bluuebunny/crossref_metadata_2025 huggingface dataset:
Sample-based engine noise synthesis using an enhanced pitch-synchronous overlap-and-add method
Authors: Jagla Jan , Maillard Julien , Martin Nadine
Published: November 2012

An algorithm for the real time synthesis of internal combustion engine noise is presented. Through the analysis of a recorded engine noise signal of continuously varying engine speed, a dataset of sound samples is extracted allowing the real time synthesis of the noise induced by arbitrary evolutions of engine speed. The sound samples are extracted from a recording spanning the entire engine speed range. Each sample is delimitated such as to contain the sound emitted during one cycle of the engine plus the necessary overlap to ensure smooth transitions during the synthesis. The proposed approach, an extension of the PSOLA method introduced for speech processing, takes advantage of the specific periodicity of engine noise signals to locate the extraction instants of the sound samples. During the synthesis stage, the sound samples corresponding to the target engine speed evolution are concatenated with an overlap and add algorithm. It is shown that this method produces high quality audio restitution with a low computational load. It is therefore well suited for real time applications.
Improved perception of speech in noise and Mandarin tones with acoustic simulations of harmonic coding for cochlear implants
Authors: Li Xing , Nie Kaibao , Imennov Nikita S. , Won Jong Ho , Drennan Ward R. , Rubinstein Jay T. , Atlas Les E.
Published: November 2012

Harmonic and temporal fine structure (TFS) information are important cues for speech perception in noise and music perception. However, due to the inherently coarse spectral and temporal resolution in electric hearing, the question of how to deliver harmonic and TFS information to cochlear implant (CI) users remains unresolved. A harmonic-single-sideband-encoder [(HSSE); Nie et al. (2008). Proceedings of IEEE International Conference on Acoustics, Speech, and Signal Processing; Lie et al., (2010). Proceedings of IEEE International Conference on Acoustics, Speech, and Signal Processing] strategy has been proposed that explicitly tracks the harmonics in speech and transforms them into modulators conveying both amplitude modulation and fundamental frequency information. For unvoiced speech, HSSE transforms the TFS into a slowly varying yet still noise-like signal. To investigate its potential, four- and eight-channel vocoder simulations of HSSE and the continuous-interleaved-sampling (CIS) strategy were implemented, respectively. Using these vocoders, five normal-hearing subjects’ speech recognition performance was evaluated under different masking conditions; another five normal-hearing subjects’ Mandarin tone identification performance was also evaluated. Additionally, the neural discharge patterns evoked by HSSE- and CIS-encoded Mandarin tone stimuli were simulated using an auditory nerve model. All subjects scored significantly higher with HSSE than with CIS vocoders. The modeling analysis demonstrated that HSSE can convey temporal pitch cues better than CIS. Overall, the results suggest that HSSE is a promising strategy to enhance speech perception with CIs.
Narrow sidebranch arrays for low frequency duct noise control
Authors: Tang S. K.
Published: November 2012

The present study investigates the sound transmission loss across a section of an infinitely long duct where one or more narrow sidebranch tubes are installed flushed with the duct wall. The finite-element method is used to compute the wave propagation characteristics, and a simplified theoretical analysis is carried out at the same time to explain the wave mechanism at frequencies of high sound reduction. Results show that the high sound transmission loss at a particular frequency is due to the concerted actions of three consecutive sidebranch tubes with the most upstream one in the resonant state. The expansion chamber effect of the setup also plays a role in enhancing sound attenuation at non-resonance frequencies. Broadband performance of the device can be greatly enhanced by appropriate arrangements of tube lengths and/or by coupling arrays on the two sides of the duct.
Particle filtering for arrival time tracking in space and source localization
Authors: Michalopoulou Zoi-Heleni , Jain Rashi
Published: November 2012

