bluuebunny/crossref_metadata_2025 huggingface dataset:
C. elegans mre-11 is required for meiotic recombination and DNA repair but is dispensable for the meiotic G2 DNA damage checkpoint
Authors: Chin Gregory M. , Villeneuve Anne M.
Published: July 2002

We investigated the roles of Caenorhabditis elegans MRE-11 in multiple cellular processes required to maintain genome integrity. Although yeast Mre11 is known to promote genome stability through several diverse pathways, inviability of vertebrate cells that lack Mre11 has hindered elucidation of the in vivo roles of this conserved protein in metazoan biology. Worms homozygous for an mre-11null mutation are viable, allowing us to demonstrate in vivo requirements for MRE-11 in meiotic recombination and DNA repair. Inmre-11 mutants, meiotic crossovers are not detected, and oocyte chromosomes lack chiasmata but appear otherwise intact. γ-irradiation of mre-11 mutant germ cells during meiotic prophase eliminates progeny survivorship and induces chromosome fragmentation and other cytologically visible abnormalities, indicating a defect in repair of radiation-induced chromosome damage. Whereas mre-11 mutant germ cells are repair-deficient, they retain function of the meiotic G2 DNA damage checkpoint that triggers germ cell apoptosis in response to ionizing radiation. Although mre-11/mre-11 animals derived from heterozygous parents are viable and produce many embryos, there is a marked drop both in the number and survivorship of embryos produced by succeeding generations. This progressive loss of fecundity and viability indicates that MRE-11 performs a function essential for maintaining reproductive capacity in the species.
Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein
Authors: Yahata Tetsuro , Shao Wenlin , Endoh Hideaki , Hur Jingyung , Coser Kathryn R. , Sun Huiping , Ueda Yoshitaka , Kato Shigeaki , Isselbacher Kurt J. , Brown Myles , Shioda Toshi
Published: July 2002

CITED1, a CBP/p300-binding nuclear protein that does not bind directly to DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for estrogen-dependent transcription. When transfected, CITED1 enhanced transcriptional activation by the ligand-binding/AF2 domain of both estrogen receptor-α (ERα) and ERβ in an estrogen-dependent manner, but it affected transcriptional activities of other nuclear receptors only marginally. CITED1 bound directly to ERα in an estrogen-dependent manner through its transactivating domain, and this binding activity was separable from its p300-binding activity. CITED1 was strongly expressed in nulliparous mouse mammary epithelial cells and, when expressed in ER-positive MCF-7 breast cancer cells by transduction, exogenous CITED1 enhanced sensitivity of MCF-7 cells to estrogen, stabilizing the estrogen-dependent interaction between p300 and ERα. The estrogen-induced expression of the transforming growth factor-α (TGF-α) mRNA transcript was enhanced in the CITED1-expressing MCF-7 cells, whereas estrogen-induced expression of the mRNA transcripts for progesterone receptor or pS2 was not affected. Chromatin immunoprecipitation assay revealed that endogenous CITED1 is recruited to the chromosomal TGF-α promoter in MCF-7 cells in an estrogen-dependent manner but not to the pS2 promoter. These results suggest that CITED1 may play roles in regulation of estrogen sensitivity in a gene-specific manner.
Template boundary definition in Tetrahymena telomerase
Authors: Lai Cary K. , Miller Michael C. , Collins Kathleen
Published: July 2002

Telomerase elongates chromosome ends by addition of telomeric DNA repeats. The telomerase ribonucleoprotein can copy only a short template sequence within the telomerase RNA subunit. Here, we identify a region of telomerase RNA that is necessary for both correct 5′ template boundary definition and high affinity telomerase reverse transcriptase (TERT) interaction. We also demonstrate that TERT mutants in the RNA binding domain compromise both 5′ boundary definition and RNA binding. Our results indicate that sequence-specific interaction of a telomerase RNA element with the TERT RNA binding domain, not the active site motifs, defines the template boundary.
The Human Ribosomal Protein Genes: Sequencing and Comparative Analysis of 73 Genes
Authors: Yoshihama Maki , Uechi Tamayo , Asakawa Shuichi , Kawasaki Kazuhiko , Kato Seishi , Higa Sayomi , Maeda Noriko , Minoshima Shinsei , Tanaka Tatsuo , Shimizu Nobuyoshi , Kenmochi Naoya
Published: July 2002

The ribosome, as a catalyst for protein synthesis, is universal and essential for all organisms. Here we describe the structure of the genes encoding human ribosomal proteins (RPs) and compare this class of genes among several eukaryotes. Using genomic and full-length cDNA sequences, we characterized 73 RP genes and found that (1) transcription starts at a C residue within a characteristic oligopyrimidine tract; (2) the promoter region is GC rich, but often has a TATA box or similar sequence element; (3) the genes are small (4.4 kb), but have as many as 5.6 exons on average; (4) the initiator ATG is in the first or second exon and is within ± 5 bp of the first intron boundaries in about half of cases; and (5) 5′- and 3′-UTRs are significantly smaller (42 bp and 56 bp, respectively) than the genome average. Comparison of RP genes from humans,Drosophila melanogaster, Caenorhabditis elegans, andSaccharomyces cerevisiaerevealed the coding sequences to be highly conserved (63% homology on average), although gene size and the number of exons vary. The positions of the introns are also conserved among these species as follows: 44% of human introns are present at the same position in eitherD. melanogasterorC. elegans, suggesting RP genes are highly suitable for studying the evolution of introns.

