein A on gene B?' or 'Do gene A and gene B interact, and if so, how?'. Those questions require an explicit model of the target organism. Traditionally, biochemical systems are modelled using kinetics and differential equations in a quantitative simulator. For many biological processes however, detailed quantitative information is not available, only qualitative or fuzzy statements about the nature of interactions. RESULTS: We designed and implemented a qualitative simulation model of lambda phage growth control in Escherichia coli based on the existing simulation environment QSim. Qualitative reasoning can serve as the basis for automatic transformation of contents of genomic databases into interactive modelling systems that can reason about the relations and interactions of biological entities.
Remembering Robert Sobel (1931–1999)
Authors: Sicilia David B.
Published: July 2002

Longstanding debates among academic historians about the role of the
narrative and the need (or not) for
relevance are not likely to end any time
soon. Business historians have been relatively unreflective about such
matters, at least compared with, say, labor or women’s historians, who
regularly sprinkle their journals with historiographic reassessments.
Perhaps this is because there was little on the theoretical end of the scale
in business history to sustain earnest debate prior to the publication of
Alfred Chandler’s first masterwork, Strategy and
Structure, scarcely more than a generation ago. Still, it
was Allan Nevins—the journalist cum Columbia
University history professor whose prodigious writings included several
elegant business biographies—who memorably satirized the history academy
with “Dr. Dry-as-Dust,” a crusty purveyor of densely ponderous prose for
like-minded scholarly elites.
Markets, Networks, and the Rise of Chrysler in Old Detroit, 1920–1940
Authors: Schwartz Michael
Published: July 2002

During the two decades before World War II, as this article demonstrates, the relationship between the Big Three American automakers and their parts suppliers was remarkably similar to the celebrated cooperation of Japanese auto assemblers and their trading partners after 1980. Unlike the arms-length multisourcing that characterized American firms after 1960, the prewar Detroit production culture featured collaborative development, cost sharing, and long-term innovative relationships. This system nurtured the rise of Chrysler, which not only grew from a standing start in 1920 to convert the General Motors-Ford duopoly into the “Big Three” by 1930, but also established itself as the industry's leader in innovation and profitability.
Mavericks and Mavens of Business History: Miriam Beard and Henrietta Larson
Authors: Yeager Mary A.
Published: July 2002

This is the story of two women with differing visions about business who have largely been forgotten. Miriam Beard, the maverick daughter of Progressive reformers Charles and Mary Beard, wrote the first international cultural history of the businessman in 1938. Henrietta M. Larson was Harvard Business School's first lady, the first female faculty member and the first woman to be tenured there. The two women never met or interacted. Yet their lives and histories were entangled when one woman, Henrietta, wrote a critical review about the contributions of the other. This article uses their untold story to trace the contentious process of professionalization that sidelined one maverick outsider and kept a maven insider on the margins of a fledgling discipline she had helped to create. Its significance is to make gender central to the reintegration of business and culture and of women's roles in the historiography of business.
Chaotic behaviour of the Rikitake dynamo with symmetric mechanical friction and azimuthal currents
Authors: Plunian F. , Marty Ph. , Alemany A.
Published: July 2002

We propose a new description of the two–disc dynamo, considering azimuthal currents in the rotating discs, as proposed by H. K. Moffatt for the one–disc dynamo, in addition to symmetric mechanical friction applied to the discs, whose neglect constitutes a fundamental error, as shown by R. Hide. The linear stability of the steady state is analysed and it is shown that the system presents chaotic reversals, depending on the parameters of the problem.
Growth and patterning in the conodont skeleton
Authors: Donoghue Philip C. J.
Published: July 2002

Recent advances in our understanding of conodont palaeobiology and functional morphology have rendered established hypotheses of element growth untenable. In order to address this problem, hard tissue histology is reviewed paying particular attention to the relationships during growth of the component hard tissues comprising conodont elements, and ignoringa prioriassumptions of the homologies of these tissues. Conodont element growth is considered further in terms of the pattern of formation, of which four distinct types are described, all possibly derived from a primitive condition after heterochronic changes in the timing of various developmental stages. It is hoped that this may provide further means of unravelling conodont phylogeny. The manner in which the tissues grew is considered homologous with other vertebrate hard tissues, and the elements appear to have grown in a way similar to the growing scales and growing dentition of other vertebrates.
Growth control mechanisms in normal and transformed intestinal cells
Authors: Burgess Antony W.
Published: July 2002

