bluuebunny/crossref_metadata_2025 huggingface dataset:
The histone H4 acetyltransferase MOF uses a C2HC zinc finger for substrate recognition
Authors: Akhtar Asifa , Becker Peter B
Published: July 2002

Site‐specific acetylation of histone H4 by MOF is central to establishing the hyperactive male X chromosome in Drosophila. MOF belongs to the MYST family of histone acetyltransferases (HATs) characterized by an unusual C2HC‐type zinc finger close to their HAT domains. The function of these rare zinc fingers is unknown. We found that this domain is essential for HAT activity, in addition to the established catalytic domain. MOF uses its zinc finger to contact the globular part of the nucleosome as well as the histone H4 N‐terminal tail substrate. Point mutations that leave the zinc‐finger structure intact nevertheless abolish its interaction with the nucleosome. Our data document a novel role of the C2HC‐type finger in nucleosome binding and HAT activity.
Visualization of recombination intermediates produced by RAD52‐mediated single‐strand annealing
Authors: Van Dyck Eric , Stasiak Alicja Z , Stasiak Andrzej , West Stephen C
Published: July 2002

Double‐strand breaks (DSBs) occur frequently during DNA replication. They are also caused by ionizing radiation, chemical damage or as part of the series of programmed events that occur during meiosis. In yeast, DSB repair requires RAD52, a protein that plays a critical role in homologous recombination. Here we describe the actions of human RAD52 protein in a model system for single‐strand annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules. Purified human RAD52 protein binds resected DSBs and promotes associations between complementary DNA termini. Heteroduplex intermediates of these recombination reactions have been visualized by electron microscopy, revealing the specific binding of multiple rings of RAD52 to the resected termini and the formation of large protein complexes at heteroduplex joints formed by RAD52‐mediated annealing.
Trees tell of past climates: but are they speaking less clearly today?
Authors: Briffa K. R. , Schweingruber F. H , Jones P. D. , Osborn T. J. , Harris I. C. , Shiyatov S. G. , Vaganov E. A. , Grudd H.
Published: July 2002

The annual growth of trees, as represented by a variety of ring–width, densitometric, or chemical parameters, represents a combined record of different environmental forcings, one of which is climate. Along with climate, relatively large–scale positive growth influences such as hypothesized ‘fertilizationrsquo; due to increased levels of atmospheric carbon dioxide or various nitrogenous compounds, or possibly deleterious effects of ‘acid rain’ or increased ultra–violet radiation, might all be expected to exert some influence on recent tree growth rates. Inferring the details of past climate variability from tree–ring data remains a largely empirical exercise, but one that goes hand–in–hand with the development of techniques that seek to identify and isolate the confounding influence of local and larger–scale non–climatic factors.

By judicious sampling, and the use of rigorous statistical procedures, dendroclimatology has provided unique insight into the nature of past climate variability, but most significantly at interannual, decadal, and centennial timescales. Here, examples are shown that illustrate the reconstruction of annually resolved patterns of past summer temperature around the Northern Hemisphere, as well as some more localized reconstructions, but ones which span 1000 years or more. These data provide the means of exploring the possible role of different climate forcings; for example, they provide evidence of the large–scale effects of explosive volcanic eruptions on regional and hemispheric temperatures during the last 400 years.

However, a dramatic change in the sensitivity of hemispheric tree–growth to temperature forcing has become apparent during recent decades, and there is additional evidence of major tree–growth (and hence, probably, ecosystem biomass) increases in the northern boreal forests, most clearly over the last century. These possibly anthropogenically related changes in the ecology of tree growth have important implications for modelling future atmospheric CO2concentrations. Also, where dendroclimatology is concerned to reconstruct longer (increasingly above centennial) temperature histories, such alterations of ‘normal’ (pre–industrial) tree–growth rates and climate–growth relationships must be accounted for in our attempts to translate the evidence of past tree growth changes.
The proteasome: a macromolecular assembly designed for controlled proteolysis
Authors: Zwickl P. , Voges D. , Baumeister W.
Published: July 2002

In eukaryotic cells, the vast majority of proteins in the cytosol and nucleus are degraded via the proteasome–ubiquitin pathway. The 26S proteasome is a huge protein degradation machine of 2.5 MDa, built of approximately 35 different subunits. It contains a proteolytic core complex, the 20S proteasome and one or two 19S regulatory complexes which associate with the termini of the barrel–shaped 20S core. The 19S regulatory complex serves to recognize ubiquitylated target proteins and is implicated to have a role in their unfolding and translocation into the interior of the 20S complex where they are degraded into oligopeptides. While much progress has been made in recent years in elucidating the structure, assembly and enzymatic mechanism of the 20S complex, our knowledge of the functional organization of the 19S regulator is rather limited. Most of its subunits have been identified, but specific functions can be assigned to only a few of them.
Control of NF–κB transcriptional activation by signal induced proteolysis of IκBα
Authors: Hay R. T. , Vuillard L. , Desterro J. M. P. , Rodriguez M. S.
Published: July 2002