[The sequence data described in this paper have been submitted to the DDBJ/EMBL/GenBank databases under accession nos.AB055762–AB055780,AB056456,AB061820–AB061859,AB062066–AB062071, andAB070559.]
Noise in polymer gel measurements using MRI
Authors: Low Daniel A. , Markman Jerry , Dempsey James F. , Mutic Sasa , Oldham Mark , Venkatesan Ramesh , Haacke E. Mark , Purdy James A.
Published: July 2002

With the development of conformal radiotherapy, particularly intensity modulated radiation therapy (IMRT), there is a clear need for multidimensional dosimeters. A commercial polymerizing gel, gel (MGS Research, Inc., Guilford, CT), has recently been developed that shows potential as a multi‐dimensional dosimeter. This study investigates and characterizes the noise and magnetic resonance (MR) artifacts from imaging BANG‐2 gels. Seven cylindrical vials (4 cm diam, 20 cm length) were irradiated end on in a water bath and read using MRI TE=20 ms/100 ms, TR=3000 ms). The gel calibration compared the measured depth‐dose distributions in water against the change in solvent‐proton relaxivity of the gel. A larger vial (13 cm diam, 14 cm length) was also irradiated to test the calibration accuracy in a vial of sufficient volume for dose distribution measurements. The calibration curve proved accurate to within 1.3% in determining the depth dose measured by the larger vial. An investigation of the voxel‐to‐voxel (IXIX 3 noise and sensitivity response curve showed that the voxel‐to‐voxel variation dominated the dose measurement uncertainty. The voxel‐to‐voxel standard deviation ranged from 0.2 Gy for the unirradiated gel to 0.7 Gy at 20 Gy. Slice‐to‐slice magnitude deviations were also observed corresponding to 0.2 Gy. These variations limited the overall accuracy of the gel dose measurements and warrant an investigation of more accurate MR readout sequences.
What is the optimum leaf width of a multileaf collimator?
Authors: Bortfeld Thomas , Oelfke Uwe , Nill Simeon
Published: July 2002

The following question is investigated: How narrow do the leaves of a multileaf collimator have to be such that further reduction of the leaf width does not lead to physical improvements of the dose distribution. Because of the physical principles of interaction between radiation and matter, dose distributions in radiotherapy are generally relatively smooth. According to the theory of sampling, the dose distribution can therefore be represented by a set of evenly spaced samples. The distance between the samples is identified with the distance between the leaf centers of a multileaf collimator. The optimum sampling distance is derived from the 20% to 80% field edge penumbra through the concept of the dose deposition kernel, which is approximated by a Gaussian. The leaf width of the multileaf collimator is considered to be independent from the sampling distance. Two cases are studied in detail: (i) the leaf width equals the sampling distance, which is the regular case, and (ii) the leaf width is twice the sampling distance. The practical delivery of the latter treatment geometry requires a couch movement or a collimator rotation. The optimum sampling distance equals the 20%–80% penumbra divided by 1.7 and is on the order of 1.5–2 mm for a typical 6 MV beam in soft tissue. The optimum leaf width equals this sampling distance in the regular case. A relatively small deterioration results if the leaf width is doubled, while the sampling distance remains the same. The deterioration can be corrected for by deconvolving the fluence profile with an inverse filter. Conclusions: With the help of the sampling theory and, more generally, the theory of linear systems, one can find a general answer to the question about the optimum leaf width of a multileaf collimator from a physical point of view. It is important to distinguish between the sampling distance and the leaf width. The sampling distance is more critical than the leaf width. The leaf width can be up to twice as large as the sampling width. Furthermore, the derived sampling distance can be used to select the optimum resolution of both the fluence and the dose grid in dose calculation and inverse planning algorithms.
A feasibility study of mutual information based setup error estimation for radiotherapy
Authors: Kim Jeongtae , Fessler Jeffrey A. , Lam Kwok L. , Balter James M. , Ten Haken Randall K.
Published: July 2002

