bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence rate of the time-domain Green’s function from the ambient noise cross-correlation function
Authors: Sabra Karim , Roux Philippe , Gerstoft Peter , Kuperman W. A.
Published: October 2013

It has been demonstrated experimentally and theoretically that an estimate of the Green’s function between two receivers can be obtained from the time derivative of the long-time average cross correlation of ambient noise between these two receivers. The emergence rate of these deterministic coherent arrival times of the cross-correlation function (i.e., the Green’s function estimate) from the recordings of an isotropic distribution of random noise sources is derived by evaluating the amplitude of the variance of the cross-correlation function. The knowledge of the emergence rate of NCF is essential for practical applications. To the first order, the variance is equal to the ratio of the product of the recorded energy by both receivers and the time–bandwidth product of the recordings. The variance of the time derivative of the correlation function is shown to have a similar dependency. These simple analytic formulas show a good agreement with the variance determined experimentally for the correlation of ocean ambient noise recorded in shallow water at a depth of 21 m, in the frequency band [300–530 Hz] for receiver separation up to 28 m and averaging time from 1 to 33 min.
Characteristics of bottom-roughness backscattering matrix in mode space
Authors: Wu Jinrong , Gao Tianfu , Shang Erchang
Published: October 2013

The bottom backscattering matrix of a normal-mode reverberation model describes the coupling relationship between the incident normal mode and scattering normal mode in the shallow-water waveguide. The numerical analysis of the bottom roughness backscattering matrix and the result of backscattering matrix inversion from experimental data were presented from mode space. The results show that: (1) at a close distance, the value of the backscattering matrix elements inclines toward high modes. The matrix is similar to a 2D high-pass filter; (2) at a middle distance, the value of the backscattering matrix elements inclines toward middle modes. The matrix is similar to a 2D bandpass filter; (3) at a far distance, the value of the backscattering matrix elements inclines toward low modes. The matrix is similar to a 2D low-pass filter. This phenomenon is caused by mode attenuation in the shallow-water waveguide. [Work supported by the NSFC.]
Talker sex mediates the influence of neighborhood density on vowel articulation
Authors: Munson Benjamin
Published: October 2013

Words with high phonological neighborhood densities (ND) are more difficult to perceive than words with low NDs [P. Luce and D. Pisoni (1998)]. Previous research has shown that the F1/F2 acoustic vowel space is larger for vowels in words with high ND relative to words with low NDs [B. Munson and N.P. Solomon (2004); R. Wright (2004)]. This may represent talkers’ tacit attempts to partially counter the perception difficulties associated with high-ND words. If so, then we would expect to see a larger effect of ND on vowel articulation in women, who have been observed to produce more intelligible speech than men, and to accommodate more to conversational partners than men [V. Hazan and D. Markham (2004); L. Namy et al. (2002)]. This hypothesis was tested by examining the influence of ND on vowel-space articulation by 22 women and 22 men. As expected, women produced overall more-dispersed vowel spaces than men, and vowel spaces associated with high-ND words were more-dispersed than low-ND words. Contrary to expectations, the influence of ND on vowel-space expansion was strongest in men. This appeared to be due a tendency for women not to produce contracted vowel spaces for low-ND words.
Tonal strength of harmonic complex tones in machinery noise
Authors: Lee Kyoung Hoon , Davies Patricia , Surprenant Aimee M.
Published: October 2013

The sounds of machines often contain families of harmonically related sine waves that are referred to as harmonic complex tones. The perceived tonal strength of these types of sounds can adversely influence people’s impressions of the sound. While a complex tone is comprised of many sine waves, usually only one prominent pitch sensation is produced. It can be argued that harmonic complex tones are perceived as a single entities, not as a sum of individual tones. A series of psychoacoustics tests was conducted to evaluate tonal prominence of harmonic complex tones. Two sounds of equal loudness were played to subjects. One was a harmonic complex tone in noise and the other was a single tone in noise. Subjects were asked to equalize the perceived tonalness of the two sounds by adjusting the tone to noise ratio of the single tone in noise. Tonalness and Terhardt’s pitch perception models were applied to the pairs of sounds used in each test. The feasibility of replacing harmonic complex tones with a tonally equivalent simple sound was investigated, and strong correlations between Aures’ tonality for the simple and complex tones were found.
Laryngeal adjustments for devoicing of /h/: A within-speaker study
Authors: Koenig Laura
Published: October 2013

Past work has investigated cross-speaker and cross-gender differences in voicing of /h/ in English speakers. The purpose of this study was to see whether a phonetically sophisticated speaker could intentionally alter his /h/ voicing patterns, and, if so, how he would effect any changes. One adult male speaker of American English, a trained phonetician and dialectologist, produced approximately 500 repetitions of intervocalic /h/ in short carrier phrases, with differing vowel contexts and loudness levels. In the first block, the speaker produced the utterances normally (i.e., without specific instructions on /h/ production); in the second, he was explicitly asked to devoice his /h/’s. Results indicated that the incidence of devoiced /h/ increased from 2% in the first block to 69% in the second block. On average, the /h/’s in the second block were produced with higher baseline airflows, indicating more extreme laryngeal abduction. This alone did not account for the speaker’s devoicing behavior, however, since the soft condition, which had the lowest peak airflows in the second block, had the most devoicing. Voice source measures will be compared between the two blocks to clarify how the speaker altered his laryngeal setting to achieve more devoicing. [Work supported by NIH.]
Overview of noise policy in California
Authors: Phillips James
Published: October 2013