In unstimulated cells the transcription factor NF–κB is held in the cytoplasm in an inactive state by IκB inhibitor proteins. Ultimately activation of NF–κB is achieved by ubiquitination and proteasome–mediated degradation of IκBα and we have therefore investigated factors which control this proteolysis. Signal–induced degradation of IκBα exposes the nuclear localization signal of NF–κB, thus allowing it to translocate into the nucleus and activate transcription from responsive genes. An autoregulatory loop is established when NF–κB induces expression of the IκBα gene and newly synthesized IκBα accumulates in the nucleus where it negatively regulates NF–κB–dependent transcription. As part of this post–induction repression, the nuclear export signal on IκBα mediates transport of NF–κB–IκBα complexes from the nucleus to the cytoplasm. As nuclear export of IκBα is blocked by leptomycin B this drug was used to examine the effect of cellular location on susceptibility of IκBα to signal–induced degradation. In the presence of leptomycin B, IκBα is accumulated in the nucleus and in this compartment is resistant to signal–induced degradation. Thus signal–induced degradation of IκBα is mainly, if not exclusively a cytoplasmic process. An efficient nuclear export of IκBα is therefore essential for maintaining a low level of IκBα in the nucleus and allowing NF–κB to be transcriptionally active upon cell stimulation. We have detected a modified form of IκBα, conjugated to the small ubiquitin–like protein SUMO–1, which is resistant to signal–induced degradation. SUMO–1 modified IκBα remains associated with NF–κB and thus overexpression of SUMO–1 inhibits the signal–induced activation of NF–κB–dependent transcription. Reconstitution of the conjugation reaction with highly purified proteins demonstrated that in the presence of a novel E1 SUMO–1 activating enzyme, Ubch9 directly conjugated SUMO–1 to IκBα on residues K21 and K22, which are also used for ubiquitin modification. Thus, while ubiquitination targets proteins for rapid degradation, SUMO–1 modification acts antagonistically to generate proteins resistant to degradation.
Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway
Authors: Reizis Boris , Leder Philip
Published: July 2002

The Notch signaling pathway regulates the commitment and early development of T lymphocytes. We studied Notch-mediated induction of thepre-T cell receptor α(pTa) gene, a T-cell-specific transcriptional target of Notch. ThepTaenhancer was activated by Notch signaling and contained binding sites for its nuclear effector, CSL. Mutation of the CSL-binding sites abolished enhancer induction by Notch and delayed the up-regulation ofpTatransgene expression during T cell lineage commitment. These results show a direct mechanism of stage- and tissue-specific gene induction by the mammalian Notch/CSL signaling pathway.
Identification of Wound Healing/Regeneration Quantitative Trait Loci (QTL) at Multiple Time Points that Explain Seventy Percent of Variance in (MRL/MpJ and SJL/J) Mice F2 Population
Authors: Masinde Godfred L. , Li Xinmin , Gu Weikuan , Davidson Heather , Mohan Subburaman , Baylink David J.
Published: July 2002

Studies on genetic mechanisms of wound healing in mammals are very few, although injury is a leading cause of the global burden of disease. In this study, we performed a high-density, genome-wide scan using 633 (MRL/MPJ × SJL/J) F2 intercross at multiple time points (days 15, 21, and 25) to identify quantitative trait loci (QTL) involved in wound healing/regeneration. The hypothesis of the study was that QTL and unique epistatic interactions are involved at each time point to promote wound healing/regeneration. Ten QTL were identified from chromosomes 1, 4, 6, 7, 9, and 13. Of the 10 QTL, eight from chromosomes 1, 4, 6, and 9 were novel as compared to QTL identified in the McBrearty et al. (1998) study. The 10 QTL altogether explained 70% of variance in F2 mice. The same QTL were identified at each time point, with simple linear correlation between days 15, 21, and 25, showing very high significant relationships (R >0.92,P <0.0001). Unique epistatic interactions were identified at each time point except those from chromosomes 4, 6, 9, and 13 that were found at all three time points, showing that some loci are involved at all the three time points of wound healing (days 15, 21, and 25). Therefore, loci-to-loci interactions may play a major role in wound healing. Information from these studies may help in the identification of genes that could be involved in wound healing/regeneration.
viewGene: A Graphical Tool for Polymorphism Visualization and Characterization
Authors: Kashuk Carl , SenGupta Sanghamitra , Eichler Evan , Chakravarti Aravinda
Published: July 2002

The human genome project is producing an enormous amount of sequence data, based on which single base changes between individuals can be identified. Unfortunately, computer tools that were adequate for sequence assembly are less than ideal for the characterization of polymorphism data [single nucleotide (snp) or insertion/deletion (indel)] and other sequence features, and their relationship to each other. We have developed viewGeneas a flexible tool that takes input from a number of sequence formats and analysis programs (Genbank, FASTA,RepeatMasker, Cross match, BLAST, user-defined data) to construct a sequence reference scaffold that can be viewed through a simple graphical interface. polymorphisms generated from many sources can be added to this scaffold through the same sequence formats, with a variety of options to control what is displayed. Large amounts of polymorphism data can be organized so that patterns and haplotypes can be readily discerned. in our laboratory,viewGene has been used to view annotated genbank records, find nonrepetitive sequence fragments for polymorphism detection, and visualize similarity search results. Manipulation, cross-referencing, and haplotype viewing of snp data are essential for quality assessment and identification of variants associated with genetic disease, and viewGene provides all three of these important functions.
Miniature tissue‐equivalent proportional counters for BNCT and BNCEFNT dosimetry
Authors: Burmeister Jay , Kota Chandrasekhar , Maughan Richard L. , Waker Anthony J.
Published: July 2002

