Effects of consonantal constrictions on voice quality.

A speech production experiment with electroglottography investigated how voicing is affected by consonants of differing degrees of constriction. Measures of glottal contact [closed quotient (CQ)] and strength of voicing [strength of excitation (SoE)] were used in conditional inference tree analyses. Broadly, the results show that as the degree of constriction increases, both CQ and SoE values decrease, indicating breathier and weaker voicing. Similar changes in voicing quality are observed throughout the course of the production of a given segment. Implications of these results for a greater understanding of source-tract interactions and for the phonological notion of sonority are discussed.

Acoustic voice variation within and between speakers.

Little is known about the nature or extent of everyday variability in voice quality. This paper describes a series of principal component analyses to explore within- and between-talker acoustic variation and the extent to which they conform to expectations derived from current models of voice perception. Based on studies of faces and cognitive models of speaker recognition, the authors hypothesized that a few measures would be important across speakers, but that much of within-speaker variability would be idiosyncratic. Analyses used multiple sentence productions from 50 female and 50 male speakers of English, recorded over three days. Twenty-six acoustic variables from a psychoacoustic model of voice quality were measured every 5 ms on vowels and approximants. Across speakers the balance between higher harmonic amplitudes and inharmonic energy in the voice accounted for the most variance (females = 20%, males = 22%). Formant frequencies and their variability accounted for an additional 12% of variance across speakers. Remaining variance appeared largely idiosyncratic, suggesting that the speaker-specific voice space is different for different people. Results further showed that voice spaces for individuals and for the population of talkers have very similar acoustic structures. Implications for prototype models of voice perception and recognition are discussed.

Towards understanding speaker discrimination abilities in humans and machines for text-independent short utterances of different speech styles.

Little is known about human and machine speaker discrimination ability when utterances are very short and the speaking style is variable. This study compares text-independent speaker discrimination ability of humans and machines based on utterances shorter than 2 s in two different speaking styles (read sentences and speech directed towards pets, characterized by exaggerated prosody). Recordings of 50 female speakers drawn from the UCLA Speaker Variability Database were used as stimuli. Performance of 65 human listeners was compared to i-vector-based automatic speaker verification systems using mel-frequency cepstral coefficients, voice quality features, which were inspired by a psychoacoustic model of voice perception, or their combination by score-level fusion. Humans always outperformed machines, except in the case of style-mismatched pairs from perceptually-marked speakers. Speaker representations by humans and machines were compared using multi-dimensional scaling (MDS). Canonical correlation analysis showed a weak correlation between machine and human MDS spaces. Multiple regression showed that means of voice quality features could represent the most important human MDS dimension well, but not the dimensions from machines. These results suggest that speaker representations by humans and machines are different, and machine performance might be improved by better understanding how different acoustic features relate to perceived speaker identity.

Effect of vitamin D on T-helper type 9 polarized human memory cells in chronic persistent asthma.

BACKGROUND: Vitamin D suppresses inflammation and vitamin D deficiency is linked to the severity of asthma symptoms. T-helper type 9 (TH9) cells are important in the pathogenesis, yet the effects of vitamin D on this subset of inflammatory T-helper cells from patients with chronic asthma is unknown. OBJECTIVE: To determine the effects of vitamin D and dexamethasone on TH9 memory cells from adults with chronic persistent asthma and on a recall response to dust mite allergen. METHODS: T-helper memory cells were cultured with cytokines that drive TH9 polarization with vitamin D and/or dexamethasone. Peripheral blood mononuclear cells (PBMCs) from patients with radioallergosorbent test results for house dust mite were stimulated with allergen in the presence or absence of vitamin D. Intracellular cytokines, transcription factors, and identification of cell surface phenotypic markers were determined by flow cytometry. RESULTS: Vitamin D decreased interleukin (IL)-9, IL-5, and IL-8 but increased IL-13(+) cells in TH9 cultures. Transcription factors PU.1 and interferon regulatory factor 4 were downregulated by vitamin D but not GATA3 and c-MAF. When PBMCs from patients with positive radioallergosorbent test results were stimulated with dust mite allergen, vitamin D decreased IL-9, IL-5, and IL-13 in T-helper cells (CD4(+)). TH9 cells present in a recall response were classically TH2 (CD294(+)), and polarization by transforming growth factor-ß and IL-4 altered that phenotype. CONCLUSION: Vitamin D decreased inflammatory cytokine profiles in TH9 memory cells and CD4(+) cells stimulated with dust mite allergen. Vitamin D is additive with dexamethasone in decreasing inflammatory cytokine production from T-cell subsets implicated in asthma.