The cells populating the intestinal crypts are part of a dynamic tissue system which involves the self–renewal of stem cells, a commitment to proliferation, lineage–specific differentiation, movement and cell death. Our knowledge of these processes is limited, but even now there are important clues to the nature of the regulatory systems, and these clues are leading to a better understanding of intestinal cancers. Few intestinal–specific markers have been described; however, homeobox genes such ascdx–2appear to be important for morphogenic events in the intestine. There are several intestinal cell surface proteins such as the A33 antigen which have been used as targets for immunotherapy. Many regulatory cytokines (lymphokines or growth factors) influence intestinal development: enteroglucagon, IL–2, FGF, EGF family members. In conjunction with cell–cell contact and/or ECM, these cytokines lead to specific differentiation signals. Although the tissue distribution of mitogens such as EGF, TGFα, amphiregulin, betacellulin, HB–EGF and cripto have been studied in detail, the physiological roles of these proteins have been difficult to determine. Clearly, these mitogens and the corresponding receptors are involved in the maintenance and progression of the tumorigenic state. The interactions between mitogenic, tumour suppressor and oncogenic systems are complex, but the tumorigenic effects of multiple lesions in intestinal carcinomas involve synergistic actions from lesions in these different systems. Together, the truncation ofapcand activation of therasoncogene are sufficient to induce colon tumorigenesis. If we are to improve cancer therapy, it is imperative that we discover the biological significance of these interactions, in particular the effects on cell division, movement and survival.
The evolution of avian parental care
Authors: Burley N. T. , Johnson K.
Published: July 2002

A stage model traces key behavioural tactics and life–history traits that are involved in the transition from promiscuity with no parental care, the mating system that typifies reptiles, to that typical of most birds, social monogamy with biparental care. In stage I, females assumed increasing parental investment in precocial young, female choice of mates increased, female–biased mating dispersal evolved and population sex ratios became male biased. In stage II, consortships between mating partners allowed males to attract rare social mates, provided a mechanism for paternity assessment and increased female ability to assess mate quality. In stage III, relative female scarcity enabled females to demand parental investment contributions from males having some paternity certainty. This innovation was facilitated by the nature of avian parental care; i.e. most care–giving activities can be adopted in small units. Moreover, the initial cost of care giving to males was small compared with its benefit to females. Males, however, tended to decline to assume non–partitionable, risky, or relatively costly parental activities. In stage IV, altriciality coevolved with increasing biparental care, resulting in social monogamy. Approaches for testing behavioural hypotheses are suggested.
Specific tracheal migration is mediated by complementary expression of cell surface proteins
Authors: Boube Muriel , Martin-Bermudo Maria D. , Brown Nicholas H. , Casanova Jordi
Published: July 2002

Migration of the Drosophila tracheal cells relies on cues provided by nearby cells; however, little is known about how these signals specify a migratory path. Here we investigate the role of cell surface proteins in the definition of such a pathway. We have found that the PS1 integrin is required in the tracheal cells of the visceral branch, whereas the PS2 integrin is required in the visceral mesoderm; both integrins are necessary for the spreading of the visceral branch over its substratum. This is the first identification of a cell surface molecule with expression restricted to a subset of tracheal cells that all migrate in a given direction. We have also found that expression of PS1 in the visceral branch is regulated by the genes that direct tracheal cell migration, showing that integrin expression is part of the cell-fate program that they specify. These results support a model in which signal transduction determines the tracheal migratory pathways by regulating the expression of cell surface proteins, which in turn interact with surface molecules on the surrounding cell population.
Identification of the Modifier ofMin2 (Mom2) Locus, a New Mutation That InfluencesApc-Induced Intestinal Neoplasia
Authors: Silverman Karen A. , Koratkar Revati , Siracusa Linda D. , Buchberg Arthur M.
Published: July 2002