This paper provides a general review of noise policy in California including general plan noise elements, municipal code noise ordinances, and the California Building Code of Regulations Title 24. The challenges that an acoustical consultant faces while trying to meet the requirements or, as is often the case, trying to achieve the intent of such policies, will be discussed. What works or doesn’t work?
Development of an acoustical energy harvester
Authors: Horowitz Stephen B. , Nishida Toshikazu , Cattafesta Louis N. , Sheplak Mark
Published: October 2013

This paper presents the development of one component of a miniature acoustical energy harvesting system that is designed to convert acoustical energy into electrical energy. This component consists of a composite circular membrane containing a circular piezoelectric ring near the clamped boundary. An acoustic pressure fluctuation leads to a deflection of the membrane. This deflection generates a strain concentrated near the clamped boundary. The piezoelectric material, strategically placed in this region of high strain, converts the strain into an electrical voltage that can then be utilized in an electrical circuit or stored in a battery. The energy harvester was designed by combining a linear piezoelectric composite plate model with a lumped-element, electroacoustic model. Characterization was performed via acoustic excitation in a plane-wave tube. Preliminary results indicate a maximum generated output voltage of 18.2 mV across a 78.3−kΩ resistive load, resulting in 4.2 μW of generated power for an incident sound pressure level of 153.4 dB.
A scattering analysis of echoes due to biosonar signals emitted by foraging beaked whales
Authors: Jones Benjamin A. , Stanton Timothy K. , Lavery Andone C. , Johnson Mark P. , Madsen Peter T. , Tyack Peter L.
Published: October 2013

Blainville’s beaked whales (Mesoplodon densirostris) hunt their prey by echolocation at depths of more than 500 meters. These whales use a FM upswept, ultrasonic click, of greater than an octave bandwidth to search for, localize, and close on individual prey which generally consist of mesopelagic fishes and squid. It is well known that acoustic scattering from organisms of varying morphology (e.g., swimbladder-bearing or fluidlike) is strongly frequency dependent. However, it is unknown if the broadband nature of the whales’ outgoing signal, and the frequency dependence of the echoes, is a key component in the classification and selection of their prey. Non-invasive, acoustic ‘‘Dtags,’’ which sample stereo acoustic data at a rate which satisfies the high-frequency Nyquist criterion for the animal’s transmit signal, were affixed to beaked whales. The Dtags successfully recorded transmitted signals and associated echoes. Structure was observed in the frequency content of echoes from isolated targets in the water column which may be used for classification by the whales. An analysis of the echoes identified as possibly due to prey has demonstrated that multiple classes of frequency responses are present. These results will be compared with the frequency responses of possible prey types.
Strategies for weighting exposure in the development of acoustic criteria for marine mammals
Authors: Miller James H. , Bowles Anne E. , Gentry Roger L. , Ellison William T. , Finneran James J. , Greene Jr. Charles R. , Kastak David , Ketten Darlene R. , Tyack Peter L. , Nachtigall Paul E. , Richardson W. John , Thomas Jeanette A.
Published: October 2013

The Noise Exposure Criteria Group has been developing noise exposure criteria for marine mammals. Although the primary focus of the effort is development of criteria to prevent injury, the Group has also emphasized the development of exposure metrics that can be used to predict injury with accuracy and precision. Noise exposure metrics for humans have proven to be more effective when they account for psychophysical properties of the auditory system, particularly loudness perception. Usually noise is filtered using the A-weighting function, an idealized curve based on the human 40-phon equal loudness function. However, there are no empirical studies to show whether a comparable procedure for animals will improve predictions. The Noise Exposure Criteria Group panel has proposed to weight noise data by functions that admit sound throughout the frequency range of hearing in five marine mammal groupings—low frequency cetaceans (mysticetes), midfrequency cetaceans, high-frequency cetaceans, pinnipeds in air, and pinnipeds in water. The algorithm for the functions depends only on the upper and lower frequency limits of hearing and does not differentially weight frequencies based on sensitivity within the range. This procedure is considered conservative. However, if the human case may be taken as a model, it is not likely to produce precise predictions. Empirical data are essential to finding better estimators of exposure.
Foraging behavior of fish-eating sperm whales in the Gulf of Alaska in the presence and absence of fishing vessels
Authors: Thode Aaron , Straley Jan , Folkert Kendall , O’Connell Victoria , Tiemann Christopher
Published: October 2013

Historical whaling records indicate that sperm whales off southeast Alaska incorporate fish into their diets, particularly black cod (Anoploploma fimbria). Since 1995 this fact has become relevant to fisheries’ concerns in the form of increased depredation encounters between longline fishermen and over 40 sperm whales. Since 2002 the SE Alaska Sperm Whale Avoidance Project (SEASWAP) has been studying this phenomenon using fishermen reports, photo-ID, biopsy, and (since 2004) passive acoustics using both towed arrays and autonomous recorders placed on longline deployments. By using acoustic multipath the range and depths of foraging whales can be determined. Findings to date indicate that, under natural conditions, sperm whales are foraging at mid-depth in the water column (e.g., 250 m in 500-m-deep water), and that their dive cycle durations are similar to those reported in other oceans. This information is being compared with depth measurements of black cod at various stages of their life cycle. There is increasing evidence that distinctive acoustic cues made by longline vessels lead to changes in diving and acoustic behavior by the animals, when the animals are less than 10 nautical miles away. [Work supported by the North Pacific Research Board.]
Computer simulation of three-dimensional directional response measurements
Authors: Warren Daniel M.
Published: October 2013

