bluuebunny/crossref_metadata_2025 huggingface dataset:
Noise reduction in pipelines using Helmholtz resonators
Authors: Farooqui Maaz , Mekid Samir , Hawwa Muhammad , Aliuddin Atif , Al-Hamoud AbduAziz
Published: October 2011

Compressors are at the heart of most petrochemical and industrial power plants. They are usually the source of noise generation transmitted to pipelines. This noise is undesirable for people living close to installation and can also potentially cause structural failures in the piping. Particular attention is given to the modified solution using the Helmholtz resonator concept to reduce noise. An assessment of the noise reduction results using various types of resonators is carried out. A comparison between analytical, numerical simulation using COMSOL and experimental test is presented and discussed using a known patch-test.
The learnability of language-specific fundamental frequency-based rhythmic patterns
Authors: Yu Kristine M.
Published: October 2011

In addition to durational patterns, melodic patterns from variations in f0 contribute to percepts of speech rhythm, too (June 2005, Niebuhr 2009). The overall regularity of these melodic patterns is language-specific. In lexical tonal languages like Mandarin, f0 patterns may be quite variable, as many or all syllables may be associated with a tone; in stress-accent languages like English, f0 variation may be less variable as it is driven by stress and prosodic boundaries (Eady, 1982). In accentual phrase languages like Bengali and French, f0 variation is typically quite regular as it is driven almost entirely by prosodic boundaries in a very constrained way. With only acoustic parameters from the input available, are melodic patterns from these different kinds of languages learnable? And how is learnability affected if speech is directed to young infants? To study this, we recorded parents reading language samples in laboratory speech and in simulated infant directed speech in the languages mentioned above, and we are analyzing the speech with durational and f0 variability measures and prosodic (ToBI) labels. We will present results on learnability of melodic patterns using computational methods for pattern classification from a selection of the languages.
Weighting of prosodic cues in language discrimination by infants and adults
Authors: Vicenik Chad J. , Sundara Megha
Published: October 2011

Previous research has shown that infants and adults can discriminate between prosodically similar languages using only prosodic cues. These experiments were designed to determine whether listeners use pitch cues or segmental duration and timing cues (i.e., rhythm cues) in language discrimination. We tested American English learning 7-month-old infants and adults on their ability to discriminate between sentences in American English and German that had been re-synthesized to isolate different cues. Infants were presented with low-pass filtered speech and speech with re-synthesized sinusoidal pitch. Adults were presented with low-pass filtered speech and two conditions where sonorants were replaced with /a/ and obstruents were replaced with silence: one contained both pitch and durational cues and the other contained only durational cues. Pitch cues were important for infants as well as adults. For infants, pitch cues were necessary for successful language discrimination; neither segmental nor durational cues were sufficient. For adults, the presence of pitch prevented listeners from discriminating English and German. Only when pitch cues were removed did adults rely on durational differences to distinguish languages. These results demonstrate that to distinguish prosodically similar languages, specifically English and German, American English listeners' weight pitch cues over durational cues.
Rhythmic conversion between speakers of different dialects
Authors: Krivokapic Jelena
Published: October 2011

Speakers' convergence to each other's production of segments has been well established [Sancier and Fowler, J. Phon. 25, 421–426 (1995); Nielsen, J. Phon. 39, 132–142 (2011)]. Less is known about prosodic convergence, but it has been identified for stress and pitch accent [Krivokapic, JASA, 127, 1851 (2010); Krivokapic, JASA 129, 2658 (2011)]. In an acoustic experiment, rhythmic conversion between speakers of American and Indian English is examined. The two languages differ both in the stress patterns of individual lexical items and in their global rhythmic properties, with Indian English being syllable-timed and American English stress-timed. Changes in speakers' productions are examined using a synchronous speech task [Cummins, ARLO 3, 7–11 (2002), Zvonik and Cummins, Proc. Eurospeech 2003, 777–780 (2003)], where two speakers read sentences at the same time. Eight subjects (four dyads), each consisting of one Indian and one American speaker, read a short story that contained 12 words in which the two dialects differ in stress pattern and four sentences in which the global rhythmic properties are tested. The data of the dyad examined to date indicate convergence to a more stress-timed pattern for the Indian speaker.
Perceptually relevant information in energy above 5 kHz for speech and singing
Authors: Monson Brian B. , Vitela A. Davi , Story Brad H. , Lotto Andrew J.
Published: October 2011

Although high-frequency energy (HFE) is typically ignored in the speech perception and music literature, previous work has demonstrated that listeners are able to extract information from the structure of energy above 5 kHz. When exposed to HFE stimuli, listeners could accurately determine the mode of production (speech versus singing) and the gender of the speaker/singer. However, HFE in these previous experiments was presented in isolation at levels higher than what is typical of normal speech and singing. In the series of experiments presented here, the stimuli were presented at more appropriate levels. Additionally, speech-shaped masking noise from 0 to 5.6kHz (set at the mean levels for an average speaker/singer) was used to determine if HFE is usable by listeners even in the presence of masking by the more intense energy below 5 kHz in typical speech/voice listening conditions. Results indicate that even when the HFE stimuli are presented at typical levels and in the presence of a masker, listeners are still able to discriminate production modes and gender. These results suggest that HFE contains information that normal-hearing listeners can potentially access during the perception of speech and singing. [Work supported by NIH-NIDCD.]
Perceptual benefits of English coda-stop glottalization
Authors: Garellek Marc
Published: October 2011