Vocal fold vibratory patterns in tense versus lax phonation contrasts.

This study explores the vocal fold contact patterns of one type of phonation contrast--the tense vs lax phonation contrasts of three Yi (Loloish) languages. These contrasts are interesting because neither phonation category is very different from modal voice, and because both phonations are largely independent of the languages' tonal contrasts. Electroglottographic (EGG) recordings were made in the field, and traditional EGG measures were derived. These showed many small but significant differences between the phonations, with tense phonation having greater contact quotients and briefer but slower changes in contact. Functional data analysis was then applied to entire EGG pulse shapes. The resulting first principal component was found to be mostly strongly related to the phonation contrasts, and correlated with almost all the traditional EGG measures. Unlike the traditional measures, however, this component also seems to capture differences in abruptness of contact. Furthermore, previously collected perceptual responses from native speakers of one of the languages correlated better with this component than with any other EGG measure or any acoustic measure. The differences between these tense and lax phonations are not large, but apparently they are consistent enough, and perceptually robust enough, to support this linguistic contrast.

Voice quality and tone identification in White Hmong.

This study investigates the importance of source spectrum slopes in the perception of phonation by White Hmong listeners. In White Hmong, nonmodal phonation (breathy or creaky voice) accompanies certain lexical tones, but its importance in tonal contrasts is unclear. In this study, native listeners participated in two perceptual tasks, in which they were asked to identify the word they heard. In the first task, participants heard natural stimuli with manipulated F0 and duration (phonation unchanged). Results indicate that phonation is important in identifying the breathy tone, but not the creaky tone. Thus, breathiness can be viewed as contrastive in White Hmong. Next, to understand which parts of the source spectrum listeners use to perceive contrastive breathy phonation, source spectrum slopes were manipulated in the second task to create stimuli ranging from modal to breathy sounding, with F0 held constant. Results indicate that changes in H1-H2 (difference in amplitude between the first and second harmonics) and H2-H4 (difference in amplitude between the second and fourth harmonics) are independently important for distinguishing breathy from modal phonation, consistent with the view that the percept of breathiness is influenced by a steep drop in harmonic energy in the lower frequencies.

Visible-Light-Active BiOI/TiO2 Heterojunction Photocatalysts for Remediation of Crude Oil-Contaminated Water.

In this study, BiOI-sensitized TiO2 (BiOI/TiO2) nanocomposites with different levels of BiOI deposited via sequential ionic layer adsorption and reaction (SILAR) have been explored for the degradation of methyl orange, 4-chlorophenol (4-CP), and crude oil in water under visible (>400 nm) irradiation with excellent degradation performance. The reaction progress for methyl orange and 4-chlorophenol was monitored by a UV-vis spectrophotometer, and the degradation of the crude oil hydrocarbons was determined by GC-MS. The BiOI/TiO2 heterojunction improves separation of photogenerated charges, which enhances the degradation efficiency. Evaluation of the visible-light photocatalytic performance of the synthesized catalysts against methyl orange degradation confirmed that four SILAR cycles are the optimal deposition condition for the best degradation efficiency. The efficiency was further confirmed by degrading 4-CP and crude oil, achieving 38.30 and 85.62% degradation, respectively, compared with 0.0% (4-CP) and 70.56% (crude oil) achieved by TiO2. The efficiency of TiO2 in degrading crude oil was mainly due to adsorption along with photolysis. This study provides a simple and cost-effective alternative to traditional remediation methods requiring high energy consumption for remediation of crude oil-polluted water and refinery wastewater using visible-light photocatalysis along with adsorption.