Early in the development of methods for measuring the three-dimensional directional response of hearing aids, there were many questions on how to distribute sound sources over the sphere. The method had to be accurate, yet practical to implement. Decisions on the scheme for distributing sound sources, the density of sound sources, and the weighting of results from each source have impact on accuracy. A simulation of the directional response of an array of microphones in the direct and scattered acoustic field near a rigid sphere was created and used to evaluate various means of distributing sound sources.
Evaluating gestural overlap as an influence on perception of fricative-stop clusters
Authors: Choi Susie , Byrd Dani
Published: October 2013

This study investigates the effect of intergestural timing and prosodic context on perception. The articulation and perception of word-edge /sk/ and /sp/ clusters in words preceding or following various prosodic boundaries are considered. Excised acoustic recordings of these words provided stimuli for a perception experiment in which listeners did a phoneme-monitoring task, listening for [s]. Using magnetometer data, articulatory overlap of the two consonants was measured. Listener reaction times were evaluated to determine whether the overlap measure and/or the prosodic category in which the cluster occurred had an influence on the speed of response. This presentation will focus on the onset clusters. Results show: (1) reaction times for /s/-monitoring differed according to phrasal position, such that cluster stimuli following larger prosodic boundaries have longer RTs; (2) responses are significantly faster when clusters have greater articulatory overlap; and (3) intergestural overlap is more important in capturing response variability than phrasal category. Similar studies examining stop clusters [Byrd, Phonetica (1992); Goldstein and Suprenant, J. Acoust. Soc. Am. 104, 518 (1998)] have found that overlap among stops can cause perceived deletion; the study suggests listeners utilize the information encoded by increased overlap when the overlapped segments aerodynamics allows preservation, rather than loss, of information. [Work supported by NIH.]
Lexical and context effects in children’s audiovisual speech recognition
Authors: Holt Rachael , Kirk Karen , Pisoni David , Burckhartzmeyer Lisa , Lin Anna
Published: October 2013

The Audiovisual Lexical Neighborhood Sentence Test (AVLNST), a new, recorded speech recognition test for children with sensory aids, was administered in multiple presentation modalities to children with normal hearing and vision. Each sentence consists of three key words whose lexical difficulty is controlled according to the Neighborhood Activation Model (NAM) of spoken word recognition. According to NAM, the recognition of spoken words is influenced by two lexical factors: the frequency of occurrence of individual words in a language, and how phonemically similar the target word is to other words in the listeners lexicon. These predictions are based on auditory similarity only, and thus do not take into account how visual information can influence the perception of speech. Data from the AVLNST, together with those from recorded audiovisual versions of isolated word recognition measures, the Lexical Neighborhood, and the Multisyllabic Lexical Neighborhood Tests, were used to examine the influence of visual information on speech perception in children. Further, the influence of top-down processing on speech recognition was examined by evaluating performance on the recognition of words in isolation versus words in sentences. [Work supported by the American Speech-Language-Hearing Foundation, the American Hearing Research Foundation, and the NIDCD, T32 DC00012 to Indiana University.]
Methodological considerations of acoustic playbacks to test the behavioral significance of call directionality in male northern elephant seals (Mirounga angustirostris)
Authors: Holt Marla M. , Insley Stephen J. , Southall Brandon L. , Schusterman Ronald J.
Published: October 2013

While attempting to gain access to receptive females, male northern elephant seals form dominance hierarchies through multiple dyadic interactions involving visual and acoustic signals. These signals are both highly stereotyped and directional. Previous behavioral observations suggested that males attend to the directional cues of these signals. We used in situ vocal playbacks to test whether males attend to directional cues of the acoustic components of a competitors calls (i.e., variation in call spectra and source levels). Here, we will focus on playback methodology. Playback calls were multiple exemplars of a marked dominant male from an isolated area, recorded with a directional microphone and DAT recorder and edited into a natural sequence that controlled call amplitude. Control calls were recordings of ambient rookery sounds with the male calls removed. Subjects were 20 marked males (10 adults and 10 subadults) all located at Año Nuevo, CA. Playback presentations, calibrated for sound-pressure level, were broadcast at a distance of 7 m from each subject. Most responses were classified into the following categories: visual orientation, postural change, calling, movement toward or away from the loudspeaker, and re-directed aggression. We also investigated developmental, hierarchical, and ambient noise variables that were thought to influence male behavior.
Noise modeling, noise experiment, and noise inversion
Authors: Harrison Chris H.
Published: October 2013