Glottalized stops in codas (e.g., [t]) are commonly found in English, often when the coda-stop is unreleased. Glottalized phonation is known to increase the amplitudes of higher harmonics in the spectrum, possibly due to faster closing velocity of the vocal folds (Stevens, 1977). This suggests that glottalized phonation occurring before an unreleased stop may be useful to the listener for perceiving the formant transitions into the stop, because the higher frequencies will be amplified during glottalized phonation leading into the glottalized stop. To test this hypothesis, a phoneme monitoring task was conducted with native English speakers, who were asked to monitor for /t/ in onsets and codas of English words. The target stimuli were monosyllables ending in a coda-/t/, e.g., /bit/. All the stimuli were uttered by a phonetically trained speaker and varied according to whether the word was glottalized and/or ended in an unreleased stop. Preliminary results from the listeners' data suggest that their reaction time is faster for glottalized coda-/t/ (whether released or not), and that their detection accuracy improves when the coda-stop is both released and glottalized. Discussion will involve whether glottalization is a cue to formant transitions in general or to the presence of /t/ specifically.
Investigating the effect of speech stimuli on temporal masking release
Authors: Davies-Venn Evelyn , Nelson Peggy , Nie Yingjiu , Svec Adam , Bhagyashree Katare
Published: October 2011

The effect of masking release is still the source of numerous active investigations. However, differences in findings are sometimes noted among studies, especially related to potential gate frequency effects. The present study investigated the effect of masking release on listeners using a variety of speech materials . The main goal of this study was to investigate the effect of speech material on measures of masking release for listeners with normal hearing and hearing loss. The test stimuli were IEEE sentences and modified spondee words. To eliminate confounds of audibility and duration, the test stimuli were equated for duration and audibility. Listeners were tested across a wide range of audibility and gate frequencies. Performance and masking release results will be presented for these speech stimuli. [Work supported by NIDCD 008306.]
English speakers' discrimination of Korean plain versus aspirated affricates
Authors: Maye Jessica , Luque Jenna Silver
Published: October 2011

The Korean three-way voicing distinction has been of much interest to phoneticians. Korean obstruents may be plain, tense, or aspirated, which differ in VOT, closure duration, and f0 of vowel onset (Cho et al., 2002; Kim, 1994). Previous research on Korean stops has shown that English speakers perceive all three categories as voiceless in initial position (Shin, 2001). The present study extends this to Korean affricates, which are partly cued by frication duration, an acoustic cue that is distinctive in English for differentiating fricatives from affricates (Repp et al., 1978). Twenty monolingual English speakers participated in the study. The stimuli were six tokens each of the plain and aspirated Korean affricates ([tSa] and [tSha]), naturally produced by a male native speaker of Seoul Korean. Participants completed an AX discrimination task, following five practice trials in which they received feedback on their answers. Results showed very poor discrimination that did not differ from chance (mean d′ = 0.892; p < 0.001). These results indicate that despite the relevance of an additional acoustic cue that is distinctive in English (frication duration), the Korean contrast between plain versus aspirated affricates is difficult for English speakers to discriminate, paralleling previous research on Korean stops.
Non-native Japanese learners' perception of vowel length contrasts in Arabic and Japanese
Authors: Tsukada Kimiko
Published: October 2011

This study examined the perception of short vs. long vowel contrasts in Arabic and Japanese by four groups of listeners differing in their linguistic backgrounds: native Arabic (NA), native Japanese (NJ), non-native Japanese (NNJ), and Australian English (OZ) speakers. Listeners' first languages differed in the extent to which vowel duration is used contrastively. In both Arabic and Japanese, vowel length is phonemic. English, on the other hand, utilizes vowel duration in a more limited way. Of interest was the discrimination accuracy of NNJ listeners who learned Japanese as a second language beyond childhood. As expected, the NA and NJ groups discriminated their native contrasts more accurately than all the other groups while the NNJ listeners showed a significant shift in their perceptual behavior and outperformed the OZ listeners who had no knowledge of Japanese in discriminating the Japanese vowel length contrasts. Furthermore, NNJ was the only group who showed a balanced pattern of discrimination accuracy in Arabic and Japanese. Taken together, the results obtained in this study suggest that NNJ learned to discriminate Japanese vowel length contrasts to some extent, but the learning did not carry over cross-linguistically to the processing of vowel length contrasts in an unknown language, Arabic.
Effect of vowel height and nasal coda on Mandarin tone perception by second language learners
Authors: Lai Tzu-Yun , Su Yi-Wen
Published: October 2011

The present study aims to investigate whether second language (L2) learners of Mandarin will be affected by vowel height sequences and post-vocalic nasals in perceiving Mandarin tones. A total of 101 stimuli from a female native speaker of Mandarin were recorded for constructing the main experiment. Eight Mandarin L2 learners and two native speakers were recruited. The result indicated that L2 learners had a higher error rate when perceiving H-L-H (high-low-high) and nasal coda. However, perceiving H-L (high-low) or L-H (low-high) in tone 2 and tone 3, L2 learners easily mix up these together.
Listeners retune phoneme boundaries across languages
Authors: Reinisch Eva , Weber Andrea , Mitterer Holger
Published: October 2011