A dual miniature tissue‐equivalent proportional counter (TEPC) system has been developed to facilitate microdosimetry for Boron Neutron Capture Therapy (BNCT). This system has been designed specifically to allow the analysis of the single event charged particle spectrum in phantom in high intensity BNCT beams and to provide this microdosimetric information with excellent spatial resolution. Paired A‐150 and‐loaded A‐150 TEPCs with 12.3 mm3collecting volumes have been constructed. These TEPCs allow more accurate neutron dosimetry than current techniques, offer a direct measure of the boron neutron capture dose, and provide a framework for predicting the biological effectiveness of the absorbed dose. Design aspects and characterization of these detectors are reviewed, along with an exposition of the advantages of microdosimetry using these detectors over conventional dosimetry methods. In addition, the utility of this technique for boron neutron capture enhancement of fast neutron therapy (BNCEFNT) is discussed.
Three‐dimensional optimization of treatment planning for gamma unit treatment system
Authors: Shu Huazhong , Yan Yulong , Luo Limin , Bao Xudong
Published: July 2002

During a treatment using the Leksell gamma unit, the physician and physicist need to determine a treatment plan by changing the parameters such as collimator sizes, the position of isocenters and isocenters' weights. This is a complex problem because the set of parameters is large, especially when targets are geometrically close to a critical structure. For this reason, we present here an optimization algorithm, namely the multiplier penalty method, to mathematically determine those parameters. Two cases are presented in this article: the first one is really planned by a physicist in a clinical treatment, and is redone in our optimization algorithm to show the effectiveness of this method; the second one is theoretical where a critical structure is placed close to the target volume. The results show that this method achieves an excellent conformation to the specified isodose curve with the contour of the target volume, allowing minimal damage to surrounding healthy tissue.
Relationship between acoustic aperture size and tumor conditions for external ultrasound hyperthermia
Authors: Lin Win‐Li , Yen Jia‐Yush , Chen Yung‐Yaw , Jin Kuo‐Wen , Shieh Ming‐Jium
Published: July 2002

External ultrasound hyperthermia is a very flexible modality for heating deep‐seated tumors due to its deep penetration and focusing ability. However, under the constraints of the available acoustic aperture size for the ultrasonic beam, ultrasonic attenuation, as well as other anatomic properties, it may not be able to deliver sufficient ultrasonic energy to heat a large tumor located in a deep region without overheating the normal tissue between the tumor and the aperture. In this work, we employ a simulation program based on the steady‐state bioheat transfer equation and an ideal ultrasound power deposition (a cone with convergent/divergent shape) to examine the relationship between the minimal diameter of the acoustic aperture and the tumor conditions. Tissue temperatures are used to determine the appropriate aperture diameter and the input power level for a given set of tumor conditions. Due to the assumed central axis symmetry of the power intensity deposition and anatomic properties, a two‐dimensional simulation program is utilized. Factors determining the acoustic aperture diameter and the input power level considered here are the tumor size, tumor depth, ultrasonic attenuation in tissue, blood perfusion, and temperature of the surface cooling water. Simulation results demonstrate that tumor size, tumor depth, and ultrasonic attenuation are major factors affecting the aperture diameter of the ultrasonic beam to obtain an appropriate temperature distribution, while blood perfusion and the temperature of the surface cooling water are the minor factors. Plots of the effects of these factors can be used as the guideline for designing an optimal ultrasound heating system, arranging the transducers, and planning further treatments.
Accurate condensed history Monte Carlo simulation of electron transport. I. EGSnrc, the new EGS4 version
Authors: Kawrakow I.
Published: July 2002

In this report a new EGS4 version, called EGSnrc to reflect the substantial changes made to the original code is reported, which incorporates a new any‐angle multiple elastic scattering theory, an improved electron‐step algorithm, a correct implementation of the fictitious cross section method for sampling distances between discrete interactions, a more accurate evaluation of energy loss, as well as an exact boundary crossing algorithm. It is demonstrated that EGSnrc allows for an artifact free Monte Carlo simulation of ion chamber response and backscattering, situations that have been considered in the past as the two of the most stringent tests of condensed history Monte Carlo codes. A detailed discussion of the effect of the various components of the condensed history simulation of electron transport on the simulated ion chamber response is given in the accompanying paper.
Scanning thermoacoustic tomography in biological tissue
Authors: Ku Geng , Wang Lihong V.
Published: July 2002