Min(Multipleintestinalneoplasia) mice carry a dominant mutation in the adenomatous polyposis coli (Apc) gene and develop multiple adenomas throughout their intestinal tract (Moser et al. 1990; Su et al. 1992). Polyp multiplicity inMinmice is greatly influenced by genetic background. A modifier locus,Mom1(ModifierofMin1), was identified and localized to distal mouse chromosome 4 (Moser et al. 1992; Dietrich et al. 1993), and accounts for some of the genetic variance in polyp multiplicity.Mom1is a semidominant modifier of polyp size and multiplicity inMinmice (Gould and Dove 1997), and encodes the secretory type II nonpancreatic phospholipase A2(Pla2g2a) gene (MacPhee et al. 1995; Cormier et al. 1997, 2000). We now report the identification of a secondModifierofMin2 (Mom2) locus that is the result of a spontaneous mutation. One resistantMom2allele can suppress 88%–95% of polyps detected inApcMin/+ mice, indicating thatMom2acts in a dominant fashion. Linkage analysis has localizedMom2to distal mouse chromosome 18. The effects of theMom2locus on reducing polyp multiplicity are stronger than the effects of theMom1locus, in both the small and large intestines. SomeApcMin/+ mice that carried one resistantMom2allele were tumor-free at 21 weeks of age, even in the absence of a resistantMom1allele. Thus, the resistantMom2allele can, in some cases, completely suppress the penetrance of theApcMinmutation.
Annotated Expressed Sequence Tags and cDNA Microarrays for Studies of Brain and Behavior in the Honey Bee
Authors: Whitfield Charles W. , Band Mark R. , Bonaldo Maria F. , Kumar Charu G. , Liu Lei , Pardinas Jose R. , Robertson Hugh M. , Soares M. Bento , Robinson Gene E.
Published: July 2002

To accelerate the molecular analysis of behavior in the honey bee (Apis mellifera), we created expressed sequence tag (EST) and cDNA microarray resources for the bee brain. Over 20,000 cDNA clones were partially sequenced from a normalized (and subsequently subtracted) library generated from adultA. melliferabrains. These sequences were processed to identify 15,311 high-quality ESTs representing 8912 putative transcripts. Putative transcripts were functionally annotated (using the Gene Ontology classification system) based on matching gene sequences inDrosophila melanogaster. The brain ESTs represent a broad range of molecular functions and biological processes, with neurobiological classifications particularly well represented. Roughly half ofDrosophilagenes currently implicated in synaptic transmission and/or behavior are represented in theApisEST set. OfApissequences with open reading frames of at least 450 bp, 24% are highly diverged with no matches to known protein sequences. Additionally, over 100Apistranscript sequences conserved with other organisms appear to have been lost from theDrosophilagenome. DNA microarrays were fabricated with over 7000 EST cDNA clones putatively representing different transcripts. Using probe derived from single bee brain mRNA, microarrays detected gene expression for 90% ofApiscDNAs two standard deviations greater than exogenous control cDNAs.

[The sequence data described in this paper have been submitted to Genbank data library under accession nos.BI502708–BI517278. The sequences are also available athttp://titan.biotec.uiuc.edu/bee/honeybee_project.htm.]
Dynamic wedge versus physical wedge: A Monte Carlo study
Authors: Shih Rompin , Li X. Allen , Chu James C. H.
Published: July 2002