We have investigated a fully automatic setup error estimation method that aligns DRRs (digitally reconstructed radiographs) from a three‐dimensional planning computed tomography image onto two‐dimensional radiographs that are acquired in a treatment room. We have chosen a MI (mutual information)‐based image registration method, hoping for robustness to intensity differences between the DRRs and the radiographs. The MI‐based estimator is fully automatic since it is based on the image intensity values without segmentation. Using 10 repeated scans of an anthropomorphic chest phantom in one position and two single scans in two different positions, we evaluated the performance of the proposed method and a correlation‐based method against the setup error determined by fiducial marker‐based method. The mean differences between the proposed method and the fiducial marker‐based method were smaller than 1 mm for translational parameters and 0.8 degree for rotational parameters. The standard deviations of estimates from the proposed method due to detector noise were smaller than 0.3 mm and 0.07 degree for the translational parameters and rotational parameters, respectively.
Quality assurance in IMRT: Importance of the transmission through the jaws for an accurate calculation of absolute doses and relative distributions
Authors: Azcona Juan Diego , Siochi R. Alfredo C. , Azinovic Ignacio
Published: July 2002

The goal of IMRT is to achieve an isodose distribution conformed to the tumor while avoiding the organs at risk. For these tasks several gantry angles are selected, each one containing a series of different leaf configurations for the multileaf collimator (MLC) (segments). Verifying the relative distributions as well as the absolute doses is an important step for quality assurance issues. We have observed that an accurate modeling of the transmission of the primary x‐ray fluence through the jaws and MLC as well as the head scatter is crucial for a precise calculation of relative doses and monitor units. Also, an inaccurate calculation of the output factor for small size segments can lead to important differences in the absolute dose for points under these segments. Incorrect models could lead to systematic errors of around 5% to 10% in the calculated monitor units and a shift in the isodose curves.
Investigation of the use of MOSFET for clinical IMRT dosimetric verification
Authors: Chuang Cynthia F. , Verhey Lynn J. , Xia Ping
Published: July 2002

With advanced conformal radiotherapy using intensity modulated beams, it is important to have radiation dose verification measurements prior to treatment. Metal oxide semiconductor field effect transistors (MOSFET) have the advantage of a faster and simpler reading procedure compared to thermoluminescent dosimeters (TLD), and with the commercial MOSFET system, multiple detectors can be used simultaneously. In addition, the small size of the detector could be advantageous, especially for point dose measurements in small homogeneous dose regions. To evaluate the feasibility of MOSFET for routine IMRT dosimetry, a comprehensive set of experiments has been conducted, to investigate the stability, linearity, energy, and angular dependence. For a period of two weeks, under a standard measurement setup, the measured dose standard deviation using the\sMOSFETs was with the mean dose being 1.00 Gy. For a measured dose range of 0.3 Gy to 4.2 Gy, the MOSFETs present a linear response, with a linearity coefficient of 0.998. Under a square field, the dose variations measured by the MOSFETs for every 10 degrees from 0 to 180 degrees is The percent depth dose (PDD) measurements were used to verify the energy dependence. The measured PDD using the MOSFETs from 0.5 cm to 34 cm depth agreed to within when compared to that of the ionization chamber. For IMRT dose verification, two special phantoms were designed. One is a solid water slab with 81 possible MOSFET placement holes, and another is a cylindrical phantom with 48 placement holes. For each IMRT phantom verification, an ionization chamber and 3 to 5 MOSFETs were used to measure multiple point doses at different locations. Preliminary results show that the agreement between dose measured by MOSFET and that calculated by Corvus is within 5% error, while the agreement between ionization chamber measurement and the calculation is within 3% error. In conclusion, MOSFET detectors are suitable for routine IMRT dose verification.
Three‐dimensional computed tomographic reconstruction using a C‐arm mounted XRII: Correction of image intensifier distortion
Authors: Fahrig R. , Moreau M. , Holdsworth D. W.
Published: July 2002

X‐ray image intensifiers (XRIIs) have many applications in diagnostic imaging including acquisition of near‐real‐time projection images of the intracranial and coronary vasculature. Recently, there has been some interest in using this projection data to generate three‐dimensional (3‐D) computed tomographic (CT) reconstructions. The XRII and x‐ray tube are rotated around the object, acquiring sufficient data for the simultaneous reconstruction of many transverse slices. Three‐dimensional reconstructions are compromised, however, if the projection data is geometrically distorted in any way. Previous studies have shown the distortion in XRIIs to be substantial and to be highly angular dependent. In this paper, we present a global correction technique which provides a table of correction coefficients for an image acquired at any arbitrary angle about the patient. The coefficients are generated using a linear least‐squares fit between the detected and known locations of a grid of small steel beads which is attached to the XRII (27 cm nominal diameter). We have performed corrections on 100 images obtained during rotation of the gantry through 200° and find that a fifth‐order polynomial provides optimum image distortion reduction (mean residual distortion of 0.07 pixels), however, fourth‐order polynomials provide sufficient distortion reduction for our application (mean residual displacement of 0.1 pixels). Using sixth‐order polynomials does not provide a statistically significant reduction in image distortion. The spatial distribution of residual distortion did not demonstrate any particular pattern over the face of the XRII. Image angle and coefficient angle must be known to within in order to keep the mean residual distortion below pixels.
A hybrid, inverse approach to the design of magnetic resonance imaging magnets
Authors: Zhao Huawei , Crozier Stuart , Doddrell David M.
Published: July 2002

