bluuebunny/crossref_metadata_2025 huggingface dataset:
Speech-Sound Discrimination in School-Age Children
Authors: Kraus Nina , Koch Dawn Burton , McGee Therese J. , Nicol Trent G. , Cunningham Jenna
Published: July 2014

This study measured behavioral speech-sound discrimination and a neurophysiologic correlate of discrimination in normal school-age children (ages 6 to 15) to determine if developmental effects exist. Just noticeable differences (JNDs) and mismatch responses (MMNs) were assessed for synthetic syllables that differed in third-formant onset frequency (/da-ga/) and formant transition duration (/ba-wa/). These stimuli were selected because children with learning problems often find it difficult to discriminate rapid spectrotemporal changes like /da-ga/, whereas the ability to distinguish /ba-wa/ is relatively unimpaired. Results indicate that JNDs for /da-ga/ show no developmental effects and that JNDs for /ba-wa/ decrease slightly with age (although likely for task-related reasons). MMNs elicited by two /da-ga/ stimulus pairs (onset frequency differences=20 Hz, 280 Hz) and three /ba-wa/ stimulus pairs (transition duration differences=3, 5, 15 ms) showed no systematic or significant differences for onset latency, duration, or area as a function of age. Normative JND and MMN data are provided. These norms provide a metric against which children with suspected central auditory processing difficulties or auditory-based language disorders can be compared.
Early Childhood Stuttering I
Authors: Yairi Ehud , Ambrose Nicoline Grinager
Published: July 2014

The divergent developmental course of stuttering with its two major paths, persistency and spontaneous (unaided) recovery, has been a focus of scientific attention because of its critical theoretical, research, and clinical perspectives. Issues concerning factors underlying persistency and recovery and their implications for early intervention have stirred considerable controversy among scientists. In light of the intense interest, the scarcity of direct essential epidemiological data concerning the magnitude of the two paths and the timing of recovery is problematic. Most past studies have used retrospective methodologies. The few longitudinal studies have been severely limited in scope or objective data. The purpose of the investigation reported herein is to study the pathognomonic course of stuttering during its first several years in early childhood with special reference to the occurrence of persistent and spontaneously recovered forms of the disorder. Employing longitudinal methodology with thorough, frequent periodic follow-up observations, multiple testing, and recording of extensive speech samples, 147 preschool children who stutter have been closely followed for several years from near the onset of stuttering. In this, the first of three related articles, we present findings regarding the current stuttering status of 84 of these children, who have been followed for a minimum of 4 years after their onset of stuttering. The data indicate continuous diminution in the frequency and severity of stuttering over time as many children progressed toward recovery. Our findings lead to conservative estimates of 74% overall recovery and 26% persistency rates. The process of reaching complete recovery varied in length among the children and was distributed over a period of 4 years after onset. Detailed analyses of phonological and language skills pertaining to differentiation of the developmental paths of children who persist and those who recover are presented in the two other articles in the series (E. P. Paden et al., 1999, and R. V. Watkins et al., 1999).
Testing the Generalized Slowing Hypothesis in Specific Language Impairment
Authors: Windsor Jennifer , Hwang Mina
Published: July 2014

This study investigated the proposition that children with specific language impairment (SLI) show a generalized slowing of response time (RT) across tasks compared to chronological-age (CA) peers. Three different theoretical models consistent with the hypothesis of generalized slowing—a proportional, linear, and nonlinear model—were examined using regression analyses of group RT data. Each model was an excellent fit with the RT data. The most parsimonious model indicated that the SLI group was proportionally slower than the CA group. Mean RTs of the SLI group were about one fifth slower across tasks than the CA group's mean RTs. Less slowing was evident for a subgroup of young children with expressive SLI than for children with mixed (expressive and receptive) SLI. Although the mean RT data reflected many individual SLI children's RT performance, not all SLI children showed generalized slowing.
Observed and Reported Expressive Vocabulary and Word Combinations in Bilingual Toddlers
Authors: Patterson Janet L.
Published: July 2014

The consistency of parental reports of expressive vocabulary and word combinations with observed expressive language among 21- to 27-month-old children exposed to English and Spanish on a regular basis was the focus of this investigation. Parental reports were obtained using the Spanish-English Vocabulary Checklist (Patterson, 1998), an adaptation of the Language Development Survey (Rescorla, 1989). The number of different words parents reported was correlated (
r
=.66) with the number of different words the children used during a 30-min videotaped interaction with the reporting parent. Parental reports of whether the child was combining words and estimates of proportion of the child's use of Spanish and English also were consistent with the children's language use during the 30-min language samples.
The Effects of Inflectional Variation on Fast Mapping of Verbs in English and Spanish
Authors: Bedore Lisa M. , Leonard Laurence B.
Published: July 2014