Listeners can flexibly retune category boundaries of their native language to adapt to non-canonically produced phonemes. This only occurs, however, if the pronunciation peculiarities can be attributed to stable and not transient speaker-specific characteristics. Listening to someone speaking a second language, listeners could attribute non-canonical pronunciations either to the speaker or to the fact that she is modifying her categories in the second language. We investigated whether, following exposure to Dutch-accented English, Dutch listeners show effects of category retuning during test where they hear the same speaker speaking her native language, Dutch. Exposure was a lexical-decision task where either word-final [f] or [s] was replaced by an ambiguous sound. At test listeners categorized minimal word pairs ending in sounds along an [f]-[s] continuum. Following exposure to English words, Dutch listeners showed boundary shifts of a similar magnitude as following exposure to the same phoneme variants in their native language. This suggests that production patterns in a second language are deemed a stable characteristic. A second experiment suggests that category retuning also occurs when listeners are exposed to and tested with a native speaker of their second language. Listeners thus retune phoneme boundaries across languages.
Spanish learners' perception of American and Southern British English vowels
Authors: Escudero Paola , Chladkova Katerina
Published: October 2011

Second-language (L2) studies show that learners differ in their vowel perception patterns, which can be attributed to their L2 proficiency or to different initial stages at the onset of L2 learning. The present study assessed the L2 perception of Southern British English (SBE) and American English (AE) vowels in 196 Spanish learners of English with different general comprehension proficiencies. Escudero and Chladkova (2010) showed that naive Spanish listeners perceived AE vowels differently than SBE vowels. The current results show that L2 learners' performance matches that of naive listeners. For instance, learners identified AE /ae/ correctly in only 3% of the time, as opposed to 32% for the same SBE vowel. This is because naive listeners assimilate AE /ae/ to Spanish /e/, which is the same native vowel they choose for AE /I/ and /E/, while SBE /ae/ is mostly assimilated to Spanish /a/. In addition, there was a significant effect of L2 proficiency on vowel identification accuracy and on the use of vowel duration. More proficient learners identified L2 vowels more accurately and used duration in a more native-like way than less proficient learners. Implications of our findings for models of L2 speech perception are discussed.
Perception of the proximal voice features for emotional speech
Authors: Patel Sona , Banzigar Tanja , Scherer Klaus R.
Published: October 2011

The expression of emotions results in a number of changes to the acoustic signal. Considering that prosodic events may be encoded into the speech signal using multiple acoustic features, many acoustic variations may be redundant for listeners. An understanding of the acoustic changes that listeners can reliably use to differentiate emotional speech will help in the modeling emotions, for example, from a Brunswikian perspective. In the Brunswikian model of emotion communication, the acoustic features are represented as “distal cues” and the subjective perception of these changes are represented as “proximal percepts.” Few attempts have been made to understand the proximal percepts of emotional speech in relation to the acoustic properties they represent. In this study, 19 listeners were asked to rate a set of 160 samples (2 sentences expressed in 8 emotions by 10 speakers) using 12 visual-analog scales (8 prosodic scales and 4 emotion dimensions). Results showed high reliability for all scales except roughness, articulation, and intonation. The emotions were especially differentiated on the dimensions of loudness, sharpness, and speech rate. Regression analysis was used to determine the underlying acoustic cues represented by these scales. The results of this analysis will be discussed.
Cross-language perception of Brazilian Portuguese vowels by Californian English listeners
Authors: Vasiliev Polina , Escudero Paola
Published: October 2011

The present study investigates the perceptual assimilation and auditory categorization of Brazilian Portuguese vowels by monolingual speakers of Californian English. In the perceptual assimilation task, listeners classified 140 vowel tokens in terms of 10 native English vowel categories by choosing from written English words containing the vowels. The stimuli were isolated vowels extracted from nonce words produced by 10 male and 10 female native speakers of Brazilian Portuguese. In the auditory categorization task, the same listeners identified six Portuguese vowel contrasts which were presented in an XAB format, where X were a subset of the same natural vowel tokens from the previous task and A and B were synthesized prototypes of the Portuguese vowels. The results of the perceptual assimilation task demonstrate that Californian English listeners assimilate two out of six Portuguese vowel contrasts to more than two native vowel categories, resulting in many instances of multiple category assimilation (MCA). In the auditory categorization task, most of the contrasts with the lowest accuracy were those that showed MCA, which demonstrates that this pattern of assimilation may be the cause of Californian English listeners' perceptual difficulties with Portuguese vowels. Predictions for L2 acquisition are made.
Training Korean listeners to perceive phonemic length contrasts in Japanese: Effects of speaking rate variation and contrast type
Authors: Sonu Mee , Tajima Keiichi , Kato Hiroaki , Sagisaka Yoshinori
Published: October 2011