Microwave‐induced thermoacoustic tomography was explored to image biological tissue. Short microwave pulses irradiated tissue to generate acoustic waves by thermoelastic expansion. The microwave‐induced thermoacoustic waves were detected with a focused ultrasonic transducer. Each time‐domain signal from the ultrasonic transducer represented a one‐dimensional image along the acoustic axis of the ultrasonic transducer similar to an ultrasonic A‐scan. Scanning the system perpendicularly to the acoustic axis of the ultrasonic transducer would generate multi‐dimensional images. Two‐dimensional tomographic images of biological tissue were obtained with 3‐GHz microwaves. The axial and lateral resolutions were characterized. The time‐domain piezo‐electric signal from the ultrasonic transducer in response to the thermoacoustic signal was simulated theoretically, and the theoretical result agreed with the experimental result very well.
Interrelations among distortion-product phase-gradient delays: Their connection to scaling symmetry and its breaking
Authors: Shera Christopher A. , Talmadge Carrick L. , Tubis Arnold
Published: July 2002

Distortion-product-otoacoustic-emission (DPOAE) phase-versus-frequency functions and corresponding phase-gradient delays have received considerable attention because of their potential for providing information about mechanisms of emission generation, cochlear wave latencies, and characteristics of cochlear tuning. The three measurement paradigms in common use (fixed-f1, fixed-f2, and fixed-f2/f1) yield significantly different delays, suggesting that they depend on qualitatively different aspects of cochlear mechanics. In this paper, theory and experiment are combined to demonstrate that simple phenomenological arguments, which make no detailed mechanistic assumptions concerning the underlying cochlear mechanics, predict relationships among the delays that are in good quantitative agreement with experimental data obtained in guinea pigs. To understand deviations between the simple theory and experiment, a general equation is found that relates the three delays for any deterministic model of DPOAE generation. Both model-independent and exact, the general relation provides a powerful consistency check on the measurements and a useful tool for organizing and understanding the structure in DPOAE phase data (e.g., for interpreting the relative magnitudes and intensity-dependencies of the three delays). Analysis of the general relation demonstrates that the success of the simple, phenomenological approach can be understood as a consequence of the mechanisms of emission generation and the approximate local scaling symmetry of cochlear mechanics. The general relation is used to quantify deviations from scaling manifest in the measured phase-gradient delays; the results indicate that deviations from scaling are typically small and that both linear and nonlinear mechanisms contribute significantly to these deviations. Intensity-dependent mechanisms contributing to deviations from scaling include cochlear-reflection and wave-interference effects associated with the mixing of distortion- and reflection-source emissions (as in DPOAE fine structure). Finally, the ratio of the fixed-f1 and fixed-f2 phase-gradient delays is shown to follow from the choice of experimental paradigm and, in the scaling limit, contains no information about cochlear physiology whatsoever. These results cast considerable doubt on the theoretical basis of recent attempts to use relative DPOAE phase-gradient delays to estimate the bandwidths of peripheral auditory filters.
Use of nonsingular boundary integral formulation for reducing errors due to near-field measurements in the boundary element method based near-field acoustic holography
Authors: Kang Sung-Chon , Ih Jeong-Guon
Published: July 2002

In the conformal near-field acoustic holography (NAH) using the boundary element method (BEM), the transfer matrix relating the vibro-acoustic properties of source and field depends solely on the geometrical condition of the problem. This kind of NAH is known to be very powerful in dealing with the sources having irregular shaped boundaries. When the vibro-acoustic source field is reconstructed by using this conformal NAH, one tends to position the sensors as close as possible to the source surface in order to get rich information on the nonpropagating wave components. The conventional acoustic BEM based on the Kirchhoff–Helmholtz integral equation has the singularity problem in the close near field of the source surface. This problem stems from the singular kernel of the Green function of the boundary integral equation (BIE) and the singularity can influence the reconstruction accuracy greatly. In this paper, the nonsingular BIE is introduced to the NAH calculation and the holographic BIE is reformulated. The effectiveness of nonsingular BEM has been investigated for the reduction of reconstruction error. Through interior and exterior examples, it is shown that the resolution of predicted field pressure could be improved in the close near field by employing the nonsingular BIE. Because the BEM-based NAH inevitably requires the field pressure measured in the close proximity to the source surface, the present approach is recommended for improving the resolution of the reconstructed source field.
Boundary element method calculation of individual head-related transfer function. I. Rigid model calculation
Authors: Katz Brian F. G.
Published: July 2002

Human spatial perception of sound is a complex phenomenon. The Head-Related Transfer Function (HRTF) is a vital component to spatial sound perception. In order improve the understanding of the correlation between the HRTF and specific geometry of the head and pinna, a Boundary Element Method (BEM) has been used to calculate a portion of the HRTF of an individual based on precise geometrical data. Advantages of this approach include the ability to alter the geometry of the individual through the model in ways which are not possible with real subjects. Several models are used in the study, including a head with no pinna and several sized spheres. Calculations are performed for various source locations around the head. Results are presented for rigid model cases. Effects of variations on impedance and comparisons to measured data will be presented in the subsequent paper.
Quantifying the implications of nonlinear cochlear tuning for auditory-filter estimates
Authors: Heinz Michael G. , Colburn H. Steven , Carney Laurel H.
Published: July 2002