Recent developments in inverting ambient noise to obtain bottom reflection properties originated from an understanding of noise behavior and from noise modeling. Sea-surface noise can be modeled equivalently as a ray, wave, or mode phenomenon, but often the ray or flux approach provides the most insight (explaining, e.g., the noise-notch or low-frequency noise enhancement). Theoretically, noise vertical directionality is surprisingly sensitive to the effective depth of the sheet of sound sources, and this is borne out in the spread of behaviors found experimentally. A number of noise inversion approaches have been proposed based on coherence or directionality of sea-surface noise, individual ships or shipping, and airplane doppler. Using a drifting vertical array as a means to measure directionality, one can infer reflection coefficient versus angle and frequency. One can then use this directly for propagation calculation, or alternatively invert to geoacoustic parameters with the help of a fast noise model. A further development is to recover the reflection phase using spectral factorization, then Fourier transform to get the impulse response, which becomes a sub-bottom profile for a drifting array. At 4-kHz design frequency, the layer structure thus determined compares well with a boomer down to 15 m.
Evaluation of diffuse reflections in a 1:10 scale model hall
Authors: Jeon Jin Yong , Ryu Jong Kwan , Kim Yong Hee
Published: October 2013

The acoustical properties of a multipurpose hall (opera mode) were measured in a 1:10 scale model to investigate the effect of diffuse reflections. Measurements were made in stall areas with and without diffusers on the walls adjacent to the pit and on the side walls. The diffusers consisted of 15- to 25-cm-high hemispheres and 25-cm high polygons. A mix of these diffusers was used to cover about 40% of the area of the side walls. It was found that 1-IACCE3 increased at positions close to the walls adjacent to the pit and the first reflection with maximum amplitude increased in some seats. The possibility of diffuse reflections either hitting the proscenium wall or soffit close to the side wall first, as well as reflections coming from both sides of the hall explains the reason for the bunch of early reflections in the impulse responses. The effect of diffusers at each receiver position was investigated via subjective evaluation. The results from the subjective evaluation indicated that diffuse reflections were preferred to specular reflections.
Production and perception of whispered vowels
Authors: Kiefte Michael
Published: October 2013

Information normally associated with pitch, such as intonation, can still be conveyed in whispered speech despite the absence of voicing. For example, it is possible to whisper the question ‘‘You are going today?’’ without any syntactic information to distinguish this sentence from a simple declarative. It has been shown that pitch change in whispered speech is correlated with the simultaneous raising or lowering of several formants [e.g., M. Kiefte, J. Acoust. Soc. Am. 116, 2546 (2004)]. However, spectral peak frequencies associated with formants have been identified as important correlates to vowel identity. Spectral peak frequencies may serve two roles in the perception of whispered speech: to indicate both vowel identity and intended pitch. Data will be presented to examine the relative importance of several acoustic properties including spectral peak frequencies and spectral shape parameters in both the production and perception of whispered vowels. Speakers were asked to phonate and whisper vowels at three different pitches across a range of roughly a musical fifth. It will be shown that relative spectral change is preserved within vowels across intended pitches in whispered speech. In addition, several models of vowel identification by listeners will be presented. [Work supported by SSHRC.]
Axisymmetric acoustic scattering from submerged prolate spheroidal shells
Authors: Boisvert Jeffrey E. , Hayek Sabih I.
Published: October 2013

The equations of motion for nonaxisymmetric vibration of prolate spheroidal shells of constant thickness were derived using Hamilton’s principle [S. I. Hayek and J. E. Boisvert, J. Acoust. Soc. Am. 114, 2799–2811 (2003)]. The shell theory used in this derivation includes shear deformations and rotatory inertias. The shell displacements and rotations were expanded in infinite series of comparison functions. These include associated Legendre functions in terms of the prolate spheroidal angular coordinate and circular functions in the azimuthal angle coordinate. The shell is insonified by a plane wave incident along the major axis. The external (heavy) fluid loading impedance was computed using an eigenfunction expansion of prolate spheroidal wavefunctions. Far-field scattered acoustic pressure spectra are presented for several shell thickness-to-half-length ratios ranging from 0.005 to 0.1, and for various shape parameters, a, ranging from an elongated spheroidal shell (a=1.01) to a spherical shell (a∼100). The far-field directivity of acoustic scattering is presented at selected frequencies. [Work supported by the ONR/ASEE Summer Faculty Research Program.]
Application of adaptive beamforming to geoacoustic inversion and source localization
Authors: Stotts Steven , Hawkins Brian
Published: October 2013

Utilizing sources of opportunity to perform simultaneous geoacoustic inversion and localization has been established using conventional beamforming (CBF) applied to data from subapertures of a bottom-mounted horizontal line array. [R. A. Koch and D. P. Knobles, ‘‘Geoacoustic inversion with ships as sources,’’ J. Acoust. Soc. Am. 117, 626–637 (2005)] Often, multiple sources may coexist within a field, and isolating a single source is desirable prior to performing inversions. Spatial filtering has been shown to improve localizations by focusing on bearing regions containing the source of interest. [S. A. Stotts, ‘‘A robust spatial filtering technique for multisource localization and geoacoustic inversion,’’ J. Acoust. Soc. Am. 117, 139–162 (2005)]. Adaptive beamforming (ABF) is an alternative approach used to suppress noise and increase the signal-to-noise ratio for sources of interest. Comparisons between previous CBF inversion results and ABF inversions applied to a known data set will be presented. The inversion algorithm uses simulated annealing with a cost function correlating cross-spectral data from the subapertures with modeled cross spectra.
The effects of speechreading training on viseme categories for vowels
Authors: Richie Carolyn
Published: October 2013