Comparison of speaking fundamental frequency in English and Mandarin.

To determine if the speaking fundamental frequency (F0) profiles of English and Mandarin differ, a variety of voice samples from male and female speakers were compared. The two languages' F0 profiles were sometimes found to differ, but these differences depended on the particular speech samples being compared. Most notably, the physiological F0 ranges of the speakers, determined from tone sweeps, hardly differed between the two languages, indicating that the English and Mandarin speakers' voices are comparable. Their use of F0 in single-word utterances was, however, quite different, with the Mandarin speakers having higher maximums and means, and larger ranges, even when only the Mandarin high falling tone was compared with English. In contrast, for a prose passage, the two languages were more similar, differing only in the mean F0, Mandarin again being higher. The study thus contributes to the growing literature showing that languages can differ in their F0 profile, but highlights the fact that the choice of speech materials to compare can be critical.

Perception of pitch location within a speaker's range: fundamental frequency, voice quality and speaker sex.

How are listeners able to identify whether the pitch of a brief isolated sample of an unknown voice is high or low in the overall pitch range of that speaker? Does the speaker's voice quality convey crucial information about pitch level? Results and statistical models of two experiments that provide answers to these questions are presented. First, listeners rated the pitch levels of vowels taken over the full pitch ranges of male and female speakers. The absolute f0 of the samples was by far the most important determinant of listeners' ratings, but with some effect of the sex of the speaker. Acoustic measures of voice quality had only a very small effect on these ratings. This result suggests that listeners have expectations about f0s for average speakers of each sex, and judge voice samples against such expectations. Second, listeners judged speaker sex for the same speech samples. Again, absolute f0 was the most important determinant of listeners' judgments, but now voice quality measures also played a role. Thus it seems that pitch level judgments depend on voice quality mostly indirectly, through its information about sex. Absolute f0 is the most important information for deciding both pitch level and speaker sex.

Crystal Structure and Twisted Aggregates of Oxcarbazepine Form III.

Polymorphism and crystal habit play vital roles in dictating the properties of crystalline materials. Here, the structure and properties of oxcarbazepine (OXCBZ) form III are reported along with the occurrence of twisted crystalline aggregates of this metastable polymorph. OXCBZ III can be produced by crystallization from the vapor phase and by recrystallization from solution. The crystallization process used to obtain OXCBZ III is found to affect the pitch, with the most prominent effect observed from the sublimation-grown OXCBZ III material where the pitch increases as the length of aggregates increases. Sublimation-grown OXCBZ III follows an unconventional mechanism of formation with condensed droplet formation and coalescence preceding nucleation and growth of aggregates. A crystal structure determination of OXCBZ III from powder X-ray diffraction methods, assisted by crystal structure prediction (CSP), reveals that OXCBZ III, similar to carbamazepine form II, contains void channels in its structure with the channels, aligned along the c crystallographic axis, oriented parallel to the twist axis of the aggregates. The likely role of structural misalignment at the lattice or nanoscale is explored by considering the role of molecular and closely related structural impurities informed by crystal structure prediction.

EVALUATION OF IMMUNE FUNCTION IN TWO POPULATIONS OF GREEN SEA TURTLES (CHELONIA MYDAS) IN A DEGRADED VERSUS A NONDEGRADED HABITAT.

There is a strong correlation between degraded marine habitats and the prevalence of diseases such as green turtle fibropapillomatosis (GTFP) in coastal populations. In GTFP, small to large tumors grow on the turtle's soft tissues and shell, while internal nodules may also occur. The disease primarily affects juvenile green sea turtles (Chelonia mydas) that reside in nearshore waters. As a link has been shown between environmental pollution and immune suppression in a variety of animals, the objective of our research was to compare innate and adaptive immune responsiveness in green sea turtles from a severely degraded and a more pristine habitat, which differ greatly in rates of GTFP. We quantified phagocytosis by flow cytometry and performed in vitro stimulation analysis to measure activity of both the innate and adaptive immune systems in wild-caught Florida green turtles. Sea turtles from the degraded environment, both with and without visible cutaneous tumors, exhibited significantly reduced phagocytosis and stimulation indices than did those from the less polluted environment. Our results suggest that environmental factors may contribute to the development of GTFP and thus can impact the health of sea turtle populations.