Locating and tracking a source in an ocean environment and estimating environmental parameters of a sound propagation medium are critical tasks in ocean acoustics. Many approaches for both are based on full field calculations which are computationally intensive and sensitive to assumptions on the structure of the environment. Alternative methods that use only select features of the acoustic field for localization and environmental parameter estimation have been proposed. The focus of this paper is the development of a method that extracts arrival times and amplitudes of distinct paths from measured acoustic time-series using sequential Bayesian filtering, namely, particle filtering. These quantities, along with complete posterior probability density functions, also extracted by filtering, are employed in source localization and bathymetry estimation. Aspects of the filtering methodology are presented and studied in terms of their impact on the uncertainty in the arrival time estimates. Using the posterior probability densities of arrival times, source localization and water depth estimation are performed for the Haro Strait Primer experiment; the results are compared to those of conventional methods. The comparison demonstrates a significant advantage in the proposed approach.
Prevalence of absolute pitch: A comparison between Japanese and Polish music students
Authors: Miyazaki Ken'ichi , Makomaska Sylwia , Rakowski Andrzej
Published: November 2012

Comparable large-scale surveys including an on-site pitch-naming test were conducted with music students in Japan and Poland to obtain more convincing estimates of the prevalence of absolute pitch (AP) and examine how musical experience relates to AP. Participants with accurate AP (95% correct identification) accounted for 30% of the Japanese music students, but only 7% of the Polish music students. This difference in the performance of pitch naming was related to the difference in musical experience. Participants with AP had begun music training at an earlier age (6 years or earlier), and the average year of commencement of musical training was more than 2 years earlier for the Japanese music students than for the Polish students. The percentage of participants who had received early piano lessons was 94% for the Japanese musically trained students but was 72% for the Polish music students. Approximately one-third of the Japanese musically trained students had attended the Yamaha Music School, where lessons on piano or electric organ were given to preschool children in parallel with fixed-do solfège singing training. Such early music instruction was not as common in Poland. The relationship of AP with early music training is discussed.
Bistatic, above-critical angle scattering measurements of fully buried unexploded ordnance (UXO) and clutter
Authors: Waters Z. J. , Simpson H. J. , Sarkissian A. , Dey S. , Houston B. H. , Bucaro J. A. , Yoder T. J.
Published: November 2012

Laboratory grade bistatic scattering measurements are conducted in order to examine the acoustic response of realistic fully buried unexploded ordnance (UXO) from above-critical angle insonification, between 2 and 40 kHz. A 127 mm diameter rocket UXO, a 155 mm diameter artillery shell, a natural rock of approximately the same size, and a cinder block are fully buried in water-saturated medium grained sand (mean grain diameter, 240 μm) at depths of 10 cm below the water–sediment interface. A two-dimensional array of bistatic scattering measurements is generated synthetically by scanning a single hydrophone in steps of 3 cm over a 1 m × 1 m patch directly above the targets at a height of 20 cm above the water–sediment interface. Three-dimensional volumetric acoustic images generated from the return waveforms reveal scattering components attributed to geometric and elastic scattering, as well as multiple-scattering interactions of returns between the sediment–water interface and the buried objects. The far-field target strength of the objects is estimated through extrapolation of the angular spectrum. Agreement is found between experimental data and simulated data generated from a finite-element-based, three-dimensional time-harmonic model (2–25 kHz). Separation of the measured UXO from the clutter objects is demonstrated through exploitation of structural-acoustics-based features.
Temporary threshold shifts and recovery in a harbor porpoise (Phocoena phocoena) after octave-band noise at 4 kHz
Authors: Kastelein Ronald A. , Gransier Robin , Hoek Lean , Olthuis Juul
Published: November 2012