The purpose of this study is to analyze the characteristics of dynamic wedges (DW) and to compare DW to physical wedges (PW) in terms of their differences in affecting beam spectra, energy fluence, angular distribution, contaminated electrons, and dose distributions. The EGS4/BEAM Monte Carlo codes were used to simulate the exact geometry of a 6 MV beam and to calculate 3‐D dose distributions in phantom. The DW was simulated in accordance with the segmented treatment tables (STT). The percentage depth dose curves and beam profiles for PW, DW, and open fields were measured and used to verify the Monte Carlo simulations. The Monte Carlo results were found to agree within 2% with the measurements performed using film and ionizing chambers in a water phantom. The present EGS4 calculation reveals that the effects of a DW on beam spectral and angular distributions, as well as electron contamination, are much less significant than those for a PW. For the 6 MV photon beam, a 45° PW can result in a 30% increase in mean photon energy due to the effect of beam hardening. It can also introduce a 5% dose reduction in the build‐up region due to the reduction of contaminated electrons by the PW. Neither this mean‐energy increase nor such dose reduction is found for a DW. Compared to a DW, a PW alters the photon‐beam spectrum significantly. The dosimetric differences between a DW and a PW are significant and clearly affect the clinical use of these beams. The data presented may be useful for DW commissioning.
Computerized classification of suspicious regions in chest radiographs using subregion Hotelling observers
Authors: Baydush Alan H. , Catarious David M. , Lo Joseph Y. , Abbey Craig. K. , Floyd Carey E.
Published: July 2002

We propose to investigate the use of subregion Hotelling observers (SRHOs) in conjunction with perceptrons for the computerized classification of suspicious regions in chest radiographs for being nodules requiring follow up. Previously, 239 regions of interest (ROIs), each containing a suspicious lesion with proven classification, were collected. We chose to investigate the use of SRHOs as part of a multilayer classifier to determine the presence of a nodule. Each SRHO incorporates information about signal, background, and noise correlation for classification. For this study, 225 separate Hotelling observers were set up in a grid across each ROI. Each separate observer discriminates an 8 by 8 pixel area. A round robin sampling scheme was used to generate the 225 features, where each feature is the output of the individual observers. These features were then rank ordered by the magnitude of the weights of a perceptron. Once rank ordered, subsets of increasing number of features were selected to be used in another perceptron. This perceptron was trained to minimize mean squared error and the output was a continuous variable representing the likelihood of the region being a nodule. Performance was evaluated by receiver operating characteristic (ROC) analysis and reported as the area under the curve The classifier was optimized by adding additional features until the declined. The optimized subset of observers then were combined using a third perceptron. A subset of 80 features was selected which gave an of 0.972. Additionally, at 98.6% sensitivity, the classifier had a specificity of 71.3% and increased the positive predictive value from 60.7% to 84.1%. Preliminary results suggest that using SRHOs in combination with perceptrons can provide a successful classification scheme for pulmonary nodules. This approach could be incorporated into a larger computer aided detection system for decreasing false positives.
Mathematical morphology in computerized analysis of angiograms in age‐related macular degeneration
Authors: Barthes Angela , Conrath John , Rasigni Monique , Adel Mouloud , Petrakian Jean‐Pierre
Published: July 2002

This paper deals with image processing of numerical retinal angiograms in order to facilitate diagnosis and follow‐up in age‐related macular degeneration (AMD) which is currently the main cause of blindness in industrialized countries. A computerized scheme using principally mathematical morphology operators is proposed for detecting and counting drusen, which are precursor lesions of the ocular fundus. In order to check the feasibility of this approach, results relative to 58 retinal images are compared with those given by three retinal specialists independently. From manual counting measures it is found that interobserver correlation coefficients lie in the range 0.71–0.78. On the other hand, a correlation coefficient of 0.89 is obtained when the average of the three expert countings is compared with the drusen number given by the computerized method. This coefficient is improved from 0.89 to 0.93 by processing only frames captured immediately after the appearance of a dye consecutive to intraveinous sodium fluorescein injection. Compared to the manual analysis which is, among other things, tedious and time consuming, the computerized analysis is both quicker and more objective. Validation by the practitioner is however necessary, given possible detection errors. The proposed computerized scheme for detecting and counting drusen may be easily automated and so should prove useful in clinical studies which involve high volume analysis of retinal angiograms.
Polarized x rays for the in vivo measurements of heavy metals
Authors: Kiliç Ayhan
Published: July 2002