Octadecyl chain-bearing PEGylated poly(propyleneimine)-based dendrimersomes: physicochemical studies, redox-responsiveness, DNA condensation, cytotoxicity and gene delivery to cancer cells.

Stimuli-responsive nanocarriers have become increasingly important for nucleic acid and drug delivery in cancer therapy. Here, we report the synthesis, characterization and evaluation of disulphide-linked, octadecyl (C18 alkyl) chain-bearing PEGylated generation 3-diaminobutyric polypropylenimine dendrimer-based vesicles (or dendrimersomes) for gene delivery. The lipid-bearing PEGylated dendrimer was successfully synthesized through in situ two-step reaction. It was able to spontaneously self-assemble into stable, cationic, nanosized vesicles, with low critical aggregation concentration value, and also showed redox-responsiveness in presence of a glutathione concentration similar to that of the cytosolic reducing environment. In addition, it was able to condense more than 70% of DNA at dendrimer: DNA weight ratios of 5 : 1 and higher. This dendriplex resulted in an enhanced cellular uptake of DNA at dendrimer: DNA weight ratios of 10 : 1 and 20 : 1, by up to 16-fold and by up to 28-fold compared with naked DNA in PC-3 and DU145 prostate cancer cell lines respectively. At a dendrimer: DNA weight ratio of 20 : 1, it led to an increase in gene expression in PC-3 and DU145 cells, compared with DAB dendriplex. These octadecyl chain-bearing, PEGylated dendrimer-based vesicles are therefore promising redox-sensitive drug and gene delivery systems for potential applications in combination cancer therapy.

Optical phonetics and visual perception of lexical and phrasal stress in English.

In a study of optical cues to the visual perception of stress, three American English talkers spoke words that differed in lexical stress and sentences that differed in phrasal stress, while video and movements of the face were recorded. The production of stressed and unstressed syllables from these utterances was analyzed along many measures of facial movement, which were generally larger and faster in the stressed condition. In a visual perception experiment, 16 perceivers identified the location of stress in forced-choice judgments of video clips of these utterances (without audio). Phrasal stress was better perceived than lexical stress. The relation of the visual intelligibility of the prosody of these utterances to the optical characteristics of their production was analyzed to determine which cues are associated with successful visual perception. While most optical measures were correlated with perception performance, chin measures, especially Chin Opening Displacement, contributed the most to correct perception independently of the other measures. Thus, our results indicate that the information for visual stress perception is mainly associated with mouth opening movements.

Camptothecin-based dendrimersomes for gene delivery and redox-responsive drug delivery to cancer cells.

Combination therapy involving chemotherapeutic drugs and genes is emerging as a promising strategy to provide a synergistic therapeutic effect, to overcome drug resistance while reducing the severe side effects associated with conventional chemotherapeutic drugs. However, the lack of nanomedicines able to simultaneously carry anti-cancer drugs and nucleic acids limits the application of this therapeutic strategy. To overcome this issue, we proposed to synthesize a pro-drug dendrimer by conjugating the PEGylated, positively charged generation 3-diaminobutyric polypropylenimine dendrimer to the anti-cancer drug camptothecin with a redox-sensitive disulphide linkage, and evaluate its efficacy to co-deliver the complexed DNA and camptothecin to cancer cells. This PEGylated pro-drug dendrimer was found to spontaneously self-assemble into cationic (∼3-5 mV) vesicles at pH 7.4, at a critical aggregation concentration of about 200 µg mL-1. These vesicles (dendrimersomes) became smaller (150-200 nm) with increasing dendrimer concentration and remained stable over 7 days. They were able to release about 70% of the conjugated camptothecin in presence of 50 mM glutathione (equivalent to the intracellular environment of tumor tissue). They could also condense more than 85% of the DNA at dendrimer : DNA weight ratios of 5 : 1 and higher. DNA condensation occurred instantly and was found to be stable for at least 24 h. This led to an enhanced cellular uptake of DNA (by up to 1.6-fold) and increased gene transfection (by up to 2.4-fold) in prostate cancer cells in comparison with the unmodified dendrimer. These novel dendrimersomes are therefore promising for single carrier-based combination cancer therapy.