Safety criteria for underwater sound produced during offshore pile driving are needed to protect marine mammals. A harbor porpoise was exposed to fatiguing noise at 18 sound pressure level (SPL) and duration combinations. Its temporary hearing threshold shift (TTS) and hearing recovery were quantified with a psychoacoustic technique. Octave-band white noise centered at 4 kHz was the fatiguing stimulus at three mean received SPLs (124, 136, and 148 dB re 1 μPa) and at six durations (7.5, 15, 30, 60, 120, and 240 min). Approximate received sound exposure levels (SELs) varied between 151 and 190 dB re 1 μPa2 s. Hearing thresholds were determined for a narrow-band frequency-swept sine wave (3.9–4.1 kHz; 1 s) before exposure to the fatiguing noise, and at 1–4, 4–8, 8–12, 48, and 96 min after exposure. The lowest SEL (151 dB re 1 μPa2 s) which caused a significant TTS1–4 was due to exposure to an SPL of 124 dB re 1 μPa for 7.5 min. The maximum TTS1–4, induced after a 240 min exposure to 148 dB re 1 μPa, was around 15 dB at a SEL of 190 dB re 1 μPa2 s. Recovery time following TTS varied between 4 min and under 96 min, depending on the exposure level, duration, and the TTS induced.
Annoyance and self-reported sleep disturbance due to night-time railway noise examined in the field
Authors: Pennig Sibylle , Quehl Julia , Mueller Uwe , Rolny Vinzent , Maass Hartmut , Basner Mathias , Elmenhorst Eva-Maria
Published: November 2012

Railway noise interferes with daytime activities and disturbs sleep leading to annoyance of exposed residents. The main objective of this paper was to establish exposure-response relationships between nocturnal railway noise exposure and annoyance and to examine self-reported sleep disturbances as short-term reactions to noise. In a field study 33 residents living close to railway tracks in the Cologne/Bonn area (Germany) were investigated. Railway noise was measured indoors during nine consecutive nights at each site. Questionnaires referring to annoyance and non-acoustical factors were performed. Annoyance ratings increased significantly with the total number of trains and freight trains per night, and non-significantly with rising number of passenger trains and energy equivalent sound pressure level (LAeq), when adjusting the model for non-acoustical variables. The total number of trains and the number of freight trains also significantly affected self-reported awakening frequency, but no other aspects of subjective sleep disturbances. The responses of this subject sample referring to railway noise in the previous night point to rather low impairments of exposed residents.
Discrete vortex model of a Helmholtz resonator subjected to high-intensity sound and grazing flow
Authors: Dai Xiwen , Jing Xiaodong , Sun Xiaofeng
Published: November 2012

In this paper, a theoretical model is developed to study the acoustical response of a Helmholtz resonator as a duct-branched acoustic absorber subjected to both high-intensity sound and grazing flow. The present model is comprised of a discrete vortex model in combination with a one-dimensional duct sound propagation model. The present work is to study the overall effect of incident sound interacting with grazing flow but putting emphasis on the nonlinear or intermediate regime where the sound intensity has a marked or non-negligible influence on the acoustic behavior of the Helmholtz resonator. The numerical results reveal that the flow field around the orifice is dominated by the evolution of the vortex sheet and the flow pattern is influenced by the ratio of the orifice flow velocity to the grazing flow velocity. When the incident sound pressure is high or the resonance occurs, the resonator shows nonlinearity, i.e., the acoustic impedance and absorption coefficient vary not only with duct flow Mach number buy also with incident frequency and incident sound pressure level.
Humpback whale (Megaptera novaeangliae) singers in Hawaii are attracted to playback of similar song (L)
Authors: Darling James D. , Jones Meagan E. , Nicklin Charles P.
Published: November 2012

The use of playback experiments to study humpback whale song was assessed. Singers clearly detected playback song while singing and with other singers in the distance. Singers approached or joined song similar to their own from as far as 800 m but did not do so for a different (foreign) song. In one compound trial, on the playback of different song, the singer moved away and continued singing; when the playback was changed to similar song, it stopped singing and joined the playback speaker. Song playback experiments on the breeding grounds are viable and may provide insight into song function.
Bayesian three-dimensional reconstruction of toothed whale trajectories: Passive acoustics assisted with visual and tagging measurements
Authors: Laplanche Christophe
Published: November 2012