The status of visemes, groups of visually confusable speech sounds, for American English vowels has been disputed for some time. While some researchers claim that vowels are visually distinguishable, others claim that some vowels are visually confusable and comprise viseme categories. Data from our study on speechreading words and sentences were examined for evidence of vowel visemes [C. Richie and D. Kewley-Port, J. Acoust. Soc. Am. 117, 2570 (2005)]. Normal-hearing listeners were tested in auditory-visual conditions in masking noise designed to simulate a hearing loss. They were trained on speechreading tasks emphasizing vowels, consonants, or vowels and consonants combined. Pre- and post-training speechreading tests included identification of 10 vowels in CVC context. Pre-training data (vowel-identification confusion matrices) were used to determine whether vowel visemes exist for untrained speechreaders. Post-training results were examined to determine whether the number of vowel response categories increased and whether the number of vowel identification errors decreased, for trained versus untrained participants. The impact of these training programs on speechreading performance is discussed in terms of vowel visemes. [Work supported by NIHDCD02229.]
Common modes of vocal tract articulation for vowels
Authors: Story Brad
Published: October 2013

The purpose of this study was to investigate the spatial similarity of vocal tract shaping patterns across speakers and the similarity of their acoustic effects. Vocal tract area functions for eleven American English vowels were first obtained from six speakers, three female and three male, using magnetic resonance imaging (MRI). Each speaker’s set of area functions was then decomposed into mean area vectors and representative modes (eigenvectors) using principal components analysis (PCA). Three modes accounted for more than 90% of the variance in the original data sets for each speaker. The general shapes of the first two modes were found to be highly correlated across all six speakers. To demonstrate the acoustic effects the modes, both isolated and combined, a mapping between the mode scaling coefficients and [F1,F2] pairs was generated for each speaker. The mappings were unique for all six speakers in terms of the exact shape of the [F1,F2] vowel space, but the general effect of the modes was the same in each case. The results tend to support the idea that the modes provide a common system for perturbing a unique underlying neutral vocal tract shape. [Work supported by NIH R01-DC04789.]
Voltage-Gated Sodium Channel in Grasshopper Mice Defends Against Bark Scorpion Toxin
Authors: Rowe Ashlee H. , Xiao Yucheng , Rowe Matthew P. , Cummins Theodore R. , Zakon Harold H.
Published: October 2013

Bite Me!

As unpleasant as it is, pain serves a purpose, to alert the body to potential damage. This protective function may explain why few predators have evolved resistance to the painful venoms used as a defense by their prey. The grasshopper mouse, however, is insensitive to one of the most painful stings in the animal kingdom—that of the bark scorpion.

Rowe
et al.

(p.
441
; see the Perspective by

Lewin

) now show that grasshopper mice use the toxins present in the scorpion venom to block voltage-gated pain transmission, temporarily reducing their sensitivity to nonvenom-induced pain. Thus, grasshopper mice use the scorpion's painful defense to their advantage and have evolved a mechanism that allows for reduction of pain sensitivity only when it is needed.
Biodiversity Risks from Fossil Fuel Extraction
Authors: Butt N. , Beyer H. L. , Bennett J. R. , Biggs D. , Maggini R. , Mills M. , Renwick A. R. , Seabrook L. M. , Possingham H. P.
Published: October 2013

The overlapping of biodiverse areas and fossil fuel reserves indicates high-risk regions.
Fine Tuning of Craniofacial Morphology by Distant-Acting Enhancers
Authors: Attanasio Catia , Nord Alex S. , Zhu Yiwen , Blow Matthew J. , Li Zirong , Liberton Denise K. , Morrison Harris , Plajzer-Frick Ingrid , Holt Amy , Hosseini Roya , Phouanenavong Sengthavy , Akiyama Jennifer A. , Shoukry Malak , Afzal Veena , Rubin Edward M. , FitzPatrick David R. , Ren Bing , Hallgrímsson Benedikt , Pennacchio Len A. , Visel Axel
Published: October 2013

Introduction

The shape of the face is one of the most distinctive features among humans, and differences in facial morphology have substantial implications in areas such as social interaction, psychology, forensics, and clinical genetics. Craniofacial shape is highly heritable, including the normal spectrum of morphological variation as well as susceptibility to major craniofacial birth defects. In this study, we explored the role of transcriptional enhancers in the development of the craniofacial complex. Our study is based on the rationale that such enhancers, which can be hundreds of kilobases away from their target genes, regulate the spatial patterns, levels, and timing of gene expression in normal development. 

Methods

To identify distant-acting enhancers active during craniofacial development, we used chromatin immunoprecipitation on embryonic mouse face tissue followed by sequencing to identify noncoding genome regions bound by the enhancer-associated p300 protein. We used LacZ reporter assays in transgenic mice and optical projection tomography (OPT) to determine three-dimensional expression patterns of a subset of these candidate enhancers. Last, we deleted three of the craniofacial enhancers from the mouse genome to assess their effect on gene expression and craniofacial morphology during development.

Results

We identified more than 4000 candidate enhancer sequences predicted to be active in the developing craniofacial complex. The majority of these sequences are at least partially conserved between humans and mice, and many are located in chromosomal regions associated with normal facial morphology or craniofacial birth defects. Characterization of more than 200 candidate enhancer sequences in transgenic mice revealed a remarkable spatial complexity of in vivo expression patterns. Targeted deletions of three craniofacial enhancers near genes with known roles in craniofacial development resulted in changes of expression of those genes as well as quantitatively subtle but definable alterations of craniofacial shape. 