A Monte Carlo model has been developed, using the EGS4 code, to aid the design and optimization of a polarized source for in vivo x‐ray fluorescence (XRF) analysis of platinum (Pt). The modeled code is based on a 300 kV clinical x‐ray therapy unit at Singleton Hospital. The code handles five individual components (x‐ray tube, filter, polarizer, sample, and detector) which the user assembles as needed, thus allowing the facility for simulation of a wide variety of XRF systems. For each component, all the physical dimensions and materials involved are set by the user. The model includes polarized photon transport modification, K‐edge fluorescent photon transport modification and K‐edge sampling method for mixtures (a facility previously available only for simple compounds). It incorporates a variance reduction technique (forcing photon interaction) and uses random number generator called RANMAR. Also EGS4PICT (The EGS4 Shower Display System for PC) is built in to display a shower picture at every stage of simulation. The selected polarizer materials tested are C, Al, Fe, Cu, Sn, and Pb. The material shape and thickness are investigated. The secondary beam collimator diameter, length, and material are also studied. Results are compared with analytical models and experiment.
Scintillating fiber optic screens: A comparison of MTF, light conversion efficiency, and emission angle with Gd2O2S:Tb screens
Authors: Yu Tong , Sabol John M. , Seibert J. Anthony , Boone John M.
Published: July 2002

The widespread effort in developing digital imaging systems has led to large area high pixel density photodetectors such as charge coupled devices (CCDs), amorphous silicon photodiode arrays, and complementary metal oxide semiconductor (CMOS) imagers. These photodetectors have different capabilities, characteristics, and requirements than conventional silver‐halide‐based film, and this fact has led to a new generation of exotic scintillators, including fiber optic screens made from scintillating glass. The scintillator performance characteristics of five different scintillating fiber optic screens and two conventional Gd2O2S:Tb screens (one 34 mg/cm2 and the other 60 mg/cm2) were measured and compared. The measurements that were made included the angular dependence of light emission relative to the normal, the modulation transfer function (MTF), and the absolute effective conversion efficiency (light photons per absorbed x‐ray photon). It was found that the light emission of scintillating fiber optic screens is markedly forward peaked (depending on the sample) compared to conventional screens or Lambertian emitters. The MTFs of the five scintillating fiber optic screens measured were comparable and fell approximately midway between the two conventional screen MTFs. One of the scintillating fiber optic screens demonstrated light efficiency similar to the thick (60 mg/cm2) conventional screen, another had light output capabilities similar to the thin (34 mg/cm2) conventional screen, and the three others were less efficient than the thin screen. The non‐Lambertian characteristics of the fiber optic scintillators will cause errors of up to 75% in lens efficiency calculations if a Lambertian source is assumed. The conventional screens were found to conform within about 5% of an ideal Lambertian emitter.
Evaluation of imaging geometries calculated from biplane images
Authors: Esthappan Jacqueline , Harauchi Hajime , Hoffmann Kenneth R.
Published: July 2002

A technique is developed that will calculate accurate and reliable imaging geometries and three‐dimensional (3D) positions from biplane images of a calibration phantom. The calculated data provided by our technique will facilitate accurate 3D analysis in various clinical applications. Biplane images of a Lucite cube containing lead beads 1 mm in diameter were acquired. After identifying corresponding beads in both images and calculating their image positions, the 3D positions of the beads relative to each focal spot were determined. From these data, the transformation relating the 3D configurations were calculated to give the imaging geometry relating the biplane views. The 3D positions of objects were determined from the biplane images along with the corresponding imaging geometries. In addition, methods are developed to evaluate the quality of the calculated results on a case‐by‐case basis in the clinical setting. Methods are presented for evaluating the reproducibility of the calculated geometries and 3D positions, the accuracy of calculated object sizes, and the effects of errors due to time jitter, variation in user‐indication, centering, and distortions on the calculated geometries and 3D reconstructions. The precision of the translation vectors and rotation matrices of the calculated geometries were within 1% and 1°, respectively, in phantom studies, with estimated accuracies of approximately 0.5% and 0.4°, respectively, in simulation studies. The precisions of the absolute 3D positions and orientations of the calculated 3D reconstructions were approximately 2 mm and 0.5°, respectively, in phantom studies, with estimated accuracies of approximately 1.5 mm and 0.4°, respectively, in simulation studies. This technique will provide accurate and precise imaging geometries as well as 3D positions from biplane images, thereby facilitating 3D analysis in various clinical applications. We believe that the study presented here is unique in that it represents the first steps toward understanding and evaluating the reliability of these 3D calculations in the clinical situation.
Further improvements in dose distributions are unlikely to affect cure rates
Authors: Schulz R. J.
Published: July 2002