The author describes and evaluates a Bayesian method to reconstruct three-dimensional toothed whale trajectories from a series of echolocation signals. Localization by using passive acoustic data (time of arrival of source signals at receptors) is assisted by using visual data (coordinates of the whale when diving and resurfacing) and tag information (movement statistics). The efficiency of the Bayesian method is compared to the standard minimum mean squared error statistical approach by comparing the reconstruction results of 48 simulated sperm whale (Physeter macrocephalus) trajectories. The use of the advanced Bayesian method reduces bias (standard deviation) with respect to the standard method up to a factor of 8.9 (13.6). The author provides open-source software which is functional with acoustic data which would be collected in the field from any three-dimensional receptor array design. This approach renews passive acoustics as a valuable tool to study the underwater behavior of toothed whales.
Standards Meetings Calendar–National
Authors: Blaeser Susan B. , Schomer Paul D.
Published: November 2012

American National Standards (ANSI Standards) developed by Accredited Standards Committees S1, S2, S3, and S12 in the areas of acoustics, mechanical vibration and shock, bioacoustics, and noise, respectively, are published by the Acoustical Society of America (ASA). In addition to these standards, ASA publishes catalogs of Acoustical Standards, both National and International. To receive copies of the latest Standards catalogs, please contact Susan B. Blaeser.

Comments are welcomed on all material in Acoustical Standards News.

This Acoustical Standards News section in JASA, as well as the National and International Catalogs of Acoustical Standards, and other information on the Standards Program of the Acoustical Society of America, are available via the ASA home page: http://acousticalsociety.org.
An immersed boundary computational model for acoustic scattering problems with complex geometries
Authors: Sun Xiaofeng , Jiang Yongsong , Liang An , Jing Xiaodong
Published: November 2012

An immersed boundary computational model is presented in order to deal with the acoustic scattering problem by complex geometries, in which the wall boundary condition is treated as a direct body force determined by satisfying the non-penetrating boundary condition. Two distinct discretized grids are used to discrete the fluid domain and immersed boundary, respectively. The immersed boundaries are represented by Lagrangian points and the direct body force determined on these points is applied on the neighboring Eulerian points. The coupling between the Lagrangian points and Euler points is linked by a discrete delta function. The linearized Euler equations are spatially discretized with a fourth-order dispersion-relation-preserving scheme and temporal integrated with a low-dissipation and low-dispersion Runge-Kutta scheme. A perfectly matched layer technique is applied to absorb out-going waves and in-going waves in the immersed bodies. Several benchmark problems for computational aeroacoustic solvers are performed to validate the present method.
Release from masking of low-frequency complex tones by high-frequency complex tone cue bands
Authors: Josupeit Angela , Hohmann Volker , van de Par Steven
Published: November 2012

This study investigated the influence of high-frequency cue bands on the detection and discrimination of low-frequency target bands presented in a 3000-Hz low-pass noise masker. Target and cue bands were complex tones with 80-Hz spacing. The cue band consisted of 60 components starting at 4000 Hz; targets consisted of four components starting at different frequencies (500, 700, 1000, 1200, and 1500 Hz). Targets were presented with different durations within the 500-ms masker; target and cue bands had a common on- and offset. Presentation of the high-frequency complex tone significantly enhanced both the discrimination and detection thresholds by 2–3 dB.
Development and Disintegration of Maya Political Systems in Response to Climate Change
Authors: Kennett Douglas J. , Breitenbach Sebastian F. M. , Aquino Valorie V. , Asmerom Yemane , Awe Jaime , Baldini James U.L. , Bartlein Patrick , Culleton Brendan J. , Ebert Claire , Jazwa Christopher , Macri Martha J. , Marwan Norbert , Polyak Victor , Prufer Keith M. , Ridley Harriet E. , Sodemann Harald , Winterhalder Bruce , Haug Gerald H.
Published: November 2012

Maya and Climate

Climate has affected the vitality of many different societies in the past, as shown by numerous records across the globe and throughout human history. One of the most obvious and spectacular examples of this is from the Classic Maya civilization, whose advanced culture left highly detailed records of all aspects of their existence between 300 and 1000 C.E.