Japanese phonemic length contrasts are difficult to perceive for native-Korean listeners learning Japanese as a second language (L2). Aiming at an effective L2 training method for L2 learners, two experiments were conducted. Experiment 1 evaluated which acoustic cues Korean listeners rely on when categorizing the phonemic length contrast. Experiment 2 examined how differences in speaking rate variation (slow, normal, and fast) and contrast type (vowel contrast vs. consonant contrast) would affect the effectiveness of perceptual training, using a minimal-pair identification task with words embedded in carrier sentences. There were four training conditions comprising combinations of two contrast types (vowel or consonant length) and two speaking-rate variations (single rate or three different rates). Results show that L2 listeners exploit absolute segmental duration to identify phonemic length contrast rather than durational criteria that vary according to speaking rate. Moreover, the trained groups significantly improved in their overall accuracy after training. However, none of the training groups showed significant generalization to untrained contrast types. These results suggest that the effect of training is limited and does not generalize to untrained contrast types even when speaking rate variation is incorporated during training. [Work supported in part by the Grant-in-Aid for Scientific Research (B), JSPS.]
Acoustical Society of America Distinguished Service Citation
Authors: Stern Richard
Published: October 2011

The Distinguished Service Citation is awarded to a present or former member of the Society in recognition of outstanding service to the Society.
Acoustical Society of America Trent-Crede Medal
Authors: Stepanishen Peter R.
Published: October 2011

The Trent-Crede Medal is presented to an individual, irrespective of nationality, age, or society affiliation, who has made an outstanding contribution to the science of mechanical vibration and shock, as evidenced by publication of research results in professional journals or by other accomplishments in the field.
Comment on “Changes in Climatic Water Balance Drive Downhill Shifts in Plant Species’ Optimum Elevations”
Authors: Stephenson Nathan L. , Das Adrian J.
Published: October 2011

Crimmins
et al
. (Reports, 21 January 2011, p. 324) attributed an apparent downward elevational shift of California plant species to a precipitation-induced decline in climatic water deficit. We show that the authors miscalculated deficit, that the apparent decline in species’ elevations is likely a consequence of geographic biases, and that unlike temperature changes, precipitation changes should not be expected to cause coordinated directional shifts in species’ elevations.
Observation of Correlated Particle-Hole Pairs and String Order in Low-Dimensional Mott Insulators
Authors: Endres M. , Cheneau M. , Fukuhara T. , Weitenberg C. , Schauß P. , Gross C. , Mazza L. , Bañuls M. C. , Pollet L. , Bloch I. , Kuhr S.
Published: October 2011

Parity correlations in a one-dimensional Bose gas in an optical lattice reveal a hidden “string order.”
The Antibacterial Lectin RegIIIγ Promotes the Spatial Segregation of Microbiota and Host in the Intestine
Authors: Vaishnava Shipra , Yamamoto Miwako , Severson Kari M. , Ruhn Kelly A. , Yu Xiaofei , Koren Omry , Ley Ruth , Wakeland Edward K. , Hooper Lora V.
Published: October 2011

Innate immune signaling and antimicrobial peptide activity maintain separation of the microbiota and intestinal epithelium.
Early Gamma Oscillations Synchronize Developing Thalamus and Cortex
Authors: Minlebaev Marat , Colonnese Matthew , Tsintsadze Timur , Sirota Anton , Khazipov Roustem
Published: October 2011

Thalamic gamma rhythms help develop highly spatially and laminar-specific ascending cortical projections.
Peruvian Highlands, Fume-Free
Authors: Bodereau Pilar Nores
Published: October 2011

In the andean highlands of Peru, a typical single-room home will burn approximately 3.6 tons of wood a year, not just for heating but for cooking indoors. Three billion people world-wide cook indoors over open fires with solid fuels. This use has a detrimental effect on human health. According to the World Health Organization (WHO), nearly two million people die annually from open-fire cooking, with women and young children the most affected. The hazards related to these practices include acute respiratory infections, insufficient weight at birth, and chronic obstructive pulmonary disease. Despite WHO estimates that cookstove smoke is one of the top five threats to public health in poor developing countries, the effects of exposure to it have received limited funding and research attention. The good news is that since the announcement last year of the Global Alliance for Clean Cookstoves [launched by the United Nations (UN) Foundation], coordinated efforts are successfully under way to support the use of clean cookstoves in the developing world.
*
Social Psychology and Social Change
Redirect
The Surprising New Science of Psychological Change

by Timothy D. Wilson

Little, Brown, New York, 2011. 287 pp. $25.99, C$28.99. ISBN 9780316051880.
Authors: Cohen Geoffrey L.
Published: October 2011

Weighing contributions of social psychology to understanding and remedying social problems, Wilson argues that the key to transforming people's lives lies in their learning to recast the stories they tell themselves.
Grass Trumps Trees with Fire
Authors: Mayer Audrey L. , Khalyani Azad Henareh
Published: October 2011

Feedbacks involving rainfall, fire, and vegetation govern transitions between forests, savannas, and grasslands.
Panel Draws Ambitious Road Map for Gulf Restoration
Authors: Malakoff David
Published: October 2011

A presidential task force is calling for dramatically expanding efforts to restore battered Gulf of Mexico ecosystems—and using billions of dollars in fines resulting from the 2010
Deepwater Horizon
oil spill to pay for them.
Teasing Out Cause and Effect in Macroeconomics
Authors: Bhattacharjee Yudhijit
Published: October 2011

