bluuebunny/crossref_metadata_2025_split huggingface dataset:
Path Analysis
Authors: Duffy Joseph R. , Watt James , Duffy Robert J. 
Published: July 2014

This tutorial paper explains, illustrates, and discusses path analysis, a powerful strategy for examining the plausibility and degree of causal relationships which are postulated to exist among a set of variables. In addition to its strength as a method of theory testing, path analysis is highly compatible with the kind of retrospective research which is so often used to study speech and language pathologies. One of its major advantages is that it allows explicit recognition of multiple, interacting causes of communication disorders and allows the researcher to evaluate the logical consequences of assumptions made about the specific nature of those causal relationships.
A summary of the meaning of causal relationships is followed by a presentation of the principles underlying path analysis, as well as an outline of its basic procedures. Also presented is an illustrative example of the application of path analysis to the evaluation of some competing causal theories of a communication disorder. Finally, the general advantages of path analysis and its applicability to the investigation of causal relationships in speech and language pathologies are summarized and discussed.
Auditory Distortion Products Measured With Averaged Auditory Evoked Potentials
Authors: Chertoff Mark E. , Hecox Kurt E. , Goldstein Robert 
Published: July 2014

The purpose of this investigation was to describe the properties of averaged auditory evoked potential distortion products (AEP-DPs) in guinea pigs. This study provided a step toward developing a clinical index of nonlinear processing of auditory signals and supplied a baseline for studies evaluating the effect of cochlear damage on AEP-DPs.
The amplitude of the AEP-DPs was evaluated as a function of f2/fl ratio (1.12–1.52) and primary frequency (500 Hz–2000 Hz). The amplitude of the AEP cubic difference tone (AEP-CDT) increased with increasing f2/fl ratio for the 500-Hz f1 primary and remained constant for the 800-Hz and 1700-Hz f1 primaries. The AEP-CDT generated by the 1100-Hz and 1400 Hz f1 primaries was maximum for the middle f2/fl ratios (1.22, 1.32, and 1.42). The AEP-CDT could not be distinguished from the noise floor for the 2000-Hz f1 primary. The AEP difference tone (AEP-DT) was larger and more frequently identified than the AEP-CDT. The amplitude of the AEP-DT decreased with an increase in f2/f1 ratio. The decrease was more pronounced for low-frequency f1 primaries than for high-frequency f1 primaries.
Effects of Signal and Masker Uncertainty on Children’s Detection
Authors: Allen Prudence , Wightman Frederic 
Published: July 2014

This paper reports the results of two experiments that examined the effects of signal and masker uncertainty on preschool-age children’s and adults’ detection of tonal signals in noise maskers. In Experiment 1 (signal uncertainty) the signal was randomly at 501 or 2818 Hz. The majority of the adult listeners showed a slight decrement in performance consistent with an ability to monitor both frequencies simultaneously. The majority of the children, however, showed no decrement in performance, suggesting that the children may not have focused attention at the signal frequency even when it was fixed. In Experiment 2 (masker uncertainty), random-frequency, random-level, tonal distracters were added to each interval of the 2 alternative-forced-choice (2afc) procedure. The effect of masker uncertainty was much larger than that of signal uncertainty. For most of the adult listeners and some of the children, the distracters produced higher thresholds (on average by 10 dB) and shallower psychometric function slopes. For most of the children, thresholds increased by 20 dB or more and psychometric functions were often nearly flat.
This paper reports the results of two experiments that examined the effects of signal and masker uncertainty on preschool-age children's and adults' detection of tonal signals in noise maskers. In Experiment 1 (signal uncertainty) the signal was randomly at 501 or 2818 Hz. The majority of the adult listeners showed a slight decrement in performance consistent with an ability to monitor both frequencies simultaneously. The majority of the children, however, showed no decrement in performance, suggesting that the children may not have focused attention at the signal frequency even when it was fixed. In Experiment 2 (masker uncertainty), random-frequency, random-level, tonal distracters were added to each interval of the 2 alternative-forced-choice (2afc) procedure. The effect of masker uncertainty was much larger than that of signal uncertainty. For most of the adult listeners and some of the children, the distracters produced higher thresholds (on average by 10 dB) and shallower psychometric function slopes. For most of the children, thresholds increased by 20 dB or more and psychometric functions were often nearly flat.
Speech Production in People Who Stutter: Testing the Motor Plan Assembly Hypothesis
Authors: Lieshout Pascal H.H.M. van , Hulstijn Wouter , Peters Herman F.M. 
Published: July 2014