Kennett
et al.

(p.
788
; see the cover) present a detailed climate record derived from a stalagmite collected from a cave in Belize, in the midst of the Classic Maya settlement. The fine resolution and precise dating of the record allows changes in precipitation to be related to the politics, war, and population fluctuations of the Mayans.
Optical Control of Protein Activity by Fluorescent Protein Domains
Authors: Zhou Xin X. , Chung Hokyung K. , Lam Amy J. , Lin Michael Z.
Published: November 2012

Optogenetic Control

Fluorescent proteins are widely used as optical sensors; however, optical control of protein activity remains challenging.

Zhou
et al.

(p.
810
) describe an approach that allows both sensing and control. Domains of the fluorescent protein Dronpa were designed to dimerize with one another and were fused to each of the termini of an enzyme domain. In the dark, the domains dimerized and inhibited the enzyme. However, exposure to light induced Dronpa dissociation and activated the enzyme, allowing optogenetic control.
Epigenetic Islands in a Genetic Ocean
Authors: Schübeler Dirk
Published: November 2012

Mammalian methylomes reveal how DNA methylation is influenced by the underlying nucleotide sequence.
A Less Cloudy Future: The Role of Subtropical Subsidence in Climate Sensitivity
Authors: Fasullo John T. , Trenberth Kevin E.
Published: November 2012

Sensitivity Training

Equilibrium climate sensitivity—the increase in global mean surface air temperature caused by the doubling of the concentration of atmospheric CO
2
—is needed to predict anthropogenic climate change. For decades, models have estimated its value to be between 1.5° and 4.5°C, but with too high an uncertainty to have strong predictive value.
Fasullo and Trenberth
(p.
792
; see the Perspective by

Shell

) show that the seasonal variation of tropospheric relative humidity is related to climate sensitivity and could be used to constrain models and narrow the range of equilibrium climate sensitivity estimates, thereby allowing more accurate predictions of future warming.
Driving a Macroscopic Oscillator with the Stochastic Motion of a Hydrogen Molecule
Authors: Lotze Christian , Corso Martina , Franke Katharina J. , von Oppen Felix , Pascual Jose Ignacio
Published: November 2012

Putting Noise to Work

Extracting energy from a noisy system (one that moves randomly) is possible if a mechanical system can induce periodicity on its motion, a phenomenon called stochastic resonance.

Lotze
et al.

(p.
779
; see the Perspective by

Bockrath

) created stochastic resonances between the cantilever attached to a scanning tunneling microscope tip and a hydrogen molecule adsorbed on a copper surface at cryogenic temperatures. The tunneling electrons at a particular bias voltage could excite the hydrogen molecules and couple their random motion to that of the cantilever, driving periodic oscillations.
A Decorated Virus Cannot Hide
Authors: Herzog Roland W. , Ostrov David A.
Published: November 2012

A protein that promotes blood coagulation also enables the immune system to recognize a viral pathogen.
Constraining Cloud Feedbacks
Authors: Shell Karen M.
Published: November 2012

A simple diagnostic circumvents the need for measuring cloud properties, helping to improve climate sensitivity estimates.
Speak Up for Science Funding
Authors: Leshner Alan I. , Woolley Mary
Published: November 2012