To use morphological cues for syntactic bootstrapping, children must recognize that inflectionally varying words (e.g.,
pushes, pushed
) are instances of the same word. Children who are exposed to languages with richer inflectional morphologies than English, such as Spanish, encounter instances of inflectional variation more often. Thus they may learn to recognize inflectionally varying words as instances of the same word at an earlier age than do learners of English. English- and Spanish-learning 3-year olds were taught novel verbs in a fast mapping task under two conditions: no-inflectional variation in which inflections did not vary between exposure and testing (e.g.,
neps, neps
) and inflectional variation in which inflections alternated between exposure and testing (e.g.,
neps, nepped
). Children’s scores were significantly higher in the no-variation condition than in the variation condition. There were no significant differences between the performance of the language groups. These findings suggest that even children acquiring languages with relatively rich verbal inflection paradigms may not be able to consistently parse stems and inflections to associate inflectionally varying forms.
Production of Sentence-Final Intonation Contours by Hearing-Impaired Children
Authors: Allen George D. , Arndorfer Patricia M.
Published: July 2014

Studies of intonation in the hearing impaired (HI) are often concerned with either objective measures or listener perceptions. Less often has the focus been on how these two aspects of communication interrelate. This study examined the relationship between certain acoustic parameters and listeners’ perceptions of intonation contours produced by HI children. Six severe-to-profound HI children and 6 normal-hearing (NH) children, ages 7;9 to 14;7, were individually tape recorded while reading 10 declarative sentences and 10 phonemically matched interrogative sentences within the context of a script. Each sentence ended with a carefully chosen disyllabic (target) word. Twelve adult listeners, inexperienced with the speech of the HI, listened to a randomized audio tape presentation of all of these productions and categorized each one as a statement, question, or other. Fundamental frequency (FO) and duration measurements were obtained for the target (final) word of each sentence, and intensity measures were recorded for each entire sentence. Acoustic analysis showed that all 6 of the NH children and 4 of the 6 HI children produced acoustically different intonation contours for declarative versus interrogative sentences. The HI children’s productions were, in general, similar to the NH children, in that they used FO, duration, and intensity cues to mark the distinction. Their contrastive use of these acoustic cues, however, was less pronounced than for the NH children. Analysis of listener responses indicated that, although listeners were able to differentiate between some of the declarative and interrogative sentences produced by these 4 HI children, judgments corresponded with their intended type less often for the HI than for the NH children. (Judgments of NH children’s utterances were 100% correct.) Multiple logistic regression of listeners’ responses to the HI children’s utterances showed that 4 acoustic measures, all derived from the sentence-final word, were significantly predictive: (1) sentence-final FO, (2) slope between the target word’s initial and final FO, (3) duration of the target word, and (4) dB difference between the target word’s 1st and 2nd syllables. Results were similar for the NH children’s data, except that the ratio of the 2 syllables’ durations was significant, rather than total word duration. These findings differ in several important ways from previously published data for HI children’s intonation contours and suggest that many HI children have the ability to benefit substantially from training in the production of intonation.
Timing and Intensity Variability in the Metronomic Speech of Stuttering and Nonstuttering Speakers
Authors: Boutsen Frank R. , Brutten Gene J. , Watts Christopher R.
Published: July 2014

The timing and intensity variability of 8 adults who stutter and 8 age-matched fluent speakers was investigated under metronomic conditions. Participants were required to produce double or triple-stress patterns at a slow speech rate (1 syllable/870 ms) when repeating the syllable /stæt/ or /stræt/ nine times. Measures that are sensitive to cyclic rather than overall variation in syllable timing and intensity were employed. Specifically, durational variation between successive syllable onsets as well as intensity variation of the beginning consonant and vowel in successive syllables were computed. Results revealed that, although intensity variation was similar, the timing of successive syllables of persons who stutter was significantly more variable than that of persons who do not stutter. These outcomes are discussed in relation to previous experiments of timing control of persons who stutter and normally fluent persons during metronomic stimulation.
Acoustic Voice Analysis by Means of the Hoarseness Diagram
Authors: Fröhlich Matthias , Michaelis Dirk , Strube Hans Werner , Kruse Eberhard
Published: July 2014

The hoarseness diagram (Michaelis, Fröhlich, & Strube, 1998a) has been proposed as a new approach to describe different acoustic properties of voices. To test its performance in the analysis of pathologically disturbed and normal voices five requirements are suggested that should be met by any acoustic voice-analysis protocol to be used in voice research and clinical practice. The hoarseness diagram is then tested with regard to these requirements. Individual voices are found to show a satisfactory localization in the diagram. Aspects of stationarity are discussed in the context of four case studies. The different cases illustrate that changes in the acoustic analysis results are observed if the voice-generation conditions change, whereas results are stationary if phonation conditions do not change. Different pathological voice groups defined on grounds of the specific phonation mechanism are found to map to specific regions of the hoarseness diagram, with differences between group locations being significant. All results can be interpreted without exceptions if the two hoarseness diagram coordinates are taken to reflect the vibrational irregularity of the voice-generation mechanisms on the one side and the degree of closure of the vibrating structures on the other side. The hoarseness diagram and its underlying algorithms are thus shown to constitute a useful approach to acoustic voice analysis in research and clinical practice. The tests themselves demonstrate several application possibilities, including the quantitative monitoring of individual voices.
Tense and Temporality
Authors: Paradis Johanne , Crago Martha
Published: July 2014