The relation between auditory filters estimated from psychophysical methods and peripheral tuning was evaluated using a computational auditory-nerve (AN) model that included many of the response properties associated with nonlinear cochlear tuning. The phenomenological AN model included the effects of dynamic level-dependent tuning, compression, and suppression on the responses of high-, medium-, and low-spontaneous-rate AN fibers. Signal detection theory was used to evaluate psychophysical performance limits imposed by the random nature of AN discharges and by random-noise stimuli. The power-spectrum model of masking was used to estimate psychophysical auditory filters from predicted AN-model detection thresholds for a tone signal in fixed-level notched-noise maskers. Results demonstrate that the role of suppression in broadening peripheral tuning in response to the noise masker has implications for the interpretation of psychophysical auditory-filter estimates. Specifically, the estimated psychophysical auditory-filter equivalent rectangular bandwidths (ERBs) that were derived from the nonlinear AN model with suppression always overestimated the ERBs of the low-level peripheral model filters. Further, this effect was larger for an 8-kHz signal than for a 2-kHz signal, suggesting a potential characteristic-frequency (CF) dependent bias in psychophysical estimates of auditory filters due to the increase in strength of cochlear nonlinearity with increases in CF.
Determination of embedded layer properties using adaptive time-frequency domain analysis
Authors: Wang L. , Xie B. , Rokhlin S. I.
Published: July 2002

A general model for determination of the complete set of acoustical and geometrical properties of an isotropic layer embedded between isotropic or anisotropic multilayered solids is developed. These properties include density, longitudinal and shear elastic moduli, layer thickness, and loss factors, simultaneously determined from two measurements, one at normal and one at oblique incidence. The inversion model is an extension of the method proposed by Lavrentyev and Rokhlin [J. Acoust. Soc. Am. 102, 3467 (1997)] which is applicable to thick substrates. In this new method, the inversion model mimics an experiment by using the same time-domain gating of the signal reflected from the embedded layer. This allows application of this method to layered solids when reflections from different layers overlap in the time domain. The sensitivity of the method, its stability against data scatter, and the effect of the oblique incident angle are evaluated. The effect of plane-wave approximation versus beam approximation in the inverse algorithm is discussed. Experimental results are given to demonstrate examples of adhesive layer property reconstruction. © 2002 Acoustical Society of America.
Speech recognition at simulated soft, conversational, and raised-to-loud vocal efforts by adults with cochlear implants
Authors: Skinner Margaret W. , Holden Laura K. , Holden Timothy A. , Demorest Marilyn E. , Fourakis Marios S.
Published: July 2002

Ten postlinguistically deaf adults who used the Nucleus Cochlear Implant System and SPEAK speech coding strategy responded to vowels, consonants, words, and sentences presented sound-only at 70, 60, and 50 dB sound-pressure level. Highest group mean scores were at a raised-to-loud level of 70 dB for consonants (73%), words (44%), and sentences (87%); the highest score for vowels (70%) was at a conversational level of 60 dB. Lowest group mean scores were at a soft level of 50 dB for vowels (56%), consonants (47%), words (10%), and sentences (29%); all except subject 7 had some open-set speech recognition at this level. For the conversational level (60 dB), group mean scores for sentences and words were 72% and 29%, respectively. With this performance and sound-pressure level, it was observed that these subjects communicated successfully in a variety of listening situations. Given these subjects’ speech recognition scores at 60 dB and the fact that 70 dB does not simulate the vocal effort used in everyday speaking situations, it is suggested that cochlear implant candidates and implantees be evaluated with speech tests presented at 60 dB instead of the customary 70 dB sound-pressure level to simulate benefit provided by implants in everyday life. Analysis of individuals’ scores at the three levels for the four speech materials revealed different patterns of speech recognition among subjects (e.g., subjects 1 and 5). Future research on the relation between stimuli, sound processing, and subjects’ responses associated with these different patterns may provide guidelines to select parameter values with which to map incoming sound onto an individual’s electrical dynamic range between threshold and maximum acceptable loudness level to improve speech recognition.
Determination of elastic moduli, density, attenuation, and thickness of a layer using ultrasonic spectroscopy at two angles
Authors: Lavrentyev Anton I. , Rokhlin Stanislav I.
Published: July 2002

An ultrasonic method for determination of the complete set of acoustical and geometrical properties of an isotropic layer embedded between two known materials (similar or dissimilar) is described. The method allows simultaneous determination of the layer thickness, density, elastic moduli, and attenuation (longitudinal and shear) from normal and oblique incidence reflection (transmission) frequency spectra. Reflection (transmission) from the layer is represented as a function of six nondimensional parameters which are determined from the two experimentally measured spectra: one at normal and one at oblique incidence. The introduction of the set of nondimensional parameters allows one to transform the reconstruction process from one search in a six-dimensional space to two searches in three-dimensional spaces (one search for normal incidence and one for oblique). Thickness, density, and longitudinal and shear elastic moduli of the layer are calculated from the nondimensional parameters determined. The sensitivity of the method to individual properties and its stability against experimental noise are studied and the inversion algorithm is accordingly optimized. Experimental examples are given for a layer immersed in water and for a thermoplastic joint.
Acoustic, aerodynamic, physiologic, and perceptual properties of modal and vocal fry registers
Authors: Blomgren Michael , Chen Yang , Ng Manwa L. , Gilbert Harvey R.
Published: July 2002