Discussion

Our analysis identifies enhancers that fine tune expression of genes during craniofacial development in mice. These results support that variation in the sequence or copy number of craniofacial enhancers may contribute to the spectrum of facial variation we find in human populations. Because many craniofacial enhancers are located in genome regions associated with craniofacial birth defects, such as clefts of the lip and palate, our results also offer a starting point for exploring the contribution of noncoding sequences to these disorders.
A Radical Intermediate in Tyrosine Scission to the CO and CN
−
Ligands of FeFe Hydrogenase
Authors: Kuchenreuther Jon M. , Myers William K. , Stich Troy A. , George Simon J. , NejatyJahromy Yaser , Swartz James R. , Britt R. David
Published: October 2013

Piecing Together Hydrogenase

Microbial hydrogenase enzymes generally use iron to catalyze the reversible formation of hydrogen from protons and electrons. Key to their efficiency is a set of iron-coordinating ligands, including CO and cyanide.

Kuchenreuther
et al.

(p.
472
) examined how the HydG maturase enzyme breaks down the amino acid tyrosine to derive these diatomic ligands for assembly of the diiron class of hydrogenases. The first step involves abstraction of an H atom from the phenolic OH substituent of the side chain. Electron paramagnetic resonance spectroscopy revealed a radical intermediate that subsequently results from heterolysis of the bond tethering the side chain to the α-carbon. With the side chain thus jettisoned, the residual dehydroglycine could be transformed into CO and CN
−
.
Stabilizing Liquid Drops in Nonequilibrium Shapes by the Interfacial Jamming of Nanoparticles
Authors: Cui Mengmeng , Emrick Todd , Russell Thomas P.
Published: October 2013

Dynamic Surfactants

Surfactants are used to form a stable interface between two nonmiscible liquids, like oil and water, so that droplets of one fluid can be entrained in the other.

Cui
et al.

(p.
460
) designed a surfactant based on the association of a hydrophilic nanoparticle with a functionalized oleophilic molecule that self-assembles at a water-oil interface to produce a composite surfactant. Once adsorbed, the nanoparticles tend to remain in place causing them to accumulate and “jam” at the interface. When a drop was deformed, more surfactant could assemble at the surface, allowing droplets of various shapes to be produced.
The New Core Paradox
Authors: Olson Peter
Published: October 2013

Recent results show that Earth's core has a large thermal conductivity, raising questions over how the geodynamo evolved.
Expanding the Scope of Fluorine Tags for PET Imaging
Authors: Zhu Lin , Ploessl Karl , Kung Hank F.
Published: October 2013

A fast fluorination method can allow a wider range of drug molecules to be imaged in the body with positron emission tomography (PET).
Mucus Coat, a Dress Code for Tolerance
Authors: Belkaid Yasmine , Grainger John
Published: October 2013

Mucus is a determinant of gut immune specification and immune tolerance.

[Also see Research Article by

Shan
et al.

]
Surprising New Dengue Virus Throws a Spanner in Disease Control Efforts
Authors: Normile Dennis
Published: October 2013

Scientists have discovered a fifth dengue virus. The first new serotype discovered in a half century could complicate control efforts, especially the quest for a vaccine.
Significant Reduction in Rate of Indeterminate Results of the QuantiFERON-TB Gold In-Tube Test by Shortening Incubation Delay
Authors: Yun Jae Won , Chung Hae-Sun , Koh Won-Jung , Chung Doo Ryeon , Kim Yae-Jean , Kang Eun-Suk
Published: October 2013

The QuantiFERON-TB Gold In-Tube (QFT-G IT) test (Cellestis Inc., Valencia, CA) is one of the gamma interferon release assays (IGRAs) that are promising tools for diagnosing active or latent
Mycobacterium tuberculosis
infections. We investigated the clinical and laboratory factors that affect the rate of indeterminate QFT-G IT test results. We also suggest a workflow strategy for achieving optimized test results using the QFT-G IT test for the diagnosis of active tuberculosis (TB) or latent TB infection. We performed statistical analysis using data from a retrospective review of medical records. The first phase included 683 QFT-G IT test results from 676 patients tested between January 2008 and May 2008, and the second phase included an additional 663 QFT-G IT test results from 653 patients tested between January 2008 and December 2008 at Samsung Medical Center, a tertiary care hospital in South Korea. Immunosuppressive drug therapy, underlying diseases, bedridden status, and hypoalbuminemia were significantly associated with indeterminate QFT-G IT test results. With reduction of the incubation delay during the test procedure from an average of 9.82 h to an average of 2.70 h with changes in the workflow, the frequency of indeterminate QFT-G IT test results was significantly reduced from 11.4% to 2.7%. With >6 h of incubation delay, however, the frequency of indeterminate QFT-G IT test results was increased in a statistically significant manner. This study demonstrates that not only clinicopathological factors but also laboratory factors, such as incubation delay, significantly affect the rate of indeterminate QFT-G IT test results; therefore, optimization of the test procedure may contribute to reductions in the rate of indeterminate QFT-G IT test results, which delay the diagnosis of TB.
Rapid Identification and Subtyping of Helicobacter cinaedi Strains by Intact-Cell Mass Spectrometry Profiling with the Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Taniguchi Takako , Sekiya Ayumi , Higa Mariko , Saeki Yuji , Umeki Kazumi , Okayama Akihiko , Hayashi Tetsuya , Misawa Naoaki
Published: October 2013