This paper describes a hybrid numerical method of an inverse approach to the design of compact magnetic resonance imaging magnets. The problem is formulated as a field synthesis and the desired current density on the surface of a cylinder is first calculated by solving a Fredholm equation of the first kind. Nonlinear optimization methods are then invoked to fit practical magnet coils to the desired current density. The field calculations are performed using a semi‐analytical method. The emphasis of this work is on the optimal design of short MRI magnets. Details of the hybrid numerical model are presented, and the model is used to investigate compact, symmetric MRI magnets as well as asymmetric magnets. The results highlight that the method can be used to obtain a compact MRI magnet structure and a very homogeneous magnetic field over the central imaging volume in clinical systems of approximately 1 m in length, significantly shorter than current designs. Viable asymmetric magnet designs, in which the edge of the homogeneous region is very close to one end of the magnet system are also presented. Unshielded designs are the focus of this work. This method is flexible and may be applied to magnets of other geometries.
Splitting the wave function of a particle in a box
Authors: Gea-Banacloche Julio
Published: July 2002

This paper addresses the question of what happens to a particle in a box that is initially in the ground state, when the box is split into two slightly unequal halves. If the splitting is done sufficiently slowly, it is found that the particle always ends up in the bigger half of the box, regardless of how small the difference in sizes of the two halves may be. Approximate analytical expressions that describe the process are derived, and an optical analogy is presented.
Theory and experiments on the coupling of two Helmholtz resonators
Authors: Johansson Torbjörn A. , Kleiner Mendel
Published: July 2002

The acoustic coupling between closely located acoustic resonators can have a significant effect on the resonance properties. Examples of the influence of coupling include pipe musical instruments such as flue organs or flutes, where the coupling may affect the sound. Here, a physical model of a system of two coupled Helmholtz resonators is developed. The coupling is described by the mutual impedance between the neck openings, and an additive reflection impedance modification to the radiation impedance, which models the effect of reflections from the outer “shell” of the other resonator. The theoretical predictions show a good agreement with measurements also reported here. Finally, the effects of coupling on the present system are analyzed.
Origin of the bell-like dependence of the DPOAE amplitude on primary frequency ratio
Authors: Lukashkin Andrei N. , Russell Ian J.
Published: July 2002

For low and medium sound pressure levels (SPLs), the amplitude of the distortion product otoacoustic emission (DPOAE) recorded from guinea pigs at the 2f1-f2 frequency is maximal when f2/f1≈1.23 and decreases for lower and higher f2/f1 ratios. The high-ratio slope of the DPOAE dependence on the ratio of the primary frequencies might be anticipated since the f1 amplitude at the f2 place is expected to decrease for higher f2/f1 ratios. The low-ratio slope of the dependence at low and medium SPLs of the primaries is actually one slope of a notch. The DPOAE amplitude recovers from the notch when the f2/f1 ratio is further reduced. In two-dimensional space formed by the f2/f1 ratio, and the levels of the primaries, the notch is continuous and has a level-dependent phase transition. The notch is identical to that seen in DPOAE growth functions. Similar notches and phase transitions were observed for high-order and high-frequency DPOAEs. Theoretical analysis reveals that a single saturating nonlinearity is capable of generating similar amplitude notch and phase transition when the f2/f1 ratio is decreased because of the increase in f1 amplitude at the DPOAE generation place (f2 place). The difference between the DPOAE recorded from guinea pigs and humans is discussed in terms of different position of the operating point of the DPOAE generating nonlinearity.
Modeling of the human middle ear using the finite-element method
Authors: Koike Takuji , Wada Hiroshi , Kobayashi Toshimitsu
Published: July 2002

In this study, a three-dimensional finite-element model (FEM) of the human middle ear was established, including features of the middle ear which were not considered in the previous model, i.e., the ligaments, tendons, I–S joint, loading of the cochlea, external auditory meatus (EAM), middle-ear cavities, etc. The unknown mechanical properties of these parts and the boundary conditions were determined so that the impedance obtained from the FEM analysis resembled the measurement values. The validity of this model was confirmed by comparing the motion of the tympanic membrane and ossicles obtained by this model with the measurement data, and the effects of the newly considered features on the numerically obtained results were examined. By taking the ligaments and tendons into account and assuming that the cochlea acts as a damper, with this model it was possible to realistically reproduce complex ossicular chain movement. It was found that the middle-ear cavities did not affect the vibration mode of the tympanic membrane. Although the EAM enhanced the sound pressure applied to the tympanic membrane compared with that at the entrance of the EAM, the pressure distribution on the surface of the tympanic membrane was not affected by the EAM.
Children’s use of semantic cues in degraded listening environments
Authors: Fallon Marianne , Trehub Sandra E. , Schneider Bruce A.
Published: July 2002