Christopher Sims and Thomas Sargent have won this year's Nobel Prize in economics for sorting out the tangles of cause and effect in the world of macroeconomics.
African Data Bolster New View of Modern Human Origins
Authors: Gibbons Ann
Published: October 2011

Two papers have independently suggested that early
Homo sapiens
interbred with now-extinct forms of humans in Africa, so that some living Africans carry genes from archaic people, just as all Europeans and Asians recently have been shown to do.
Gut Bacteria Lend a Molecular Hand to Viruses
Authors: Pennisi Elizabeth
Published: October 2011

Two reports in this week's issue of
Science
describe viruses that co-opt components of the gut microflora to establish infection.
Vital Details of Global Warming Are Eluding Forecasters
Authors: Kerr Richard A.
Published: October 2011

Decision-makers need to know how to prepare for inevitable climate change, but climate researchers are still struggling to sharpen their fuzzy picture of what the future holds.
Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption
Authors: Schuerman L. , Wysocki J. , Tejedor J. C. , Knuf M. , Kim K.-H. , Poolman J.
Published: October 2011

We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines.
A Combination Vaccine Consisting of Three Live Attenuated Enterotoxigenic Escherichia coli Strains Expressing a Range of Colonization Factors and Heat-Labile Toxin Subunit B Is Well Tolerated and Immunogenic in a Placebo-Controlled Double-Blind Phase I Trial in Healthy Adults
Authors: Harro Clayton , Sack David , Bourgeois A. Louis , Walker R. , DeNearing Barbara , Feller Andrea , Chakraborty Subhra , Buchwaldt Charlotte , Darsley Michael J.
Published: October 2011

Immune responses against colonization factors (CFs) and the nontoxic B component of the enterotoxigenic
Escherichia coli
(ETEC) heat-labile toxin (LTB) are considered to be important for immunity against diarrhea caused by ETEC. Individual live attenuated ETEC derivatives that have had their toxin genes removed and whose
aroC
,
ompC
, and
ompF
genes are deleted have shown promise as vaccines against ETEC. The development of such strains has culminated in the testing of a three-strain-combination live attenuated vaccine known as ACE527, comprised of strains ACAM2025 expressing colonization factor antigen I (CFA/I) and LTB; ACAM2022, expressing CS5, CS6, and LTB; and ACAM2027, expressing CS1, CS2, CS3, and LTB. The recombinant CF and LTB genes expressed in the three strains were inserted into the bacterial chromosome to ensure their stable inheritance and expression without the requirement for any selection. ACE527 has been tested in a randomized placebo-controlled, double-blind, phase I safety and immunogenicity study in healthy adult volunteers and proved to be well tolerated and immunogenic at dose levels of 10
10
and 10
11
total CFU. There was no indication of strain interference on the basis of fecal shedding patterns, with all three being detected in the feces of 50% and 83% of low- and high-dose vaccine recipients, respectively. Similarly, strong immune responses to LTB and to CFs expressed on all three constituent strains were induced, with at least 50% of subjects in the high-dose group responding to LTB, CFA/I, CS3, and CS6.
Clinical Performance of the (1,3)-β-
d
-Glucan Assay in Early Diagnosis of Nosocomial Candida Bloodstream Infections
Authors: Del Bono Valerio , Delfino Emanuele , Furfaro Elisa , Mikulska Malgorzata , Nicco Elena , Bruzzi Paolo , Mularoni Alessandra , Bassetti Matteo , Viscoli Claudio
Published: October 2011

Microbiological diagnosis of nosocomial candidemia is negatively affected by suboptimal culture yield. Alternative methods are not fully reliable as an aid in candidemia diagnosis. Recently, the detection of (1,3)-β-
d
-glucan (BG) has been shown to be very promising in this setting. We carried out a prospective study on the clinical usefulness of BG detection in early diagnosis of candidemia. BG detection was performed in patients with fever unresponsive to antibacterial agents and risk factors for candidemia. BG detection was done with the Fungitell test. A total of 152 patients were included in the study; 53 were proven to have candidemia, while in 52 patients candidemia was excluded on microbiological and clinical bases. The remaining 47 patients were considered to have possible candidemia. In summary, 41 of 53 candidemia patients (77.3%), 9 of 52 patients without candidemia (17.3%), and 38 of 47 patients with possible candidemia (80.8%) were positive in the BG assay. With these results, the sensitivity and the specificity of the assay were 77% and 83%, respectively. BG levels of >160 pg/ml were highly predictive of candidemia. In 36 of 41 patients with candidemia and positive BG testing, the BG assay was performed within 48 h from when the first
Candida-
positive blood sample for culture was drawn, thus allowing a possible earlier start of antifungal therapy. Based on these results, the BG assay may be used as an aid in the diagnosis of nosocomial candidemia. The timing of assay performance is critical for collecting clinically useful information. However, the test results should be associated with clinical data.
Comparison of the FilmArray Respiratory Panel and Prodesse Real-Time PCR Assays for Detection of Respiratory Pathogens
Authors: Loeffelholz M. J. , Pong D. L. , Pyles R. B. , Xiong Y. , Miller A. L. , Bufton K. K. , Chonmaitree T.
Published: October 2011

We compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the FilmArray Respiratory Panel (RP) multiplex PCR assay (Idaho Technology, Inc., Salt Lake City, UT) with those of the Food and Drug Administration (FDA)-cleared Prodesse ProFlu+, ProFAST+, ProParaflu+, Pro hMPV+, and ProAdeno+ real-time PCR assays (Gen-Probe, San Diego, CA). The assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children under 1 year of age with upper respiratory tract symptoms. To resolve discordant results and confirm pathogens detected only by the larger FilmArray panel, we performed laboratory-developed real-time PCR assays. Among viruses detectable by both commercial assays (adenovirus, human metapneumovirus, influenza A virus, influenza B virus, parainfluenza viruses 1 to 3, and respiratory syncytial virus), the FilmArray and Prodesse assays showed good overall agreement (181/192 [94.3%]; kappa = 0.87; 95% CI, 0.79 to 0.94). FilmArray RP detected more parainfluenza viruses 1 and 3 than ProParaflu+ (18 versus 13) while ProAdeno+ detected more adenoviruses (11 versus 6), but these differences were not statistically significant. Additionally, FilmArray RP detected 138 pathogens (confirmed as true positives) not included in the Prodesse assays (rhinovirus [RV]/enterovirus [EV], 118; bocavirus, 8; coronavirus, 7; parainfluenza virus 4, 4;
Mycoplasma pneumoniae
, 1). FilmArray RP was cleared by the FDA following the completion of this study. The FDA-cleared version includes the following targets: adenovirus, coronaviruses HKU1 and NL63, human metapneumovirus (hMPV), influenza A virus (to type level only), influenza A H1 seasonal virus, influenza A H3 seasonal virus, influenza A virus H1-2009, influenza B virus, parainfluenza viruses 1 to 4, respiratory syncytial virus (RSV), and RV/EV (no differentiation). The larger panel in the FilmArray RP assay allowed the detection of additional respiratory pathogens compared to the Prodesse assays. In this population of young children with upper respiratory tract infection, RV/EV accounted for the majority of the additional pathogens detected by FilmArray RP.
Characterization of Genetic Diversity of Bacillus anthracis in France by Using High-Resolution Melting Assays and Multilocus Variable-Number Tandem-Repeat Analysis
Authors: Derzelle S. , Laroche S. , Le Flèche P. , Hauck Y. , Thierry S. , Vergnaud G. , Madani N.
Published: October 2011

Using high-resolution melting (HRM) analysis, we developed a cost-effective method to genotype a set of 13 phylogenetically informative single-nucleotide polymorphisms (SNPs) within the genome of
Bacillus anthracis
. SNP discrimination assays were performed in monoplex or duplex and applied to 100
B. anthracis
isolates collected in France from 1953 to 2009 and a few reference strains. HRM provided a reliable and cheap alternative to subtype
B. anthracis
into one of the 12 major sublineages or subgroups. All strains could be correctly positioned on the canonical SNP (canSNP) phylogenetic tree, except the divergent Pasteur vaccine strain ATCC 4229. We detected the cooccurrence of three canSNP subgroups in France. The dominant B.Br.CNEVA sublineage was found to be prevalent in the Alps, the Pyrenees, the Auvergne region, and the Saône-et-Loire department. Strains affiliated with the A.Br.008/009 subgroup were observed throughout most of the country. The minor A.Br.001/002 subgroup was restricted to northeastern France. Multiple-locus variable-number tandem-repeat analysis using 24 markers further resolved French strains into 60 unique profiles and identified some regional patterns. Diversity found within the A.Br.008/009 and B.Br.CNEVA subgroups suggests that these represent old, ecologically established clades in France. Phylogenetic relationships with strains from other parts of the world are discussed.
Xpert MTB/RIF Assay for Diagnosis of Pleural Tuberculosis
Authors: Friedrich Sven O. , von Groote-Bidlingmaier Florian , Diacon Andreas H.
Published: October 2011

We prospectively investigated the diagnostic utility of the Xpert MTB/RIF (
Mycobacterium tuberculosis
/rifampin [RIF] resistance) assay in 20 cases with confirmed tuberculous pleural effusion. The sensitivity and specificity of the Xpert assay in pleural fluid were 25% and 100%, respectively. All cases positive by the Xpert assay were also positive by pleural fluid culture.
Circulating MicroRNAs in Patients with Active Pulmonary Tuberculosis
Authors: Fu Yurong , Yi Zhengjun , Wu Xiaoyan , Li Jianhua , Xu Fuliang
Published: October 2011