Redox-sensitive, cholesterol-bearing PEGylated poly(propylene imine)-based dendrimersomes for drug and gene delivery to cancer cells.

Stimuli-responsive nanocarriers have attracted increased attention as materials that can facilitate drug and gene delivery in cancer therapy. The present study reports the development of redox-sensitive dendrimersomes comprising disulfide-linked cholesterol-bearing PEGylated dendrimers, which can be used as drug and gene delivery systems. Two disulfide-linked cholesterol-bearing PEGylated generation 3 diaminobutyric polypropylenimine dendrimers have been successfully synthesized via an in situ two-step reaction. They were able to spontaneously self-assemble into stable, cationic, nanosized vesicles (or dendrimersomes) with lower critical aggregation concentration values for high-cholesterol-bearing vesicles. These dendrimersomes were able to entrap both hydrophilic and hydrophobic dyes, and they also showed a redox-responsive sustained release of the entrapped guests in the presence of a glutathione concentration similar to that of a cytosolic reducing environment. The high-cholesterol-bearing dendrimersomes were found to have a higher melting enthalpy, increased adsorption tendency on mica surface, entrapping ability for a larger amount of hydrophobic drugs, and increased resistance to redox-responsive environments in comparison with their low-cholesterol counterpart. In addition, both dendrimersomes were able to condense more than 85% of the DNA at all the tested ratios for the low-cholesterol vesicles, and at dendrimer : DNA weight ratios of 1 : 1 and higher for the high-cholesterol vesicles. These vesicles resulted in an enhanced cellular uptake of DNA, by up to 15-fold when compared with naked DNA with low-cholesterol vesicles. As a result, they increased the gene transfection on the PC-3 prostate cancer cell line, with the highest transfection being obtained with low-cholesterol vesicle complexes at a dendrimer : DNA weight ratio of 5 : 1 and high-cholesterol vesicle complexes at a dendrimer : DNA weight ratio of 10 : 1. These transfection levels were about 5-fold higher than those observed when treated with naked DNA. These cholesterol-bearing PEGylated dendrimer-based vesicles are, therefore, promising as redox-sensitive drugs and gene delivery systems for potential applications in combination cancer therapies.

Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL, and interleukin-12.

The possibility of using gene therapy for the treatment of prostate cancer is limited by the lack of intravenously administered delivery systems able to safely and selectively deliver therapeutic genes to tumors. Given that lactoferrin (Lf) receptors are overexpressed on prostate cancer cells, we hypothesized that the conjugation of Lf to generation 3-diaminobutyric polypropylenimine dendrimer would improve its transfection and therapeutic efficacy in prostate cancer cells. In this study, we demonstrated that the intravenous administration of Lf-bearing DAB dendriplexes encoding TNFα resulted in the complete suppression of 70% of PC-3 and 50% of DU145 tumors over one month. Treatment with DAB-Lf dendriplex encoding TRAIL led to tumor suppression of 40% of PC-3 tumors and 20% of DU145 tumors. The treatment was well tolerated by the animals. Lf-bearing generation 3-polypropylenimine dendrimer is therefore a highly promising delivery system for non-viral gene therapy of prostate cancer.

Highly specific novel method for isolation and purification of lupus anti-DNA antibody via oligo-(dT) magnetic beads.

A novel method for isolation and purification of anti-ssDNA antibodies from human sera is developed. The process involves: antibody purification based on their affinity for single-stranded sequence of thymidines and removal of remaining components via protein G coated magnetic beads, with high affinity for only IgG subclass. The high degree of purity and molecular weights of healthy versus lupus anti-ssDNA antibodies were confirmed by SDS-PAGE and silver staining. Western blot confirmed IgG isotype. This novel technique allows for diagnostic purposes, structural and functional analysis of anti-DNA antibodies, and studies of their role in autoimmune diseases.

Isolation and Purification of Th9 Cells for the Study of Inflammatory Diseases in Research and Clinical Settings.