The purpose of the study was to examine the acoustic, aerodynamic, physiologic, and perceptual characteristics of modal and vocal fry production. Twenty normal speakers (10 males, 10 females) participated in the study. Speech material included four sustained vowels (/i/, /ɑ/, /æ/, /u/), and syllable strings of /pi/ repetitions produced in both modal and vocal fry registers. Acoustic data (fundamental frequency, jitter, shimmer, and signal-to-noise ratio), aerodynamic data (airflow and air pressure), and electroglottographic (EGG) data were obtained simultaneously. Results demonstrated considerable differences across voice parameters for the modal and vocal fry registers. Fundamental frequency was significantly lower in vocal fry than in modal register for both males and females, however, significant gender differences existed only in modal register. For both males and females, measurements of jitter and shimmer were significantly higher and signal to noise ratio was significantly lower in vocal fry. In addition, airflow rate in modal register was almost three times as high as the airflow rate in vocal fry register during sustained vowel production. During syllable string production, subglottal air pressure values in modal register were approximately 1.5 times higher than that in the vocal fry register. In general, these data emphasize that the aeromechanical mechanisms of vocal fold vibratory behavior are substantially different between modal and vocal fry registers. A model of vocal fry phonation is presented to account for the present results.
Evidence for the distortion product frequency place as a source of distortion product otoacoustic emission (DPOAE) fine structure in humans. II. Fine structure for different shapes of cochlear hearing loss
Authors: Mauermann Manfred , Uppenkamp Stefan , van Hengel Peter W. J. , Kollmeier Birger
Published: July 2002

Distortion product otoacoustic emissions (DPOAE) were recorded from eight human subjects with mild to moderate cochlear hearing loss, using a frequency spacing of 48 primary pairs per octave and at a level L1=L2=60 dBSPL and with a fixed ratio f2/f1. Subjects with different shapes of hearing thresholds were selected. They included subjects with near-normal hearing within only a limited frequency range, subjects with a notch in the audiogram, and subjects with a mild to moderate high-frequency loss. If the primaries were located in a region of normal or near-normal hearing, but DP frequencies were located in a region of raised thresholds, the distortion product 2 f1–f2 was still observable, but the DP fine structure disappeared. If the DP frequencies fell into a region of normal thresholds, fine structure was preserved as long as DPOAE were generated, even in cases of mild hearing loss in the region of the primaries. These experimental results give further strong evidence that, in addition to the initial source in the primary region, there is a second source at the characteristic place of fDP. Simulations in a nonlinear and active computer model for DPOAE generation indicate different generation mechanisms for the two components. The disappearance of DPOAE fine structure might serve as a more sensitive indicator of hearing impairment than the consideration of DP level alone.
Auditory localization of nearby sources. III. Stimulus effects
Authors: Brungart Douglas S.
Published: July 2002

A series of experiments has examined the auditory localization of a nearby (<1 m) sound source under four conditions: (1) a fixed-amplitude condition where loudness-based distance cues were available; (2) a monaural condition where the contralateral ear was occluded by an ear-plug and muff; (3) a high-pass condition where the stimulus bandwidth was 3 Hz to 15 kHz; and (4) a low-pass condition where the stimulus bandwidth was 200 Hz to 3 kHz. The results of these experiments were compared to those of a previous experiment that measured localization performance for a nearby broadband, random-amplitude source [Brungart et al., J. Acoust. Soc. Am. 106, 1956–1968 (1999)]. Directional localization performance in each condition was consistent with the results of previous far-field localization experiments. Distance localization accuracy improved slightly in the fixed-amplitude condition relative to the earlier broadband random-amplitude experiment, especially near the median plane, but was severely degraded in the monaural condition. Distance accuracy was also found to be highly dependent on the low-frequency energy of the stimulus: in the low-pass condition, distance accuracy was similar to that in the broadband condition, while in the high-pass condition, distance accuracy was significantly reduced. The results suggest that low-frequency interaural level differences are the dominant auditory distance cue in the proximal region.
The Influence of Vacuole Formation on the Response and Failure of Filled Elastomers
Authors: Farris R. J.
Published: July 2002

A stochastic model has been developed that relates the stress-strain and the dilation-strain behavior of filled elastomers to the formation and growth of vacuoles which cause strain-induced volume dilatation in these materials. Both the cumulative and instantaneous frequencies of vacuole formation are simply derived from this model, thereby providing a method for determining the extent of microscopic failure within the material. Comparisons of the stress-strain and dilatation-strain relationships of various systems shows that the nonlinear stress-strain response is governed by these microscopic failures as are the strain capabilities. Hydrostatic pressure which normally has strong influence over the behavior of these materials is shown to be the result of suppressed vacuole formation.
Molecular orientation and instability in plane Poiseuille flow of a liquid-crystalline polymer
Authors: Bedford Bruce D. , Burghardt Wesley R.
Published: July 2002