This study compares the morphosyntax of children with SLI to the morphosyntax of children acquiring a second language (L2) to determine whether the optional infinitive phenomenon (M. Rice, K. Wexler, & P. Cleave, 1995; K. Wexler, 1994) is evident in both learner groups and to what extent cross-learner similarities exist. We analyzed spontaneous production data from French-speaking children with SLI, English-speaking L2 learners of French, and French-speaking controls, all approximately 7 years old. We examined the children's use of tense morphology, temporal adverbials, agreement morphology, and distributional contingencies associated with finiteness. Our findings indicate that the use of morphosyntax by children with SLI and by L2 children has significant similarities, although certain specific differences exist. Both the children with SLI and the L2 children demonstrate optional infinitive effects in their language use. These results have theoretical and clinical relevance. First, they suggest that the characterization of the optional infinitive phenomenon in normal development as a consequence of very early neurological change may be too restrictive. Our data appear to indicate that the mechanism underlying the optional infinitive phenomenon extends to normal (second) language learning after the primary acquisition years. Second, they indicate that tense-marking difficulty may not be an adequate clinical marker of SLI when comparing children with impairment to both monolingual and bilingual peers. A more specific clinical marker would be more effective in diagnosing disordered populations in a multilingual context.
Effects of Age and Hearing Sensitivity on the Use of Prosodic Information in Spoken Word Recognition
Authors: Wingfield Arthur , Lindfield Kimberly C. , Goodglass Harold
Published: July 2014

It is well known that spoken words can often be recognized from just their onsets and that older adults require a greater word onset duration for recognition than young adults. In this study, young and older adults heard either just word onsets, word onsets followed by white noise indicating the full duration of the target word, or word onsets followed by a low-pass-filtered signal that indicated the number of syllables and syllabic stress (word prosody) in the absence of segmental information. Older adults required longer stimulus durations for word recognition under all conditions, with age differences in hearing sensitivity contributing significantly to this age difference. Within this difference, however, word recognition was facilitated by knowledge of word prosody to the same degree for young and older adults. These findings suggest, first, that listeners can detect and utilize word stress in making perceptual judgments and, second, that this ability remains spared in normal aging.
Practice and List Effects on the Synthetic Sentence Identification Test in Young and Elderly Listeners
Authors: Feeney M. Patrick , Hallowell Brooke
Published: July 2014

A high prevalence of central auditory processing disorders (CAPD) has been reported in the elderly based on scores for the Synthetic Sentence Identification Test (SSI). This study examined practice effects and list differences on the Auditec version of the SSI with an ipsilateral competing message in 30 young and 20 elderly participants. Results for the younger participants suggested that a minimum of one practice list should be used with the SSI, whereas results for the elderly participants suggested that a minimum of three practice lists should be used. The binomial model of A. R. Thornton and M. J. M. Raffin (1978) was suggested for use in determining the required number of lists needed to obtain reliable SSI performance. Significant list differences were found with the Auditec version of the SSI. It was recommended to use only Lists A, C, D, E, G, and I for consistent results across lists. Practice effects and list differences should be accounted for when using the SSI for the assessment of CAPD in elderly and young listeners.
Variations in the Relative Speeds of Orofacial Structures With Stuttering Severity
Authors: McClean Michael D. , Runyan Charles M.
Published: July 2014

Stuttering can be characterized in part as a disorder in the coordination of different muscle systems. In light of basic aspects of orofacial physiology and development, the speeds of the lips and tongue relative to the jaw may be an important dimension for evaluating motor coordination among persons who stutter (PWS). To test this idea, an electromagnetic system was used to obtain measures of lip, tongue, and jaw speed in 38 adults (29 PWS and 9 normally fluent speakers, NFS) as they repeated a simple speech utterance at a normal rate. Using categorical ratings of stuttering severity, ratios of tongue speed to jaw speed were significantly greater in PWS rated as severe, compared to NFS and other PWS. Significant increases in lower lip-to-jaw and tongue-to-jaw speed ratios with stuttering severity were also reflected in correlation analyses relating speed ratios to a continuous measure of stuttering severity. These trends in speed ratio were related to increases in lower lip and tongue speed and decreases in jaw speed with stuttering severity. Sources of the speed differences are discussed in relation to underlying muscle activity, motor compensation processes in adults, and the development of orofacial motor control in children who stutter.
Self-Assessment of Pediatric Feeding Therapists in the State of Illinois
Authors: Fishbein Mark , Flock Sarah , Benton Kathryn
Published: July 2014

Introduction:

The care of infants and children with feeding and swallowing disorders requires specialized skills and strategies. Therapist certification is often available for hospital-based feeding, yet due to increasing demand, more non-certified, state-provided therapists are providing treatment. However, their skill set is uncertain and has yet to be explored. This investigation provides insight into therapist skill level and self-perceived proficiency.

Methods:

Feeding therapists throughout the state were surveyed for CEU, caseload, and work environment. Individual skill set and self-reliance with clinical vignettes were assessed a by Likert scale.

Results:

Early Intervention: (0 to 3 years of age) outnumbered outpatient, school, and hospital-based therapists. Limited training and caseload were prevalent and associated with poorer clinical skills. Both early intervention and hospital-based therapists reported proficiency in managing infants with dysphagia, however hospital-based therapists were most self-reliant.