The development of computers and computer‐controlled devices has, on the whole, had a profound impact on how things are accomplished in our industrialized society, and this is true for radiation therapy as well. In most issues of Medical Physics there are papers describing how computer‐controlled accelerators and multi‐leaf collimators used in combination with advanced treatment‐planning systems, which in turn require multiple CT or MRI scans, can produce more uniform and precisely defined dose distributions limited to the treatment volume, and thereby permit larger tumor doses. The inherent assumption underlying this so‐called Conformal Therapy is that its introduction will result in higher cure rates; however, there is scant evidence to support this assumption, and it is possible that the reverse may be true. It is recommended that randomized/prospective trials of this new technology be undertaken before it becomes so widespread that such an evaluation is no longer possible.
Preprocessing of control portal images for patient setup verification during the treatments in external radiotherapy
Authors: Hilt Gisèle , Wolf Didier , Aletti Pierre
Published: July 2002

The main problem in processing the control portal images is their poor quality. We have developed a way of improving the image quality to allow a segmentation stage. Three items were studied for this purpose the background gradient of intensity correction, the noise reduction, and the image restoration. The background was corrected by subtracting a smoothed version of the image from the original. We tested 15 noise reduction methods. The most appropriate for control portal images was found to be the truncated average. Finally, four restoration techniques were compared. The maximum a posteriori (MAP) algorithm was the most efficient. The algorithms were tested over a wide range of conditions (image quality). They produced a great improvement in anatomic detail for all the imaging systems, energies, and anatomical zones tested. For example, the signal‐to‐noise ratio of a SRI‐100 pelvis image, acquired with 4 monitor units (MU) at 10 MV (very low quality image), increased from 0.97 to 42.84 after preprocessing. We found that the improvement in image quality facilitated or even enabled segmentation of the control portal images. The percentage of segments belonging to a structure increased from 30% to 65% in the example cited. The preprocessing of control portal images is the first step in checking the patient setup.
Saturation current and collection efficiency for ionization chambers in pulsed beams
Authors: DeBlois François , Zankowski Corey , Podgorsak Ervin B.
Published: July 2002

Saturation currents and collection efficiencies in ionization chambers exposed to pulsed megavoltage photon and electron beams are determined assuming a linear relationship between and in the extreme near‐saturation region, with I and the chamber current and polarizing voltage, respectively. Careful measurements of chamber current against polarizing voltage in the extreme near‐saturation region reveal a current rising faster than that predicted by the linear relationship. This excess current combined with conventional “two‐voltage” technique for determination of collection efficiency may result in an up to 0.7% overestimate of the saturation current for standard radiation field sizes of The measured excess current is attributed to charge multiplication in the chamber air volume and to radiation‐induced conductivity in the stem of the chamber (stem effect). These effects may be accounted for by an exponential term used in conjunction with Boag's equation for collection efficiency in pulsed beams. The semiempirical model follows the experimental data well and accounts for both the charge recombination as well as for the charge multiplication effects and the chamber stem effect.
New water equivalent liquid scintillation solutions for 3D dosimetry
Authors: Kirov A. S. , Shrinivas S. , Hurlbut C. , Dempsey J. F. , Binns W. R. , Poblete J. L.
Published: July 2002