Children 5 and 9 years of age and adults were required to identify the final words of low- and high-context sentences in background noise. Age-related differences in the audibility of speech signals were minimized by selecting signal-to-noise ratios (SNRs) that yielded 78% correct performance for low-context sentences. As expected, children required more favorable SNRs than adults to achieve comparable levels of performance. A more difficult listening condition was generated by adding 2 dB of noise. In general, 5-year-olds performed more poorly than did 9-year-olds and adults. Listeners of all ages, however, showed comparable gains from context in both levels of noise, indicating that noise does not impede children’s use of contextual cues.
Frequency dependence of acoustic distortion products in a locally active model of the cochlea
Authors: Kanis Luc J. , de Boer Egbert
Published: July 2002

In two-tone experiments it has been shown that acoustic distortion products are “tuned” as a function of primary frequency ratio, that is, at a certain frequency ratio a maximum in emission occurs. Several authors maintain that this “tuning” is caused by band-pass filtering of the distortion products as they are coupled back to the basilar membrane. In this paper one possible other cause for this type of tuning is brought to light. It is shown that the same kind of “tuning” is present in a locally active cochlea model without such a filtering of distortion products. In this view “tuning” becomes evident because, when the frequency ratio is near unity, the primary components tend to suppress one another, and suppress the DP, too.
Echolocation signals of the Greater Horseshoe bat (Rhinolophus ferrumequinum) in transfer flight and during landing
Authors: Tian Biao , Schnitzler Hans-Ulrich
Published: July 2002

Echolocation signals of horseshoe bats (Rhinolophidae) consist of a relatively long component of constant frequency (CF) which is preceded by an initial frequency-modulated (iFM) component and followed by a terminal frequency-modulated (tFM) component. To examine the role of these components in echolocation, four bats were trained to fly from a perch to a landing bar. A dual camera system allowed reconstruction of the flight paths in three dimensions. Echolocation signals were recorded, analyzed, and correlated with the flight behavior of the bats. It was confirmed that during flight the bats compensate the Doppler shifts which are produced by their own flight movement. In free flight they emit per wing beat one single signal of long duration, with little variation in the three signal components. In approach flight the bats reduce pulse duration and interval with decreasing target range. The iFM is not varied with respect to target range, suggesting that this component plays little role in the processing of echolocating a target of interest. The bandwidth of the tFM component is increased while its duration is shortened in proportion to decreasing target range, so that the signal–echo overlap of the FM component is avoided down to a target distance of 15 cm. These concurrent changes suggest that the tFM component is used for ranging. During the last 60 cm of the approach the bats compensated for the increase of echo SPL by lowering the emission level of the CF component by 6–9 dB and that of the tFM component by 9–11 dB per halving of range. The specific signal structure of horseshoe bats is discussed as an adaptation for the hunting of fluttering insects in highly cluttered environments.
Concurrent vowel identification. II. Effects of phase, harmonicity, and task
Authors: de Cheveigné Alain , McAdams Stephen , Marin Cécile M. H.
Published: July 2002

Subjects identified concurrent synthetic vowel pairs in four experiments. The first experiment found that improvements in vowel identification with a difference in fundamental frequency (ΔF0) do not depend on component phase. The second investigated more precisely whether phase patterns resulting from ongoing phase shifts in inharmonic stimuli can by themselves produce effects similar to those attributed to differences in harmonic state of component vowels. No such effects were found. The third experiment found that identification was better for harmonic than for inharmonic backgrounds, and that it did not depend on target harmonicity. The first three experiments employed a task in which subjects were free to report one or two vowels for each stimulus. The fourth experiment reproduced several conditions with a more classic task in which subjects had to report two vowels. Compared to the classic task, the new task gave larger effects and provided an additional measure of segregation: the number of vowels reported per stimulus. Overall, results were consistent with the hypothesis that the auditory system segregates targets by a mechanism of harmonic cancellation of competing vowels. They did not support the hypothesis of harmonic enhancement of targets. The lack of a phase effect places strong constraints on models that exploit pitch period asynchrony (PPA) or beats.
Two-tone suppression of basilar membrane vibrations in the base of the guinea pig cochlea using “low-side” suppressors
Authors: Geisler C. Daniel , Nuttall Alfred L.
Published: July 2002

The responses of the basilar membrane (BM) in the basal section of the guinea pig cochlea were measured by laser interferometry. The stimuli were pairs of harmonically related tones, presented simultaneously. One tone, at the BM’s characteristic frequency (CF) of about 17 kHz, was presented at a low intensity. The other tone, presented at various intensities, was a “low-side” suppressor, with a frequency of 0.2–8 kHz. As observed by many others, the suppressor tone, when presented at high enough intensity, reduced the magnitude of the CF component of BM displacement, sometimes dramatically. However, regardless of whether the CF component was suppressed or not, the sum of the displacement amplitudes of the CF and suppressor components was always greater than the displacement amplitude of the unsuppressed CF component. For suppressor frequencies up to 4 kHz, the suppression was both tonic and phasic, and synchronized to the suppressor period. For higher suppressor frequencies, principally tonic suppression was seen.
Perceptual segregation and pitch shifts of mistuned components in harmonic complexes and in regular inharmonic complexes
Authors: Roberts Brian , Brunstrom Jeffrey M.
Published: July 2002