Conclusion:

A certification process and associated clinical pathway is recommended for feeding therapists to provide standardized services throughout state.
SIG 16 Perspectives Vol. 13, No. 1, March 2012
Authors: Schraeder Trici
Published: July 2014

Sorry, this activity is no longer available for CEUs. Visit the SIG 16 page on the
ASHA Store
to see available CE activities.

Use the CE questions PDF here as study questions to guide your Perspectives reading.
SIG 16 Perspectives Vol. 14, No. 1, March 2013
Authors: Morgan Ruth
Published: July 2014

Sorry, this activity is no longer available for CEUs. Visit the SIG 16 page on the
ASHA Store
to see available CE activities.

Use the CE questions PDF here as study questions to guide your Perspectives reading.
A Survey of U.S. Immigrants: Service Delivery Issues for School-Based SLPs
Authors: Roseberry-McKibbin Celeste
Published: July 2014

In the 21st century, many residents of the United States are immigrants. Increasing numbers of immigrants and their children present a unique challenge for school-based speech-language pathologists (SLPs). In this study, 376 immigrants from 82 different countries were interviewed about a variety of issues, including their greatest challenges living in the United States, as well as their perceptions of SLPs and SLPs’ services. Practical implications are discussed.
SIG 3 Perspectives Vol. 23, No. 1, March 2013
Authors: Vinson Kimberly
Published: July 2014

Sorry, this activity is no longer available for CEUs. Visit the SIG 3 page on the
ASHA Store
to see available CE activities.

Use the CE questions PDF here as study questions to guide your Perspectives reading.
Telehealth and the Treatment of Voice Disorders: A Discussion Regarding Evidence
Authors: Kelchner Lisa
Published: July 2014

Telehealth is becoming a major component of healthcare delivery and consumption. Although it has a substantial history internationally and within certain U.S. health sectors (e.g., military, transport medicine, home health care), widespread application to broader populations of U.S. health care consumers has taken place within only the last decade. Telehealth permits increased access to care, particularly for rural and underserved populations (Mashima & Doarn, 2008). Additional benefits include improved convenience, reduced healthcare costs, and greater opportunity for supported self-management in the patient’s own environment. Moreover, given the use of technology to manage all other aspects of personal life, the health care consumer should expect that medicine and allied health will make progress toward adapting their traditional models of care to more effective and efficient methods.
On self-preservation and log-similarity in a slightly heated axisymmetric mixing layer
Authors: Thiesset F. , Schaeffer V. , Djenidi L. , Antonia R. A.
Published: July 2014

This paper reports an experimental investigation of self-preservation for one- and two-point statistics in a slightly heated axisymmetric mixing layer. Results indicate that the longitudinal velocity fluctuation u seems to approach self-preservation more rapidly than either the transverse velocity fluctuation v or the scalar fluctuation θ. The Reynolds number Reδ = U0δ/ν (U0 being the jet inlet velocity and δ the momentum thickness) that ought to be achieved for the one-point statistics to behave in a self-similar fashion is assessed. Second, the relevance of different sets of similarity variables for normalizing the energy spectra and structure functions is explored. In particular, a new set of shear similarity variables, emphasizing the range of scales influenced by the mean velocity and temperature gradient, is derived and tested. Since the Reynolds number based on the Taylor microscale increases with respect to the streamwise distance, complete self-preservation cannot be satisfied; instead, the range of scales over which spectra and structure functions comply with self-preservation depends on the particular choice of similarity variables. A similarity analysis of the two-point transport equation, which features the large scale production term, is performed and confirms this. Log-similarity, which implicitly accounts for the variation of the Reynolds number, is also proposed and appears to provide a reasonable approximation to self-preservation, at least for u and θ.
Note: Simple vacuum feedthrough for optical fiber with SubMiniature version A connectors at both ends
Authors: Kirilov K. M. , Denkova D. , Tsutsumanova G. G. , Russev S. C.
Published: July 2014

We present a simple way to insert an optical fiber, with existing standard SubMiniature version A connectors on both ends into a vacuum system. The fitting is tested in scanning electron microscope, at working pressures down to 2 × 10−5 mbar for cathodoluminescent measurements. With slight modifications this fitting could be successfully adapted for optical fiber insertion into pressurized systems.
Communication: A scaling approach to anomalous diffusion
Authors: Kneller Gerald R.
Published: July 2014

The paper presents a rigorous derivation of the velocity autocorrelation function for an anomalously diffusing slow solute particle in a bath of fast solvent molecules. The result is obtained within the framework of the generalized Langevin equation and uses only scaling arguments and identities which are based on asymptotic analysis. It agrees with the velocity autocorrelation function of an anomalously diffusing Rayleigh particle whose dynamics is described by a fractional Ornstein-Uhlenbeck process in velocity space. A simple semi-analytical example illustrates under which conditions the latter model is appropriate.
Lattice thermal conductivity of crystalline and amorphous silicon with and without isotopic effects from the ballistic to diffusive thermal transport regime
Authors: Park Minkyu , Lee In-Ho , Kim Yong-Sung
Published: July 2014