Emerging evidence shows that microRNAs (miRNAs) play an important role in pathogen-host interactions. Circulating miRNAs have been repeatedly and stably detected in blood and hold promise to serve as molecular markers for diverse physiological and pathological conditions. To date, the relationship between circulating miRNAs and active pulmonary tuberculosis (TB) has not been reported. Using microarray-based expression profiling followed by real-time quantitative PCR validation, the levels of circulating miRNAs were compared between patients with active pulmonary tuberculosis and matched healthy controls. The receiver operating characteristic curve was used to evaluate the diagnostic effect of selected miRNA. Bioinformatic analysis was used to explore the potential roles of these circulating miRNAs in active pulmonary tuberculosis infection. Among 92 miRNAs significantly detected, 59 miRNAs were downregulated and 33 miRNAs were upregulated in the TB serum compared to their levels in the control serum. Interestingly, only two differentially expressed miRNAs were increased not only in the serum but also in the sputum of patients with active pulmonary tuberculosis compared to the levels for the healthy controls. Upregulated miR-29a could discriminate TB patients from healthy controls with reasonable sensitivity and specificity. A number of significantly enriched pathways regulated by these circulating miRNAs were predicted, and most of them were involved in acute-phase response, inflammatory response, and the regulation of the cytoskeleton. In all, for the first time our results revealed that a number of miRNAs were differentially expressed during active pulmonary tuberculosis infection, and circulating miR-29a has great potential to serve as a marker for the detection of active pulmonary tuberculosis infection.
Species Identification of Clinical Isolates of Anaerobic Bacteria: a Comparison of Two Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Systems
Authors: Justesen Ulrik Stenz , Holm Anette , Knudsen Elisa , Andersen Line Bisgaard , Jensen Thøger Gorm , Kemp Michael , Skov Marianne Nielsine , Gahrn-Hansen Bente , Møller Jens Kjølseth
Published: October 2011

We compared two matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) systems (Shimadzu/SARAMIS and Bruker) on a collection of consecutive clinically important anaerobic bacteria (
n
= 290). The Bruker system had more correct identifications to the species level (67.2% versus 49.0%), but also more incorrect identifications (7.9% versus 1.4%). The system databases need to be optimized to increase identification levels. However, MALDI-TOF MS in its present version seems to be a fast and inexpensive method for identification of most clinically important anaerobic bacteria.
Performance of the MGIT TBc Identification Test and Meta-Analysis of MPT64 Assays for Identification of the Mycobacterium tuberculosis Complex in Liquid Culture
Authors: Brent Andrew J. , Mugo Daisy , Musyimi Robert , Mutiso Agnes , Morpeth Susan , Levin Michael , Scott J. Anthony G.
Published: October 2011

Rapid MPT64-based immunochromatographic tests (MPT64 ICTs) have been developed to detect
Mycobacterium tuberculosis
complex (MTBC) in culture. We demonstrated the noninferiority of one commercial MTP64 ICT, the MGIT TBc identification (TBcID) test, to GenoType line probe assays for MTBC identification in positive MGIT cultures. Meta-analysis of MPT64 ICT performance for identification of MTBC in liquid culture confirmed similar very high sensitivities and specificities for all three commercial MPT64 assays for which sufficient data were available.
Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation
Authors: Nam Jeong-Hyun , Kim Eun-Ha , Song Daesub , Choi Young Ki , Kim Jeong-Ki , Poo Haryoung
Published: October 2011

The migratory waterfowl of the world are considered to be the natural reservoir of influenza A viruses. Of the 16 hemagglutinin subtypes of avian influenza viruses, the H6 subtype is commonly perpetuated in its natural hosts and is of concern due to its potential to be a precursor of highly pathogenic influenza viruses by reassortment. During routine influenza surveillance, we isolated an unconventional H6N5 subtype of avian influenza virus. Experimental infection of mice revealed that this isolate replicated efficiently in the lungs, subsequently spread systemically, and caused lethality. The isolate also productively infected ferrets, with direct evidence of contact transmission, but no disease or transmission was seen in pigs. Although the isolate possessed the conserved receptor-binding site sequences of avian influenza viruses, it exhibited relatively low replication efficiencies in ducks and chickens. Our genetic and molecular analyses of the isolate revealed that its PB1 sequence showed the highest evolutionary relationship to those of highly pathogenic H5N1 avian influenza viruses and that its PA protein had an isoleucine residue at position 97 (a representative virulence marker). Further studies will be required to examine why our isolate has the virologic characteristics of mammalian influenza viruses but the archetypal receptor binding profiles of avian influenza viruses, as well as to determine whether its potential virulence markers (PB1 analogous to those of H5N1 viruses or isoleucine residue at position 97 within PA) could render it highly pathogenic in mice.
A Virion-Associated Protein Kinase Induces Apoptosis
Authors: Chitnis Nilesh S. , Paul Eric R. , Lawrence Paulraj K. , Henderson Curtis W. , Ganapathy Saranya , Taylor Patrick V. , Virdi Kamaldeep S. , D’Costa Susan M. , May Ashley R. , Bilimoria Shan L.
Published: October 2011