The main purpose of the present study was to test the hypothesis that persons who stutter, when compared to persons who do not stutter, are less able to assemble abstract motor plans for short verbal responses. Subjects were adult males who stutter and age- and sex-matched control speakers, who were tested on naming pictures and words, using a choice-reaction time paradigm for both tasks. Words varied in the number of syllables (1, 2, and 3 syllables) and, for the bisyllabic words, also in the number of consonants (one or more) at the onset of the second syllable. Measurements consisted of speech reaction times, word durations, and measures of relative timing of specific motor events in the respiratory, phonatory, and articulatory subsystems.
Results indicated that, in spite of longer speech reaction times for persons who stutter in comparison to control speakers, there was no interaction with word size, a finding that does not lend support to the abovementioned hypothesis. Word durations were found to be longer for persons who stutter, and, in addition, there was an interaction of group with word size. Both findings were associated with longer delays for persons who stutter in the onset of upper lip integrated electromyographic (IEMG) activity and thoracic compression, and a group effect on the order of upper lip and lower lip IEMG onset. Findings are taken to suggest the possibility that persons who stutter may use different motor control strategies to compensate for a reduced verbal motor skill, and although the nature of this reduced skill is unknown, it is speculated that it relates to the processes involved in the integration of sensory-motor information.
Reflex Responses of Lip Muscles in Young and Older Women
Authors: Wohlert Amy B. 
Published: July 2014

The perioral reflex in response to innocuous mechanical stimulation of the lip vermilion was studied in 20 young and 20 older women. Responses to stimuli at the right and left sides of both the upper and lower lips were recorded. Results show significant specificity of response, especially for upper lip sites. Reflex response at the site of stimulation was greatest in amplitude and shortest in latency, followed by response at sites ipsilateral to the site of stimulation. Younger subjects showed greater localizing tendency than older subjects.
Stimulation was significantly less likely to produce a reflex response in the older group. When reflex responses did occur, they were significantly lower in amplitude and longer in latency than the responses of the younger group. Nonetheless, reflex responses were common in both groups, with responses at the site of stimulation occurring 78% of the time in older women and 90% of the time in younger women. Every participant showed at least one reflex response to lip stimulation. Results suggest decreasing complexity of synaptic drive to the perioral system in old age but also show that reflexive response does not deteriorate completely, remaining an available element for motor control in normal older women.
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.
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

SignificanceTo 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.
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.
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

Abstract
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.
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.
Hormones: A Very Short Introduction
Authors: Luck Martin 
Published: July 2014

Abstract
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

Abstract

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.
MIPSTR: a method for multiplex genotyping of germ-line and somatic STR variation across many individuals
Authors: Carlson Keisha D. , Sudmant Peter H. , Press Maximilian O. , Eichler Evan E. , Shendure Jay , Queitsch Christine 
Published: July 2014

AbstractShort tandem repeats (STRs) are highly mutable genetic elements that often reside in functional genomic regions. The cumulative evidence of genetic studies on individual STRs suggests that STR variation profoundly affects phenotype and contributes to trait heritability. Despite recent advances in sequencing technology, STR variation has remained largely inaccessible across many individuals compared to single nucleotide variation or copy number variation. STR genotyping with short-read sequence data is confounded by (1) the difficulty of uniquely mapping short, low-complexity reads and (2) the high rate of STR amplification stutter. Here, we present MIPSTR, a robust, scalable, and affordable method that addresses these challenges. MIPSTR uses targeted capture of STR loci by single-molecule Molecular Inversion Probes (smMIPs) and a unique mapping strategy. Targeted capture and mapping strategy resolve the first challenge; the use of single molecule information resolves the second challenge. Unlike previous methods, MIPSTR is capable of distinguishing technical error due to amplification stutter from somatic STR mutations. In proof-of-principle experiments, we use MIPSTR to determine germ-line STR genotypes for 102 STR loci with high accuracy across diverse populations of the plantA. thaliana.We show that putatively functional STRs may be identified by deviation from predicted STR variation and by association with quantitative phenotypes. Employing DNA mixing experiments and a mutant deficient in DNA repair, we demonstrate that MIPSTR can detect low-frequency somatic STR variants. MIPSTR is applicable to any organism with a high-quality reference genome and is scalable to genotyping many thousands of STR loci in thousands of individuals.