Thermal conductivity of a material is an important physical parameter in electronic and thermal devices, and as the device size shrinks down, its length-dependence becomes unable to be neglected. Even in micrometer scale devices, materials having a long mean free path of phonons, such as crystalline silicon (Si), exhibit a strong length dependence of the thermal conductivities that spans from the ballistic to diffusive thermal transport regime. In this work, through non-equilibrium molecular-dynamics (NEMD) simulations up to 17 μm in length, the lattice thermal conductivities are explicitly calculated for crystalline Si and up to 2 μm for amorphous Si. The Boltzmann transport equation (BTE) is solved within a frequency-dependent relaxation time approximation, and the calculated lattice thermal conductivities in the BTE are found to be in good agreement with the values obtained in the NEMD. The isotopic effects on the length-dependent lattice thermal conductivities are also investigated both in the crystalline and amorphous Si.
Comment on “Evaluation of the spatial distribution of series and shunt resistance of a solar cell using dark lock-in thermography” [J. Appl. Phys. 115, 034901 (2014)]
Authors: Breitenstein O. , Rißland S.
Published: July 2014

In a recent article, Chung et al. [J. Appl. Phys. 115, 034901 (2014)] proposed a novel method to measure series resistances in solar cells quantitatively by dark lock-in thermography. However, the theory to this method contains a mathematical fault; therefore, the method cannot work as expected. Some unphysical predictions and consequences of this theory are reported.
Light-induced hysteresis and recovery behaviors in photochemically activated solution-processed metal-oxide thin-film transistors
Authors: Jo Jeong-Wan , Kim Yong-Hoon , Park Sung Kyu
Published: July 2014

In this report, photo-induced hysteresis, threshold voltage (VT) shift, and recovery behaviors in photochemically activated solution-processed indium-gallium-zinc oxide (IGZO) thin-film transistors (TFTs) are investigated. It was observed that a white light illumination caused negative VT shift along with creation of clockwise hysteresis in electrical characteristics which can be attributed to photo-generated doubly ionized oxygen vacancies at the semiconductor/gate dielectric interface. More importantly, the photochemically activated IGZO TFTs showed much reduced overall VT shift compared to thermally annealed TFTs. Reduced number of donor-like interface states creation under light illumination and more facile neutralization of ionized oxygen vacancies by electron capture under positive gate potential are claimed to be the origin of the less VT shift in photochemically activated TFTs.
Micropatterned Arrays of ZnSe Nanospheres as Antireflection Coatings
Authors: Florence S. Sasi , Sachan Priyanka , Gupta Raju Kumar , John Rita , Mahalingam Umadevi
Published: July 2014

In this work, we demonstrate deposition of micro-arrays of ZnSe nanospheres on Si (100) substrate using simple thermal evaporation on a self-assembled sacrificial polystyrene (PS) mask. The results have been compared with the deposition on unpatterned gold catalyst- and SU-8 (negative photoresist)-coated Si substrates. The deposited ZnSe nanospheres properties were characterised by X-ray diffraction, atomic force microscopy (AFM), scanning electron microscopy (SEM), Raman, photoluminescence, and UV-vis spectroscopies. The X-ray diffraction patterns of the films exhibited reflection corresponding to the cubic (111) phase and showed polycrystallinity with a cubic (zinc blende) structure. The SEM and AFM images indicated that the particles were well dispersed and spherical in shape. The micro-arrays of ZnSe nanospheres on a self-assembled sacrificial PS mask showed excellent structural, morphological, and optical properties and demonstrated its usage in photovoltaic devices as an improved superior antireflective coating. The reflectance of the micro-arrays of ZnSe nanospheres on a self-assembled sacrificial PS mask decreased to nearly half of that of the ZnSe nanospheres fabricated on Au- and SU-8-coated Si substrates in the range of 300–800 nm. Due to the well aligned and patterned surfaces, these noble textured ZnSe nanospheres may be suitable for low cost, large area photovoltaic devices and other antireflection applications.
CRTC1/MAML2 gain-of-function interactions with MYC create a gene signature predictive of cancers with CREB–MYC involvement
Authors: Amelio Antonio L. , Fallahi Mohammad , Schaub Franz X. , Zhang Min , Lawani Mariam B. , Alperstein Adam S. , Southern Mark R. , Young Brandon M. , Wu Lizi , Zajac-Kaye Maria , Kaye Frederic J. , Cleveland John L. , Conkright Michael D.
Published: July 2014

Significance

The prevailing dogma since the identification of the
t
(11, 19) translocation gene product as a fusion of the cAMP response element binding protein (CREB)-regulated transcriptional coactivator 1 (CRTC1) and the NOTCH coactivator mastermind-like 2 (MAML2) in malignant salivary gland tumors has been that aberrant activation of CREB and/or NOTCH transcription programs drives oncogenesis. However, combined expression of the parental coactivator molecules CRTC1 and MAML2 is not sufficient to induce transformation, suggesting an added level of complexity. Here we describe gain-of-function interactions between the CRTC1/MAML2 (C1/M2) coactivator fusion and myelocytomatosis oncogene (MYC) oncoproteins that are necessary for C1/M2-driven transformation. Our findings suggest that targeting the C1/M2–MYC interface represents an attractive strategy for the development of effective and safe anticancer therapeutics in tumors harboring the
t
(11, 19) translocation.
Spatiotemporal control of epithelial remodeling by regulated myosin phosphorylation
Authors: Kasza Karen E. , Farrell Dene L. , Zallen Jennifer A.
Published: July 2014