Helicobacter cinaedi
infection is recognized as an increasingly important emerging disease in humans. Although
H. cinaedi
-like strains have been isolated from a variety of animals, it is difficult to identify particular isolates due to their unusual phenotypic profiles and the limited number of biochemical tests for detecting helicobacters. Moreover, analyses of the 16S rRNA gene sequences are also limited due to the high levels of similarity among closely related helicobacters. This study was conducted to evaluate intact-cell mass spectrometry (ICMS) profiling using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) as a tool for the identification of
H. cinaedi
. A total of 68 strains of
H. cinaedi
isolated from humans, dogs, a cat, and hamsters were examined in addition to other
Helicobacter
species. The major ICMS profiles of
H. cinaedi
were identical and differed from those of
Helicobacter bilis
, which show >98% sequence similarity at the 16S rRNA sequence level. A phyloproteomic analysis of the
H. cinaedi
strains examined in this work revealed that human isolates formed a single cluster that was distinct from that of the animal isolates, with the exception of two strains from dogs. These phyloproteomic results agreed with those of the phylogenetic analysis based on the nucleotide sequences of the
hsp60
gene. Because they formed a distinct cluster in both analyses, our data suggest that animal strains may not be a major source of infection in humans. In conclusion, the ICMS profiles obtained using a MALDI-TOF MS approach may be useful for the identification and subtyping of
H. cinaedi
.
Real-Time Reverse Transcription-PCR Assay Panel for Middle East Respiratory Syndrome Coronavirus
Authors: Lu Xiaoyan , Whitaker Brett , Sakthivel Senthil Kumar K. , Kamili Shifaq , Rose Laura E. , Lowe Luis , Mohareb Emad , Elassal Emad M. , Al-sanouri Tarek , Haddadin Aktham , Erdman Dean D.
Published: October 2013

A new human coronavirus (CoV), subsequently named Middle East respiratory syndrome (MERS)-CoV, was first reported in Saudi Arabia in September 2012. In response, we developed two real-time reverse transcription-PCR (rRT-PCR) assays targeting the MERS-CoV nucleocapsid (N) gene and evaluated these assays as a panel with a previously published assay targeting the region upstream of the MERS-CoV envelope gene (upE) for the detection and confirmation of MERS-CoV infection. All assays detected ≤10 copies/reaction of quantified RNA transcripts, with a linear dynamic range of 8 log units and 1.3 × 10
−3
50% tissue culture infective doses (TCID
50
)/ml of cultured MERS-CoV per reaction. All assays performed comparably with respiratory, serum, and stool specimens spiked with cultured virus. No false-positive amplifications were obtained with other human coronaviruses or common respiratory viral pathogens or with 336 diverse clinical specimens from non-MERS-CoV cases; specimens from two confirmed MERS-CoV cases were positive with all assay signatures. In June 2012, the U.S. Food and Drug Administration authorized emergency use of the rRT-PCR assay panel as an
in vitro
diagnostic test for MERS-CoV. A kit consisting of the three assay signatures and a positive control was assembled and distributed to public health laboratories in the United States and internationally to support MERS-CoV surveillance and public health responses.
Human T-Cell Leukemia/Lymphoma Virus Type 1 p30, but Not p12/p8, Counteracts Toll-Like Receptor 3 (TLR3) and TLR4 Signaling in Human Monocytes and Dendritic Cells
Authors: Fenizia Claudio , Fiocchi Martina , Jones Kathryn , Parks Robyn Washington , Ceribelli Michele , Chevalier Sebastien A. , Edwards Dustin , Ruscetti Francis , Pise-Masison Cynthia A. , Franchini Genoveffa
Published: October 2013

The human T-cell leukemia/lymphoma virus type 1 (HTLV-1) p30 protein, essential for virus infectivity
in vivo
, is required for efficient infection of human dendritic cells (DCs) but not B and T cells
in vitro
. We used a human monocytic cell line, THP-1, and dendritic cells to study the mechanism of p30 and p12/p8 requirements in these cell types. p30 inhibited the expression of interferon (IFN)-responsive genes (ISG) following stimulation by lipopolysaccharide (LPS) of Toll-like receptor 4 (TLR4) and by poly(I·C) of TLR3 but not of TLR7/8 with imiquimod. Results with THP-1 mirrored those for
ex vivo
human primary monocytes and monocyte-derived dendritic cells (Mo-mDC). The effect of p30 on TLR signaling was also demonstrated by ablating its expression within a molecular clone of HTLV-1. HTLV-1 infection of monocytes inhibited TLR3- and TLR4-induced ISG expression by 50 to 90% depending on the genes, whereas the isogenic clone p30 knockout virus was less effective at inhibiting TLR3 and TRL4 signaling and displayed lower infectivity. Viral expression and inhibition of ISG transcription was, however, rescued by restoration of p30 expression. A chromatin immunoprecipitation assay demonstrated that p30 inhibits initiation and elongation of PU.1-dependent transcription of IFN-α1, IFN-β, and TLR4 genes upon TLR stimulation. In contrast, experiments conducted with p12/p8 did not demonstrate an effect on ISG expression. These results provide a mechanistic explanation of the requirement of p30 for HTLV-1 infectivity
in vivo
, suggest that dampening interferon responses in monocytes and DCs is specific for p30, and represent an essential early step for permissive HTLV-1 infection and persistence.
Host Restriction of Influenza Virus Polymerase Activity by PB2 627E Is Diminished on Short Viral Templates in a Nucleoprotein-Independent Manner
Authors: Paterson Duncan , te Velthuis Aartjan J. W. , Vreede Frank T. , Fodor Ervin
Published: October 2013