Despite recent advances in radiochromic film and gel dosimetry techniques, radiation therapy still lacks an efficient, accurate, and convenient dose measurement method capable of measuring the dose simultaneously over a plane or a volume (3D). A possibility for creating such a 3D method based on observing scintillation photons emitted from an irradiated volume was recently reported [A. S. Kirov et al., Med. Phys.26, 1069 (1999)]. In the present article, we investigate the potential to use a liquid scintillation solution (LS) as a dose sensitive media and, simultaneously, as a water equivalent phantom material which fills the measurement volume. We show that matching water density in addition to energy absorption properties is important for using the LS solution as a phantom. Through a parametric study of the LS attenuation and absorption coefficients as well as Monte Carlo dose calculations and scintillation efficiency measurements we developed novel LS materials. For the new solutions, the calculated dose in LS is within 8% of the dose to water for depths up to 5 cm for photons having energies between 30 keV and 2 MeV. The new LS solutions, which are loaded with a Si containing compound, retain more than 85% of the scintillation efficiency of the unloaded solutions and exhibit high localization of the scintillation process. The new LS solutions are superior with respect to efficiency and water equivalence to plastic scintillator materials used in dosimetry and may be used apart from the mentioned 3D method.
A circular twin paradox
Authors: Cranor Maria B. , Heider Elizabeth M. , Price Richard H.
Published: July 2002

In the special relativistic twin paradox presented here, each twin lives on one ring of a counterrotating pair of infinitesimally separated rings, so that the twins travel on the same circular path but in opposite directions. The observers on the ring of one twin should see the clock of the other twin slowed by time dilation, but at each meeting of the twins symmetry demands that they agree on the amount of time that has passed since their previous meeting. The resolution of the paradox focuses attention on the relation of time dilation to clock synchronization.
Asymmetry of masking between complex tones and noise: The role of temporal structure and peripheral compression
Authors: Gockel Hedwig , Moore Brian C. J. , Patterson Roy D.
Published: July 2002

Thresholds for the detection of harmonic complex tones in noise were measured as a function of masker level. The rms level of the masker ranged from 40 to 70 dB SPL in 10-dB steps. The tones had a fundamental frequency (F0) of 62.5 or 250 Hz, and components were added in either cosine or random phase. The complex tones and the noise were bandpass filtered into the same frequency region, from the tenth harmonic up to 5 kHz. In a different condition, the roles of masker and signal were reversed, keeping all other parameters the same; subjects had to detect the noise in the presence of a harmonic tone masker. In both conditions, the masker was either gated synchronously with the 700-ms signal, or it started 400 ms before and stopped 200 ms after the signal. The results showed a large asymmetry in the effectiveness of masking between the tones and noise. Even though signal and masker had the same bandwidth, the noise was a more effective masker than the complex tone. The degree of asymmetry depended on F0, component phase, and the level of the masker. The maximum difference between masked thresholds for tone and noise was about 28 dB; this occurred when the F0 was 62.5 Hz, the components were in cosine phase, and the masker level was 70 dB SPL. In most conditions, the growth-of-masking functions had slopes close to 1 (on a dB versus dB scale). However, for the cosine-phase tone masker with an F0 of 62.5 Hz, a 10-dB increase in masker level led to an increase in masked threshold of the noise of only 3.7 dB, on average. We suggest that the results for this condition are strongly affected by the active mechanism in the cochlea.
Acoustic radiation force on a spherical particle in a viscous heat-conducting fluid. III. Force on a liquid drop
Authors: Doinikov Alexander A.
Published: July 2002

The general expression derived in Part I of this work [J. Acoust. Soc. Am. 101, 713–721 (1997)] for the acoustic radiation force exerted by a sound field on a spherical particle in a viscous heat-conducting fluid is applied here to a liquid drop. To demonstrate dissipative effects clearly, two limiting cases are studied. In both cases, the sound wavelength is taken to be much larger than other characteristic parameters of the system, such as the drop radius and the viscous and thermal wavelengths both outside and inside the drop. Within this assumption, two reverse situations are considered, in the first of which the dissipative effects are assumed to be weak, and in the second, to be strong. For each of these two cases, three types of incident wave are dealt with: a plane traveling wave, a plane standing wave, and a diverging spherical wave. Emphasis is given to the thermal effects on the radiation force. These are found to be greatest in the traveling and spherical waves, while in the standing wave, for both limiting cases, the thermal effects only give rise to small corrections to the leading terms due to compressibility and viscosity.