Spatiotemporally regulated actomyosin contractility generates the forces that drive epithelial cell rearrangements and tissue remodeling. Phosphorylation of the myosin II regulatory light chain (RLC) promotes the assembly of myosin monomers into active contractile filaments and is an essential mechanism regulating the level of myosin activity. However, the effects of phosphorylation on myosin localization, dynamics, and function during epithelial remodeling are not well understood. In
Drosophila
, planar polarized myosin contractility is required for oriented cell rearrangements during elongation of the body axis. We show that regulated myosin phosphorylation influences spatial and temporal properties of contractile behavior at molecular, cellular, and tissue length scales. Expression of myosin RLC variants that prevent or mimic phosphorylation both disrupt axis elongation, but have distinct effects at the molecular and cellular levels. Unphosphorylatable RLC produces fewer, slower cell rearrangements, whereas phosphomimetic RLC accelerates rearrangement and promotes higher-order cell interactions. Quantitative live imaging and biophysical approaches reveal that both phosphovariants reduce myosin planar polarity and mechanical anisotropy, altering the orientation of cell rearrangements during axis elongation. Moreover, the localized myosin activator Rho-kinase is required for spatially regulated myosin activity, even when the requirement for phosphorylation is bypassed by the expression of phosphomimetic myosin RLC. These results indicate that myosin phosphorylation influences both the level and the spatiotemporal regulation of myosin activity, linking molecular properties of myosin activity to tissue morphogenesis.
The early rise and late demise of New Zealand’s last glacial maximum
Authors: Rother Henrik , Fink David , Shulmeister James , Mifsud Charles , Evans Michael , Pugh Jeremy
Published: July 2014

Significance

We present here a comprehensive record of glaciation from a New Zealand valley glacier system covering the critical 15,000-y period from the local last glacial maximum (LGM) to near the end of the last ice age. This record from a key site in the midlatitude Southern Hemisphere shows that the largest glacial advance did not coincide with the coldest temperatures during this phase. We also show that the regional post-LGM ice retreat was very gradual, contrary to the rapid ice collapse widely inferred. This demonstrates that glacial records from New Zealand are neither synchronous with nor simply lag or lead Northern Hemisphere ice sheet records, which has important implications for the reconstruction of past interhemispheric climate linkages and mechanisms.
Global view of the protein universe
Authors: Nepomnyachiy Sergey , Ben-Tal Nir , Kolodny Rachel
Published: July 2014

Significance

To globally explore protein space, we use networks to present similarities among a representative set of all known domains. In the “domain network” edges connect domains that share “motifs,” i.e., significantly sized segments of similar sequence and structure, and in the “motif network” edges connect recurring motifs that appear in the same domain. The networks offer a way to organize protein space, and examine how the organization changes upon changing the definition of “evolutionary relatedness” among domains. For example, we use them to highlight and characterize the uniqueness of a class of domains called alpha/beta, in which the alpha and beta elements alternate. The networks can also suggest evolutionary paths between domains, and be used for protein search and design.
Footprint of
Deepwater Horizon
blowout impact to deep-water coral communities
Authors: Fisher Charles R. , Hsing Pen-Yuan , Kaiser Carl L. , Yoerger Dana R. , Roberts Harry H. , Shedd William W. , Cordes Erik E. , Shank Timothy M. , Berlet Samantha P. , Saunders Miles G. , Larcom Elizabeth A. , Brooks James M.
Published: July 2014

Significance

The
Deepwater Horizon
blowout released more oil and gas into the deep sea than any previous spill. Soon after the well was capped, a deep-sea community 13 km southwest of the wellhead was discovered with corals that had been damaged by the spill. Here we show this was not an isolated incident; at least two other coral communities were also impacted by the spill. One was almost twice as far from the wellhead and in 50% deeper water, considerably expanding the known area of impact. In addition, two of four other newly discovered coral communities in the region were fouled with commercial fishing line, indicating a large cumulative effect of anthropogenic activities on the corals of the deep Gulf of Mexico.
Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2′-deoxycytidine
Authors: Li Deyu , Fedeles Bogdan I. , Singh Vipender , Peng Chunte Sam , Silvestre Katherine J. , Simi Allison K. , Simpson Jeffrey H. , Tokmakoff Andrei , Essigmann John M.
Published: July 2014

Significance

Unlike conventional antiviral therapy, lethal mutagenesis is a therapeutic strategy that exploits the high mutation rates of certain viruses. It works by intentionally increasing the viral mutation rate, causing excessive error accumulation and viral population collapse. The mutagenic nucleoside analog 5-aza-5,6-dihydro-2′-deoxycytidine (KP1212) is specifically designed to use lethal mutagenesis against HIV. The mechanism of KP1212 mutagenesis was proposed to involve tautomerism—the repositioning of active protons on the nucleic acid base on a fast time scale. Using a multifaceted approach, we demonstrate that KP1212 exists in multiple tautomeric forms, and that the tautomeric distribution correlates with the mutagenic properties of KP1212. This work also provides a toolset for studying tautomerism in nucleic acids and developing the next-generation antiviral lethal mutagens.
Upper-tropospheric moistening in response to anthropogenic warming
Authors: Chung Eui-Seok , Soden Brian , Sohn B. J. , Shi Lei
Published: July 2014