It is unclear whether the perceptual segregation of a mistuned harmonic from a periodic complex tone depends specifically on harmonic relations between the other components. A procedure used previously for harmonic complexes [, J. Acoust. Soc. Am. 88, 1712–1724 (1990)] was adapted and extended to regular inharmonic complexes. On each trial, subjects heard a 12-component complex followed by a pure tone in a continuous loop. In experiment 1, a mistuning of ±4% was applied to one of the components 2–11. The complex was either harmonic, frequency shifted, or spectrally stretched. Subjects adjusted the pure tone to match the pitch of the mistuned component. Near matches were taken to indicate segregation, and were almost as frequent in the inharmonic conditions as in the harmonic case. Also, small but consistent mismatches, pitch shifts, were found in all conditions. These were similar in direction and size to earlier findings for harmonic complexes. Using a range of mistunings, experiment 2 showed that the segregation of components from regular inharmonic complexes could be sensitive to mistunings of 1.5% or less. These findings are consistent with the proposal that aspects of spectral regularity other than harmonic relations can also influence auditory grouping.
Acoustical and perceptual study of gemination in Italian stops
Authors: Esposito Anna , Di Benedetto Maria Gabriella
Published: July 2002

On the basis of theoretical considerations and results from acoustic and perceptual analyses, it is hypothesized that closure duration is the primary cue for gemination in Italian. Results of an acoustic analysis of a large number of single and geminate Italian utterances show two acoustic correlates of gemination: the length of the closure and the length of the vowel preceding the consonant. Other acoustic parameters were not systematically related to gemination. These results were validated perceptually. At the perceptual level, the above cues were used by the listeners in the geminate/nongeminate discrimination; however, closure duration played a major role. Moreover, it was found that the significant lengthening of consonant was only partially compensated by the shortening of the previous vowel and by a small lengthening of the geminate utterance with respect to the nongeminate one. This result suggests that speakers follow a sort of timing (rhythm) which is fixed in duration and depends on the number of syllables in the word: words with equal numbers of syllables do not change in utterance length, an elongated segment being partly compensated by the shortening of another. This process seems to be applied also perceptually suggesting that the timing (rhythm) of a language is also an auditory attitude.
Analysis of the f2−f1 and 2 f1−f2 distortion components generated by the hair cell mechanoelectrical transducer: Dependence on the amplitudes of the primaries and feedback gain
Authors: Lukashkin Andrei N. , Russell Ian J.
Published: July 2002

This paper describes the pattern of f2−f1 and 2 f1−f2 components at the output of the nonlinear hair cell mechanoelectrical transducer when the input consists of two sinusoidal signals. The mechanoelectrical transducer was represented by a second-order Boltzmann function. It is shown that some experimental observations, which have been cited to prove the existence of two discrete sources of distortion product otoacoustic emissions in the cochlea, can be produced by a single nonlinearity. These observations include the pattern of magnitude and phase “notches” in the growth functions of the distortion product otoacoustic emissions when measured in the two-dimensional space of the amplitudes of the two primaries. A single saturating nonlinearity also explains the distinctive response of the distortion product otoacoustic emissions to the decreasing gain of the cochlear amplifier. A possible basis for the differences in distortion product otoacoustic emissions, which have been measured in humans and rodents, is discussed.
Within-channel cues in comodulation masking release (CMR): Experiments and model predictions using a modulation-filterbank model
Authors: Verhey Jesko L. , Dau Torsten , Kollmeier Birger
Published: July 2002

Experiments and model calculations were performed to study the influence of within-channel cues versus across-channel cues in comodulation masking release (CMR). A class of CMR experiments is considered that are characterized by a single (unmodulated or modulated) bandpass noise masker with variable bandwidth centered at the signal frequency. A modulation-filterbank model suggested by Dau et al. [J. Acoust. Soc. Am. 102, 2892–2905 (1997)] was employed to quantitatively predict the experimental data. Effects of varying masker bandwidth, center frequency, modulator bandwidth, modulator type, and signal duration on CMR were examined. In addition, the effect of band limiting the noise before or after modulation was shown to influence the CMR in the same way as a systematic variation of the modulation depth. It is demonstrated that a single-channel analysis, which analyzes only the information from one peripheral channel, quantitatively accounts for the CMR in most cases, indicating that an across-channel process is generally not necessary for simulating results from this class of CMR experiments. True across-channel processes may be found in another class of CMR experiments.
Internal circulation in a drop in an acoustic field
Authors: Zhao Hong , Sadhal S. S. , Trinh Eugene H.
Published: July 2002