Th9 cells are associated with atopic and inflammatory diseases, and their increased levels and function correlate with the severity of symptoms in various inflammatory disorders including asthma, food allergy, atopic dermatitis, ulcerative colitis, and psoriatic arthritis. Thus, clinical trials are warranted to evaluate the role of Th9 cells in allergic diseases with the goal of controlling these ailments.Circulating T cells (naïve or memory CD4+ T cells) purified from human blood and expanded using anti-CD3 and anti-CD28 antibodies can be treated with appropriate cytokines in order to polarize them to the Th9 phenotype as evidenced by their production of IL-9. When treated in vitro with cholecalciferol or 1,25(OH)2 vitamin D3, cells polarized under Th9 conditions significantly downregulate production of IL-9. The percentage of polarized Th9 memory cells from patients treated with steroids or other modalities can be monitored during clinical trials and compared to control populations.

Effects of α-conotoxin ImI on TNF-α, IL-8 and TGF-ß expression by human macrophage-like cells derived from THP-1 pre-monocytic leukemic cells.

α7 nicotinic acetylcholine receptors (nAChRs) are ubiquitous in the nervous system and ensure important neurophysiological functionality for many processes. However, they are also found in cells of the immune system, where their role has been less studied. Here we report the pro-inflammatory effect of ImI, a well characterized conotoxin that inhibits α7 nAChRs, on differentiated THP-1 pre-monocyte macrophages (MDM) obtained by phorbol 12-myristate 13 acetate (PMA) treatment. Enzyme-linked immunosorbent assay (ELISA) performed on supernatant fluids of LPS challenged MDM showed ImI-mediated upregulation of pro-inflammatory cytokine TNF-α in an ImI concentration-dependent manner from 0.5 to 5.0 µmol/L and for IL-8 up to 1.0 µmol/L. Levels of anti-inflammatory cytokine TGF-ß remained practically unaffected in ImI treated MDMs. Nicotine at 10 µmol/L significantly downregulated the release of TNF-α, but showed a lesser effect on IL-8 secretion and no effect on TGF-ß. Fluorescent competitive assays involving ImI, α-bungarotoxin and nicotine using MDM and the murine macrophage RAW 264.7 suggest a common binding site in the α7 receptor. This work extends the application of conotoxins as molecular probes to non-excitatory cells, such as macrophages and supports the involvement of the α7 nAChR in regulating the inflammatory response via the cholinergic anti-inflammatory pathway (CAP).

Allergen induced pulmonary inflammation enhances mammary tumor growth and metastasis: Role of CHI3L1.

Metastasis is the primary cause of mortality in women with breast cancer. Metastasis to the lungs is greater in patients with pulmonary inflammatory illnesses. It is unknown how pre-existing pulmonary inflammation affects mammary tumor progression. We developed a novel breast cancer model in which pulmonary inflammation is induced in mice prior to tumor cell implantation. In the present study, we determined how pre-existing allergen-induced inflammation changes the pulmonary microenvironment to exacerbate tumor metastasis. We showed that pre-existing pulmonary inflammation in mammary tumor bearers is associated with: 1) an increase in growth of the primary tumor and metastasis; 2) an increase in the expression of a glycoprotein known as CHI3L1; and 3) increase in the levels of myeloid populations in their lungs. We also showed that myeloid derived cells from the lungs of allergic tumor bearers produce higher amounts of CHI3L1 than the saline controls. We previously showed that CHI3L1 induces the expression of proinflammatory and protumorigenic molecules. In this study, we show that CHI3L1 knockout tumor bearers with pre-existing allergic pulmonary inflammation had decreased levels of myeloid-derived cells, decreased levels of proinflammatory mediators, and a significant reduction in tumor volume and metastasis compared with the wild-type controls. Pre-existing inflammation and CHI3L1 might be driving the establishment of a premetastatic milieu in the lungs and aiding in the support of metastatic foci. Understanding the role of allergen-induced CHI3L1 and inflammation in tumor bearers and its effects on the pulmonary microenvironment could result in targeted therapies for breast cancer.