Significance

The fact that water vapor is the most dominant greenhouse gas underscores the need for an accurate understanding of the changes in its distribution over space and time. Although satellite observations have revealed a moistening trend in the upper troposphere, it has been unclear whether the observed moistening is a facet of natural variability or a direct result of human activities. Here, we use a set of coordinated model experiments to confirm that the satellite-observed increase in upper-tropospheric water vapor over the last three decades is primarily attributable to human activities. This attribution has significant implications for climate sciences because it corroborates the presence of the largest positive feedback in the climate system.
Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs
Authors: Matkovich Scot J. , Edwards John R. , Grossenheider Tiffani C. , de Guzman Strong Cristina , Dorn Gerald W.
Published: July 2014

Significance

The role of noncoding RNAs in mammalian biology is of great interest, especially since the Encyclopedia of DNA Elements results were published. We and others have studied microRNAs in the heart, but little is known about their larger cousins, long noncoding RNAs (lncRNAs). Here, we used genome-wide sequencing and improved bioinformatics to quantify lncRNA expression in mouse hearts, define a subset of cardiac-specific lncRNAs, and measure dynamic lncRNA regulation during the transition between embryo and adult, and in the adult heart after experimental pressure overload (a model resembling human hypertensive cardiomyopathy). We linked specific regulated lncRNAs to cardiac-expressed mRNAs that they target and, through network analyses, discovered a broader role of regulated cardiac lncRNAs as modulators of key cardiac transcriptional pathways.
Photoreceptor partner FHY1 has an independent role in gene modulation and plant development under far-red light
Authors: Chen Fang , Li Bosheng , Demone Jordan , Charron Jean-Benoit , Shi Xiarong , Deng Xing Wang
Published: July 2014

Significance

Phytochrome A (phyA) is the photoreceptor in
Arabidopsis
that mediates the far-red light high radiance response. Its partner FHY1 (FAR-RED ELONGATED HYPOCOTYL 1) is involved in each step of phyA signaling, including phyA nuclear translocation, interaction with transcription factors, and association with gene promoters. Although there is evidence that an FHY1-independent nuclear phyA signaling branch is present, whether phyA and FHY1 in fact act separately is currently under debate. This study identifies phyA and FHY1 unique direct target genes and in particular analyzes the phyA-independent FHY1 nuclear actions involved in regulating gene transcription. Significant light has been shed on the molecular mechanisms through which phyA or FHY1 performs their own functions in response to the far-red light signal.
Quality control of assembly-defective U1 snRNAs by decapping and 5′-to-3′ exonucleolytic digestion
Authors: Shukla Siddharth , Parker Roy
Published: July 2014

Significance

Cellular RNAs undergo assembly with various proteins, which leads to the formation of functional ribonucleoprotein (RNP) complexes. Kinetic defects in the RNP assembly pathway, which affect the rate of RNP formation, can lead to a reduction in the levels of functional RNPs in the cell, and can lead to a disease state, which we classify as an “RNP assembly disease.” One example of this class of diseases is spinal muscular atrophy (SMA), where mutations in the assembly factor survival motor neuron lead to reduced small nuclear (sn)RNA and snRNP levels. Here we describe the decay pathways that regulate snRNA levels and function in the cell, prevention of which could be pertinent as a therapy for SMA.
Expression of recombinant alpha and beta tubulins from the yew Taxus cuspidata and analysis of the microtubule assembly in the presence of taxol
Authors: Kudo Yuma , Abe Akihiro , Ito Kumiko , Cho Yuko , Yotsu-Yamashita Mari , Konoki Keiichi
Published: July 2014

Taxol was originally isolated from the yew Taxus brevifolia. Because taxol inhibits the depolymerization of microtubules, the presence of a self-resistance mechanism in Taxus spp. was hypothesized. The cloning of the cDNA for alpha and beta tubulins from Taxus cuspidata and those from the human embryonic kidney cell line HEK293T revealed that the 26Asp, 359Arg, and 361Leu residues in the human beta tubulin, which are important for taxol binding, were replaced with Glu, Trp, and Met in the beta tubulin of T. cuspidata, respectively. The microtubule assembly of the recombinant alpha and beta tubulins was monitored turbidimetrically, and the results clearly demonstrated that the microtubule from T. cuspidata is less sensitive to taxol than that from HEK293T cells. The Taxus microtubule composed of the wild-type alpha tubulin and the beta tubulin with the E26D mutation restored the sensitivity to taxol. We thus postulated that the mutation identified in the beta tubulin of T. cuspidata plays a role in the self-resistance of this species against taxol.
Secularisation, anticlericalism and cremation within Italian cemeteries of the nineteenth century
Authors: Malone Hannah
Published: July 2014