Most avian influenza viruses do not replicate efficiently in human cells. This is partly due to the low activity of the RNA polymerase of avian influenza viruses in mammalian cells. Nevertheless, this impediment can be overcome through an E→K adaptive mutation at residue 627 of the PB2 subunit of the polymerase. Accordingly, viral ribonucleoprotein (RNP) reconstitution assays show that a viral polymerase containing PB2 627E has impaired activity in mammalian cells compared to a viral polymerase that contains PB2 627K, characteristic of mammalian-adapted influenza viruses. In contrast, purified viral polymerases containing either PB2 627E or PB2 627K show comparable levels of activity in transcription assays that require no RNP assembly. We sought to reconcile these conflicting observations by using an NP-independent cell-based transcription/replication assay to assess viral polymerase activity. We found that PB2 627E polymerase restriction in mammalian cells is independent of NP expression but is dependent on the length of the viral RNA template. In addition, restriction of PB2 627E polymerase was overcome by mutations specific to the viral RNA template promoter sequence. Consequently, we propose that PB2 627E affects recruitment of the viral RNA promoter by the viral polymerase in mammalian cells.
Varicella-Zoster Virus ORF49 Functions in the Efficient Production of Progeny Virus through Its Interaction with Essential Tegument Protein ORF44
Authors: Sadaoka Tomohiko , Serada Satoshi , Kato Junko , Hayashi Mayuko , Gomi Yasuyuki , Naka Tetsuji , Yamanishi Koichi , Mori Yasuko
Published: October 2013

The ORF49 tegument protein of varicella-zoster virus (VZV) is one of the core gene products that is conserved among herpesvirus family members. Although ORF49 is known to be a cell-tropic factor, its detailed functions remain elusive. ORF44 is another core gene product reported to be essential, although its characterization and detailed functional analysis have not been reported. These two core gene products form a complex in other herpesviruses beyond the host species and herpesvirus subfamilies. Here, we show that complex formation between ORF44 and ORF49 is conserved in VZV. We serendipitously found that binding is eliminated by an amino acid substitution at position 129 (phenylalanine 129), and four amino acids in the carboxyl-terminal half of the acidic cluster in ORF49 (i.e., aspartate-phenylalanine-aspartate-glutamate from positions 41 to 44 [41DFDE44]) were identified as its binding motif. Alanine substitutions in each domain rendered the ORF44F129A mutation lethal for VZV, similar to deletion of the entire ORF44. The phenotype of the ORF49-41AAAA44 mutation was comparable to that of the ORF49-defective virus, including small-plaque formation, impaired growth, and low infectious virus production. These results suggest that the interaction between ORF44 and ORF49 is essential for their role in VZV infection and that ORF49 is required for the efficient production of infectious progeny virus mediated by the conserved interaction between the two proteins.
Crystal Structure of the Nipah Virus Phosphoprotein Tetramerization Domain
Authors: Bruhn Jessica F. , Barnett Katherine C. , Bibby Jaclyn , Thomas Jens M. H. , Keegan Ronan M. , Rigden Daniel J. , Bornholdt Zachary A. , Saphire Erica Ollmann
Published: October 2013

The Nipah virus phosphoprotein (P) is multimeric and tethers the viral polymerase to the nucleocapsid. We present the crystal structure of the multimerization domain of Nipah virus P: a long, parallel, tetrameric, coiled coil with a small, α-helical cap structure. Across the paramyxoviruses, these domains share little sequence identity yet are similar in length and structural organization, suggesting a common requirement for scaffolding or spatial organization of the functions of P in the virus life cycle.
Cytomegalovirus Expresses the Chemokine Homologue vXCL1 Capable of Attracting XCR1
+
CD4
−
Dendritic Cells
Authors: Geyer Henriette , Hartung Evelyn , Mages Hans Werner , Weise Christoph , Belužić Robert , Vugrek Oliver , Jonjić Stipan , Kroczek Richard A. , Voigt Sebastian
Published: October 2013

Cytomegaloviruses (CMV) have developed various strategies to escape the immune system of the host. One strategy involves the expression of virus-encoded chemokines to modulate the host chemokine network. We have identified in the English isolate of rat CMV (murid herpesvirus 8 [MuHV8]) an open reading frame encoding a protein homologous to the chemokine XCL1, the only known C chemokine. Viral XCL1 (vXCL1), a glycosylated protein of 96 amino acids, can be detected 13 h postinfection in the supernatant of MuHV8-infected rat embryo fibroblasts. vXCL1 exclusively binds to CD4
−
rat dendritic cells (DC), a subset of DC that express the corresponding chemokine receptor XCR1. Like endogenous rat XCL1, vXCL1 selectively chemoattracts XCR1
+
CD4
−
DC. Since XCR1
+
DC in mice and humans have been shown to excel in antigen cross-presentation and thus in the induction of cytotoxic CD8
+
T lymphocytes, the virus has apparently hijacked this gene to subvert cytotoxic immune responses. The biology of vXCL1 offers an interesting opportunity to study the role of XCL1 and XCR1
+
DC in the cross-presentation of viral antigens.