A common rheological hypothesis, that the stress in a fluid element is only a function of its own deformation history, is rendered questionable in liquid-crystalline polymers (LCPs) due to the presence of distortional elasticity, through which neighboring fluid elements may directly influence one another. However, the fine defect texture in LCPs has led to the suggestion that fluid properties may be averaged over a mesoscopic length scale, intermediate between the molecular and macroscopic, so that averaged measures of fluid structure and stress at this scale depend only on their own deformation history [R. G. Larson and M. Doi, J. Rheol. 35, 539 (1991)]. We describe an experimental test of this hypothesis. If true, it should be possible to use rheological and rheo-optical data obtained in simple shear flow to predict the velocity and molecular orientation fields in a nonhomogeneous shear flow. Quantitative flow birefringence experiments are conducted on a liquid-crystalline solution of poly(benzyl glutamate), in plane Poiseuille flow. At low flow rates, the data support the local response hypothesis. As flow rate is increased, however, a profound instability occurs that is unanticipated based on behavior reported in homogeneous simple shear flow. The instability is characterized by large wavelength disturbances in structure oriented perpendicular to the flow direction that are clearly visible to the naked eye. With increasing flow rate, these structures decrease in size and become increasingly chaotic. Despite the onset of the instability, time-averaged measurements of average orientation may be qualitatively predicted based on simple shear flow data.
Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia
Authors: Yang Wenjian , Karol Seth E. , Hoshitsuki Keito , Lee Shawn , Larsen Eric C. , Winick Naomi , Carroll William L. , Loh Mignon L. , Raetz Elizabeth A. , Hunger Stephen P. , Winter Stuart S. , Dunsmore Kimberly P. , Devidas Meenakshi , Relling Mary V. , Yang Jun J.
Published: December 2022

Importance

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Hepatotoxic effects, including hyperbilirubinemia and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, are common during all phases of therapy and are linked to several chemotherapeutic agents, including asparaginase, mercaptopurine, and methotrexate.

Objective

To determine which genetic variants were associated with hyperbilirubinemia and elevated ALT and AST levels in children, adolescents, and young adults treated for ALL.

Design, Setting, and Participants

This retrospective analysis of a multiethnic genome-wide association study was conducted between January 1, 2019, and April 15, 2022, including patients treated as part of Children’s Oncology Group (COG) trials with centers in the United States, Canada, and Australia, which accrued data from December 29, 2003, to January 21, 2011 (AALL0232), and from January 22, 2007, to July 24, 2014 (AALL0434). Germline genotypes were interrogated using genome-wide arrays and imputed using a National Institutes of Health TOPMed Imputation server. Mixed-effects logistic regressions were used to account for multiple episodes for an individual patient. Genotype × treatment phase interaction was tested to uncover phase-specific genetic risk factors.

Exposures

Total duration of multiagent protocol chemotherapy ranging from 2.5 to 3.5 years.

Main Outcomes and Measures

The primary outcomes were National Cancer Institute Common Terminology Criteria for Adverse Events (version 4) hyperbilirubinemia of grade 3 or higher and elevated liver ALT and AST levels.

Results

A total of 3557 participants were included in the analysis (2179 [61.3%] male; median age, 11.1 [range, 1-30] years). Among 576 known variants associated with these liver function test results in the general population, UGT1A1 variant rs887829 and PNPLA3 variant rs738409 were associated with increased risk of hyperbilirubinemia (odds ratio [OR], 2.18 [95% CI, 1.89-2.53]; P = 6.7 × 10−27) and ALT and AST levels (OR, 1.27 [95% CI, 1.15-1.40]; P = 3.7 × 10−7), respectively, during treatment for ALL. Corresponding polygenic risk scores were associated with hepatotoxic effects across all therapy phases and were largely driven by UGT1A1 and PNPLA3 variants. Genome-wide association analysis revealed an age-specific variant near the CPT1A gene that was only associated with elevated ALT and AST levels among patients younger than 10 years (OR, 1.28 [95% CI, 1.18-1.39]; P = 8.7 × 10−10).

Conclusions and Relevance

These results suggest a strong genetic basis for interpatient variability in hyperbilirubinemia and aminotransferase level elevations during leukemia chemotherapy.
Gardeners' farmland in Komagome as seen in the “Ansei period Komagome Fuji shrine area map and illustration”
Authors: Watanabe Miki
Published: December 2022

In this study, we focused on contents described in the ‘Ansei period Komagome Fuji Shrine area map and illustration’. We verified the contents of the ‘Ansei period map’ and considered the aspects of gardeners' farmland in this area. Consequently, the following findings were obtained.

(1) Most of the farmers in this area also work as gardeners.

(2) A large number of farmers surnamed “Takagi,” “Utsumi,” and “Shimizu” already owned the lands in several distant places.

(3) From the address on the 1912 cadastral map, many locations matched the houses on the Ansei period map.
Compute in‐Memory with Non‐Volatile Elements for Neural Networks: A Review from a Co‐Design Perspective
Authors: Haensch Wilfried , Raghunathan Anand , Roy Kaushik , Chakrabarti Bhaswar , Phatak Charudatta M. , Wang Cheng , Guha Supratik
Published: December 2022