This article examines the monumental cemeteries of nineteenth-century Italy with regard to their role as platforms for the tensions between Church and state. In that burial grounds were publically owned yet administered by the clergy, they represented a space where conflicts between secular and clerical powers might be played out – conflicts that reached a peak in the final decades of the Ottocento following the annexation of the Papal State to unified Italy. Particular attention is given to the adoption of cremation as a practice that was advocated by anticlerical, liberal and radical factions in opposition to the Catholic Church. That opposition was manifested in the design and layout of Italian burial grounds and in construction of new crematoria.
Effects of Tetrahydrobiopterin Oral Treatment in Hypoxia‐Induced Pulmonary Hypertension in Rat
Authors: Francis Bahaa N. , Hale Ashley , Channon Keith M. , Wilkins Martin R. , Zhao Lan
Published: July 2014

Endothelial nitric oxide synthase (eNOS) plays a major role in maintaining pulmonary vascular homeostasis. Tetrahydrobiopterin (BH4), an essential cofactor that stabilizes the dimerization of eNOS and balances nitric oxide (NO) and superoxide production, may have therapeutic potential in pulmonary hypertension. In the isolated perfused lung, we demonstrated a direct effect of exogenous administration of BH4 on pulmonary NO production, leading to acute vasorelaxation during the plateau phase of hypoxia‐induced pulmonary vasoconstriction. In the chronic hypoxia‐induced pulmonary hypertension rat model, chronic BH4 oral administration attenuated the pressor response to hypoxia (mean pulmonary artery pressure ± standard error of the mean, 31.8 ± 0.5 mmHg at 100 mg/kg/day; placebo group, 36.3 ± 0.6 mmHg; P < 0.05). During telemetric monitoring, right ventricular systolic pressure was reduced by approximately 50% after 1 week of BH4 treatment at 100 mg/kg/day. BH4 at 100 mg/kg/day reduced right ventricular hypertrophy (from 0.55 ± 0.01 to 0.50 ± 0.01; P < 0.05) and pulmonary vascular muscularization (from 79.2% ± 2% to 65.2% ± 3%; P < 0.01). BH4 treatment enhanced lung eNOS activity and reduced superoxide production, with a net increase in cyclic guanosine monophosphate levels. BH4 is effective in attenuating pulmonary hypertension in the hypoxic rat model when given as a rescue therapy.
𝐿^{𝑝} bounds for the commutators of singular integrals and maximal singular integrals with rough kernels
Authors: Chen Yanping , Ding Yong
Published: July 2014

The commutator of convolution type Calderon-Zygmund singular integral operators with rough kernels

p
.
v
.

Ω
(
x
)

|

x

|

n

p.v. \frac {\Omega (x)}{|x|^n}

are studied. The authors established the

L
p

(
1
>
p
>
∞
)

L^p\,(1>p>\infty )

boundedness of the commutators of singular integrals and maximal singular integrals with the kernel condition which is different from the condition

Ω
∈

H
1

(

S

n
−
1

)
.

\Omega \in H^1(S^{n-1}).
Hormones: A Very Short Introduction
Authors: Luck Martin
Published: July 2014

Hormones balance and coordinate the workings of the body. There are many misconceptions about the endocrine system and few people are aware of its nature and importance. Hormones: A Very Short Introduction explains what hormones are, where they come from, what they do, how they work, and how they evolved. It describes how the endocrine system operates, explaining how hormones regulate water, salt, and calcium in the body, how they affect reproduction and our appetites, and how they help us adjust to different environments, such as travel across time zones. The ethical and moral issues surrounding research methods, testing on animals, and hormone misuse are also considered.
Cyclosporine-inhibitable Cerebral Drug Transport Does Not Influence Clinical Methadone Pharmacodynamics
Authors: Meissner Konrad , Blood Jane , Francis Amber M. , Yermolenka Viktar , Kharasch Evan D.
Published: July 2014

Background:

Interindividual variability and drug interaction studies suggest that blood–brain barrier drug transporters mediate human methadone brain biodistribution. In vitro and animal studies suggest that methadone is a substrate for the efflux transporter P-glycoprotein, and that P-glycoprotein–mediated transport influences brain access and pharmacologic effect. This investigation tested whether methadone is a transporter in humans sample contents.

Methods:

Healthy volunteers received oral (N = 16) or IV (N = 12) methadone in different crossover protocols after nothing (control) or the validated P-glycoprotein inhibitor cyclosporine (4.5 mg/kg orally twice daily for 4 days, or 5 mg/kg IV over 2 h). Plasma and urine methadone and metabolite concentrations were measured by mass spectrometry. Methadone effects were measured by miosis and thermal analgesia (maximally tolerated temperature and verbal analog scale rating of discreet temperatures).

Results:

Cyclosporine marginally but significantly decreased methadone plasma concentrations and apparent oral clearance, but had no effect on methadone renal clearance or on hepatic N-demethylation. Cyclosporine had no effect on miosis or on R-methadone concentration–miosis relationships after either oral or IV methadone. Peak miosis was similar in controls and cyclosporine-treated subjects after oral methadone (1.4 ± 0.4 and 1.3 ± 0.5 mm/mg, respectively) and IV methadone (3.1 ± 1.0 and 3.2 ± 0.8 mm, respectively). Methadone increased maximally tolerated temperature, but analgesia testing was confounded by cyclosporine-related pain.

Conclusions:

Cyclosporine did not affect methadone pharmacodynamics. This result does not support a role for cyclosporine-inhibitable transporters mediating methadone brain access and biodistribution.