An investigation of the internal flow field for a drop at the antinode of a standing wave has been carried out. The main difference from the solid sphere case is the inclusion of the shear stress and velocity continuity conditions at the liquid–gas interface. To the leading order of calculation, the internal flow field was found to be quite weak. Also, this order being fully time dependent has a zero mean flow. At the next higher order, steady internal flows are predicted and, as in the case of a solid sphere, there is a recirculating layer consisting of closed streamlines near the surface. In the case of a liquid drop, however, the behavior of this recirculating Stokes layer is quite interesting. It is predicted that the layer ceases to have recirculation when |M|>522[2+5(μ̂/μ)], where μ̂ is the liquid viscosity, μ is the exterior gas-phase viscosity, and M is the dimensionless frequency parameter for the gas phase, defined by M=iωa2ρ/μ, with a being the drop radius. Thorough experimental confirmation of this interesting new development needs to be conducted. Although it seems to agree with many experiments with levitated drops where no recirculating layer has been clearly observed, a new set of experiments for specifically testing this interesting development need to be carried out.
Performance measurements on a thermoacoustic refrigerator driven at high amplitudes
Authors: Poese Matthew E. , Garrett Steven L.
Published: July 2002

Since the power density in a thermoacoustic device is proportional to the square of the acoustic Mach number, there is strong motivation to design thermoacoustic refrigerators to operate at larger pressure amplitudes. Measurements are reported of a modified version of the Space Thermo-Acoustic Refrigerator (STAR), driven at peak-to-mean pressure ratios up to 6%. This pressure ratio corresponds to 30 W of cooling power—five times as large as reported for STAR in 1993. The results of these measurements are compared to a DELTAE computer model of the low-amplitude (linear) performance that matches experimental conditions on a point-by-point basis. It is found that there is a small but measurable deviation in heat pumping power from the power predicted with a linear acoustic computer model at moderate amplitudes. This deviation in heat pumping power at 6% pressure ratio is about 23%. A large disagreement in the acoustic power needed to attain a specific pressure ratio is found between measured data and DELTAE results. An overview of the instrumentation, including a measurement of exhaust heat with an absolute accuracy of 65 mW, is also presented.
Viscoelastic Hysteresis. Part I. Model Predictions
Authors: Bird R. Byron , Marsh B. Duane
Published: July 2002

Hysteresis loops on a shear stress versus shear rate plot have been reported by numerous investigators studying polymeric fluids. Both clockwise and counterclockwise loops have been observed. Currently available nonlinear viscoelastic models can be used to derive expressions for these hysteresis loops as well as for the corresponding normal stress hysteresis loops. It is suggested that the hysteresis loop experiment may be particularly useful for the testing of nonlinear viscoelastic models.
An Integral Constitutive Equation Based on Molecular Network Theory
Authors: Meister Bernard J.
Published: July 2002

A new constitutive equation for concentrated polymer solutions and melts is presented that is based on the entanglement theory of Lodge. The strain rate dependence of the memory function is determined using a physical hypothesis of interacting spheres where the spheres represent spheres of influence of the network junctions. The resulting equation has one constant that can be estimated theoretically in addition to the natural relaxation spectrum. At high strain rates, a second empirical constant is introduced to account for the orientation of the spheres of influence. Predictions of the equation and the equations of Bogue, Bird-Carreau, and Tanner were compared to steady and transient shear stress and normal stress data obtained on a Weissenberg rheogoniometer. The new equation fits nonlinear transient data more satisfactorily than other equations of similar complexity.
Singular behavior of Rouse-like spectra
Authors: Denneman A. I. M. , Jongschaap R. J. J. , Mellema J.
Published: July 2002

In this study an extended Rouse formalism is used to obtain results belonging to (i) linear chains (K beads; K−1 Hookean springs), (ii) K×K cubic networks, or (iii) K×K×K cubes immersed in a Newtonian fluid. These three systems are subjected to small-amplitude oscillatory shear flow of frequency ω and the resulting dynamic moduli G′(ω) and G″(ω) show significant differences. For large K, the corresponding relaxation spectra H(λ) appear to be smooth functions of time λ, in which some obvious discontinuities are observed, i.e., the so-called Van Hove singularities (well known in solid-state physics). Actually, for these three systems a relation is obtained between H(λ) and the frequency spectra g(ω) used in solid-state physics.
Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention
Authors: Marston Nicholas A. , Pirruccello James P. , Melloni Giorgio E. M. , Koyama Satoshi , Kamanu Frederick K. , Weng Lu-Chen , Roselli Carolina , Kamatani Yoichiro , Komuro Issei , Aragam Krishna G. , Butterworth Adam S. , Ito Kaoru , Lubitz Steve A. , Ellinor Patrick T. , Sabatine Marc S. , Ruff Christian T.
Published: December 2022

Importance

The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.

Objective

To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.

Design, Setting, and Participants

This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.

Exposures

Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (≥20%).