Apoptosis and inhibition of host gene expression are often associated with virus infections. Many viral polypeptides modulate apoptosis by direct interaction with highly conserved apoptotic pathways. Some viruses induce apoptosis during late stages of the infection cycle, while others inhibit apoptosis to facilitate replication or maintain persistent infection. In previous work, we showed that Chilo iridescent virus (CIV) or CIV virion protein extract induces apoptosis in spruce budworm and cotton boll weevil cell cultures. Here, we characterize the product of a CIV gene (
iridovirus
serine/threonine kinase;
istk
) with signature sequences for S/T kinase and ATP binding. ISTK appears to belong to the superfamily, vaccinia-related kinases (VRKs). The
istk
gene was expressed in
Pichia pastoris
vectors. Purified ISTK (48 kDa) exhibited S/T kinase activity. Treatment with ISTK induced apoptosis in budworm cells. A 35-kDa cleavage product of ISTK retaining key signature sequences was identified during purification.
Pichia
-expressed 35-kDa polypeptide, designated iridoptin, induced apoptosis and inhibition of host protein synthesis in budworm and boll weevil cells. A mutation in the ATP-binding site eliminated both kinase and apoptosis activity of iridoptin, suggesting that kinase activity is essential for induction of apoptosis. Analysis with custom antibody confirmed that ISTK is a structural component of CIV particles. This is the first demonstration of a viral kinase inducing apoptosis in any virus-host system and the first identification of a factor inducing apoptosis or host protein shutoff for the family
Iridoviridae
.
Characterization of the Pleiotropic Effects of the Genotype G-Specific 36-Nucleotide Insertion in the Context of Other Hepatitis B Virus Genotypes
Authors: Gutelius Danielle , Li Jisu , Wands Jack , Tong Shuping
Published: October 2011

The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves as the messenger for both core and P proteins, with the downstream P gene translated by ribosomal leaky scanning. HBV replication begins with packaging of the pgRNA and P protein into core protein particles, followed by conversion of RNA into DNA. Genotype G has a low replication capacity due to a low pgRNA level. It has a 36-nucleotide (nt) insertion in the 5′ end of the core gene, adding 12 residues to the core protein. The insertion is needed to maintain efficient core protein expression and genome replication but causes inefficient virion secretion yet high maturity of virion DNA. In the present study, we confirmed that the 36-nt insertion had similar effects on core protein expression and virion secretion when it was introduced into genotype A and D clones but no impact on virion genome maturity. Surprisingly, the insertion impaired genome replication in both genotypes. Transcomplementation assays suggest that increased efficiency of core protein translation diminishes ribosomal scanning toward the downstream P gene. Indeed, mutating the core gene Kozak sequence restored core protein to lower levels but increased replication of the insertion mutant. Similar mutations impaired replication in genotype G. On the other hand, replacement of the core promoter sequence of genotype G with genotype A sequence increased pgRNA transcription and genome replication, implicating this region in the low replication capacity of genotype G. Why the 36-nt insertion is present in genotype G but absent in other genotypes is discussed.
A Virus-Like Particle-Based Epstein-Barr Virus Vaccine
Authors: Ruiss Romana , Jochum Simon , Wanner Gerhard , Reisbach Gilbert , Hammerschmidt Wolfgang , Zeidler Reinhard
Published: October 2011

Epstein-Barr Virus (EBV) is an ubiquitous human herpesvirus which can lead to infectious mononucleosis and different cancers. In immunocompromised individuals, this virus is a major cause for morbidity and mortality. Transplant patients who did not encounter EBV prior to immunosuppression frequently develop EBV-associated malignancies, but a prophylactic EBV vaccination might reduce this risk considerably. Virus-like particles (VLPs) mimic the structure of the parental virus but lack the viral genome. Therefore, VLPs are considered safe and efficient vaccine candidates. We engineered a dedicated producer cell line for EBV-derived VLPs. This cell line contains a genetically modified EBV genome which is devoid of all potential viral oncogenes but provides viral proteins essential for the assembly and release of VLPs via the endosomal sorting complex required for transport (ESCRT). Human B cells readily take up EBV-based VLPs and present viral epitopes in association with HLA molecules to T cells. Consequently, EBV-based VLPs are highly immunogenic and elicit humoral and strong CD8+and CD4+T cell responsesin vitroand in a preclinical murine modelin vivo. Our findings suggest that VLP formulations might be attractive candidates to develop a safe and effective polyvalent vaccine against EBV.
Pyrosequencing Reveals Restricted Patterns of CD8+T Cell Escape-Associated Compensatory Mutations in Simian Immunodeficiency Virus
Authors: Burwitz Benjamin J. , Sacha Jonah B. , Reed Jason S. , Newman Laura P. , Norante Francesca A. , Bimber Benjamin N. , Wilson Nancy A. , Watkins David I. , O'Connor David H.
Published: October 2011

CD8+T cells play a major role in the containment of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. CD8+T cell-driven variations in conserved regions under functional constraints result in diminished viral replicative capacity. While compensatory mutations outside an epitope can restore replicative capacity, the kinetics with which they arise remains unknown. Additionally, certain patterns of linked mutations associated with CD8+T cell epitope escape in these highly conserved regions may lead to variable levels of viral fitness. Here, we used pyrosequencing to investigate the kinetics and patterns of mutations surrounding the Mamu-A1*00101-bound Gag181-189CM9 CD8+T cell epitope. We obtained more than 400 reads for each sequencing time point, allowing us to confidently detect the emergence of viral variants bearing escape mutations with frequencies as low as 1% of the circulating virus. With this level of detail, we demonstrate that compensatory mutations generally arise concomitantly with Gag181-189CM9 escape mutations. We observed distinct patterns of linked flanking mutations, most of which were found downstream of Gag181-189CM9. Our data indicate that, whereas Gag181-189CM9 escape is much more complex that previously appreciated, it occurs in a coordinated fashion, with very specific patterns of flanking mutations required for immune evasion. This is the first detailed report of the ontogeny of compensatory mutations that allow CD8+T cell epitope escape in infected individuals.