Deep learning has become ubiquitous, touching daily lives across the globe. Today, traditional computer architectures are stressed to their limits in efficiently executing the growing complexity of data and models. Compute‐in‐memory (CIM) can potentially play an important role in developing efficient hardware solutions that reduce data movement from compute‐unit to memory, known as the von Neumann bottleneck. At its heart is a cross‐bar architecture with nodal non‐volatile‐memory elements that performs an analog multiply‐and‐accumulate operation, enabling the matrix‐vector‐multiplications repeatedly used in all neural network workloads. The memory materials can significantly influence final system‐level characteristics and chip performance, including speed, power, and classification accuracy. With an over‐arching co‐design viewpoint, this review assesses the use of cross‐bar based CIM for neural networks, connecting the material properties and the associated design constraints and demands to application, architecture, and performance. Both digital and analog memory are considered, assessing the status for training and inference, and providing metrics for the collective set of properties non‐volatile memory materials will need to demonstrate for a successful CIM technology.
In‐Silico Device Performance Prediction of Cosensitizer Dye Pairs for Dye‐Sensitized Solar Cells
Authors: Devereux Leon R. , Vázquez‐Mayagoitia Álvaro , Sternberg Michael G. , Cole Jacqueline M.
Published: December 2022

Endeavors in the field of dye‐sensitized solar cells (DSCs) have shown great promise when adopting a data‐driven approach to materials discovery, such as successful molecular‐scale predictions of light‐harvesting chromophores. However, predictions of DSC dyes would become much more sophisticated if a molecular‐to‐macroscopic DSC device prediction methodology existed. Thereby, a fully computational pipeline is presented that predicts device‐performance parameters of DSCs which contain varying dye combinations. Optimal pairing of complementary dyes is identified via a data‐driven workflow that affords cosensitized DSCs with maximum power‐conversion efficiencies. Six high‐performing DSC dyes are paired with partner dyes that are screened from a database of 8488 compounds using sequential heuristic filters. Existing models that predict short‐circuit‐current density (JSC) and open‐circuit voltage (VOC) parameters are adapted to predict singly sensitized and cosensitized DSC performance. The predictions for Jsc values of singly sensitized devices match experimental literature values with comparable accuracy to more computationally costly methods. Five out of six dye pairings are predicted to have greater JSC values when cosensitized compared to their corresponding singly sensitized devices, including two pairs that show strong Jsc boosts of +13% and +12% when cosensitized. Thus, the prospect of an entirely in‐silico prediction pipeline for DSC performance that can be used to realize the fully automated design of optimized cosensitized DSCs is demonstrated.
Trends in obesity and severe obesity prevalence in the United States from 1999 to 2018
Authors: Fan Kexin , Lv Feifei , Li Huawei , Meng Fei , Wang Tao , Zhou Yunping
Published: December 2022

Background

The national obesity epidemic and trend of obesity prevalence have been characterized by a series of cross‐sectional surveys in the United States, however, less is known about obesity prevalence trajectory by birth cohort. This study aimed to investigate whether trends in obesity and severe obesity prevalence varied by birth cohorts among 1940s–1990s in the United States.

Methods

Using data from the National Health and Nutrition Examination Survey 1999–2018. The trends of obesity and severe obesity prevalence were conducted with synthetic birth cohort.

Results

There were 60 981 participants (weighted mean age, 38.1 years; female, 50.1%) assigned in 6 birth cohorts (1990s, 1980s, 1970s, 1960s, 1950s, and 1940s) over 1999–2018. The prevalence of obesity and severe obesity increased significantly with age during all birth cohorts except for the 1940s (Ptrend <0.001). For obesity, a significant positive quadratic trend was observed among 1990s birth cohort (Pnon‐linearity = 0.037), while a significant positive linear trend (Plinearity <0.001) among 1980s, 1970s, 1960s, and 1950s birth cohorts. Corresponding to same weighted mean age, the prevalence of both obesity and severe obesity in younger birth cohorts were much higher than the older birth generations.

Conclusions

The continued upward trend in obesity and severe obesity prevalence by birth cohort highlighted the need for continuing focus on surveillance of body mass index and identification, implementation, and evaluation of evidence‐based interventions to address this major health problem in the United States.
Regional variation in growth status: A cross‐sectional survey among Tibetan adolescents living at three different high altitudes in Tibet, China
Authors: Bi Cunjian , Lin Hongniu , Zhang Jie , Gui Xiaoying , Shi Zhen
Published: December 2022

Objective

To explore the regional and age variation in growth status and age‐by‐site interaction effect on the growth status among Chinese Tibetan adolescents at different altitudes in Tibet, China.

Methods

The research was conducted in three regions of Tibet, China: Nyingchi (average altitude 3100 m), Lhasa (average altitude 3650 m), and Nagqu (average altitude 4500 m). A total of 3817 Chinese Tibetan adolescents aged 12–18 years were tested for height, weight, chest circumference, and waist circumference. One‐way ANOVA was used to compare the growth status of Chinese Tibetan adolescents. Two‐way ANOVA was used to explore the age‐by‐site interaction effect on the growth status of Chinese Tibetan adolescents.

Results

The height, weight, and chest circumference of Chinese Tibetan adolescents in Nagqu are the lowest among the three cities. Age and site have an interaction effect influence on the growth status of Chinese Tibetan adolescents (p < .01).

Conclusions

The growth indicators (height, weight, chest circumference, WC) of Chinese Tibetan adolescents differed with altitudes. Policies to improve the growth status of Chinese Tibetan adolescents in Nagqu are urgently needed.