Main Outcomes and Measures

Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).

Results

A total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.

Conclusions and Relevance

Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.
Validation of a Deep Learning–Based Model to Predict Lung Cancer Risk Using Chest Radiographs and Electronic Medical Record Data
Authors: Raghu Vineet K. , Walia Anika S. , Zinzuwadia Aniket N. , Goiffon Reece J. , Shepard Jo-Anne O. , Aerts Hugo J. W. L. , Lennes Inga T. , Lu Michael T.
Published: December 2022

Importance

Lung cancer screening with chest computed tomography (CT) prevents lung cancer death; however, fewer than 5% of eligible Americans are screened. CXR-LC, an open-source deep learning tool that estimates lung cancer risk from existing chest radiograph images and commonly available electronic medical record (EMR) data, may enable automated identification of high-risk patients as a step toward improving lung cancer screening participation.

Objective

To validate CXR-LC using EMR data to identify individuals at high-risk for lung cancer to complement 2022 US Centers for Medicare & Medicaid Services (CMS) lung cancer screening eligibility guidelines.

Design, Setting, and Participants

This prognostic study compared CXR-LC estimates with CMS screening guidelines using patient data from a large US hospital system. Included participants were persons who currently or formerly smoked cigarettes with an outpatient posterior-anterior chest radiograph between January 1, 2013, and December 31, 2014, with no history of lung cancer or screening CT. Data analysis was performed between May 2021 and June 2022.

Exposures

CXR-LC lung cancer screening eligibility (previously defined as having a 3.297% or greater 12-year risk) based on inputs (chest radiograph image, age, sex, and whether currently smoking) extracted from the EMR.

Main Outcomes and Measures

6-year incident lung cancer.

Results

A total of 14 737 persons were included in the study population (mean [SD] age, 62.6 [6.8] years; 7154 [48.5%] male; 204 [1.4%] Asian, 1051 [7.3%] Black, 432 [2.9%] Hispanic, 12 330 [85.2%] White) with a 2.4% rate of incident lung cancer over 6 years (361 patients with cancer). CMS eligibility could be determined in 6277 patients (42.6%) using smoking pack-year and quit-date from the EMR. Patients eligible by both CXR-LC and 2022 CMS criteria had a high rate of lung cancer (83 of 974 patients [8.5%]), higher than those eligible by 2022 CMS criteria alone (5 of 177 patients [2.8%]; P < .001). Patients eligible by CXR-LC but not 2022 CMS criteria also had a high 6-year incidence of lung cancer (121 of 3703 [3.3%]). In the 8460 cases (57.4%) where CMS eligibility was unknown, CXR-LC eligible patients had a 5-fold higher rate of lung cancer than ineligible (127 of 5177 [2.5%] vs 18 of 2283 [0.5%]; P < .001). Similar results were found in subgroups, including female patients and Black persons.

Conclusions and Relevance

Using routine chest radiographs and other data automatically extracted from the EMR, CXR-LC identified high-risk individuals who may benefit from lung cancer screening CT.
Variation in Resident Operative Autonomy at Veterans Affairs Hospitals
Authors: Portuondo Jorge I. , Whitlock Richard S. , Mehl Steven C. , Massarweh Nader N.
Published: December 2022

This cohort study examines resident involvement in the care of US veterans who underwent noncardiac surgery.
Effect of surgery on the survival of elderly patients with early stage pancreatic cancer: A propensity‐matched analysis
Authors: Wu Jiali , Xie Zishan , Lei Chuqian , Yu Liwa , Huang Rui , Li Ming , Yuan Lu , Zhang Weixing
Published: December 2022

Background and objectives

Research about the effect of surgery in geriatric patients with early stage pancreatic ductal adenocarcinoma (PDAC) is limited, and it remains a subject of much debate. The purpose of this study was to evaluate the role of surgery on the survival of elderly patients with T1‐3N0M0 PDAC and to further investigate the prognosis of these patients undergoing different surgical methods.

Methods

Patients aged ≥65 with T1‐3N0M0 PDAC diagnosed in 2004–2016 were collected from the Surveillance, Epidemiology, and End Results database. The imbalance of baseline characteristics was reduced by propensity score matching. We used the log‐rank tests to evaluate overall survival (OS) and cancer‐specific survival (CSS) among different groups. Univariate and multivariate Cox regression analysis was utilized to explore prognostic factors in PDAC.

Results

In total, 6363 patients were enrolled. After matching, 1110 patients were paired. We found that surgery could provide better survival (p < 0.001). Moreover, compared with those who underwent partial resection or larger resection, patients who underwent local tumor destruction had poorer OS and CSS (p < 0.001). However, no statistically significant survival differences were shown between the partial resection group and the larger resection group (p < 0.001).

Conclusion

Surgical intervention could confer a survival benefit to elderly patients with early stage PDAC. Additionally, these patients could benefit from more radical operations, and radical operations with reasonable extents are advocated rather than too aggressive methods.