The U.S. elections are over, and sitting policy-makers must turn their attention urgently to the “fiscal cliff,” a perfect storm of budget landmines laid by Congress and two administrations that threaten to go into effect in early January. Congress and the president must rapidly make hugely important decisions about the debt limit, the expiration of Bush-era tax cuts, and possible draconian across-the-board budget cuts in defense and nondefense accounts known as “sequestration.” Business leaders and other interests are rallying to force action, alarmed that cuts will be directed at them. Those not heard from will probably have the most to lose. It is simply not enough that scientific societies and advocacy organizations speak up. It is essential that every member of the science and engineering community personally convey to policy-makers and the U.S. public the great importance of strong science funding to the future of the country.
Scientists Assess Damage From Sandy's Deadly Punch
Authors: Malakoff David
Published: November 2012

Hurricane Sandy presented unprecedented opportunities to measure beaches and shorelines along its expected path for data that would improve computer models that predict coastal flooding and erosion.
Poor but Smart
Authors: Kupferschmidt Kai
Published: November 2012

It may not be an economic success. But the new, reunited Berlin has become one of Europe's hottest cities for science.
Genetic Analysis of Non-Hydrogen Sulfide-Producing Salmonella enterica Serovar Typhimurium and S. enterica Serovar Infantis Isolates in Japan
Authors: Sakano Chieko , Kuroda Makoto , Sekizuka Tsuyoshi , Ishioka Taisei , Morita Yukio , Ryo Akihide , Tsukagoshi Hiroyuki , Kawai Yuko , Inoue Nobuko , Takada Hayato , Ogaswara Yumiko , Nishina Atsuyoshi , Shimoda Masa-aki , Kozawa Kunihisa , Oishi Kazunori , Kimura Hirokazu
Published: November 2012

Whole-genome sequencing of non-H
2
S-producing
Salmonella enterica
serovar Typhimurium and
S. enterica
serovar Infantis isolates from poultry meat revealed a nonsense mutation in the
phsA
thiosulfate reductase gene and carriage of a CMY-2 β-lactamase. The lack of production of H
2
S might lead to the incorrect identification of
S. enterica
isolates carrying antimicrobial resistance genes.
Genetic Diversity of Burkholderia contaminans Isolates from Cystic Fibrosis Patients in Argentina
Authors: Martina Pablo , Bettiol Marisa , Vescina Cecilia , Montanaro Patricia , Mannino M. Constanza , Prieto Claudia I. , Vay Carlos , Naumann Dieter , Schmitt Juergen , Yantorno Osvaldo , Lagares Antonio , Bosch Alejandra
Published: November 2012

A total of 120
Burkholderia cepacia
complex isolates collected during 2004–2010 from 66 patients in two cystic fibrosis reference centers in Argentina were analyzed.
Burkholderia contaminan
s was the species most frequently recovered (57.6%), followed by
Burkholderia cenocepacia
(15%), a species distribution not reported so far. The
recA
-PCR-based techniques applied to the
B. contaminans
isolates revealed that 85% of the population carried the
recA
-ST-71 allele. Our results showed the utility of BOX-PCR genotyping in analyzing
B. contaminans
diversity. This approach allowed us to address clonal transmission during an outbreak and the genetic changes occurring in infecting bacteria over the course of chronic infection.
Characterization of a Tsukamurella Pseudo-Outbreak by Phenotypic Tests, 16S rRNA Sequencing, Pulsed-Field Gel Electrophoresis, and Metabolic Footprinting
Authors: To Kelvin K. W. , Fung Ami M. Y. , Teng Jade L. L. , Curreem Shirly O. T. , Lee Kim-Chung , Yuen Kwok-Yung , Lam Ching-Wan , Lau Susanna K. P. , Woo Patrick C. Y.
Published: November 2012

We report a pseudo-outbreak of
Tsukamurella
due to improperly wrapped scissors used for processing of tissue specimens. A polyphasic approach, involving biochemical, genetic, and metabolomic techniques, was used in the laboratory investigation. This report highlights that early recognition of pseudo-outbreaks is important in preventing unnecessary and incorrect treatment of patients.
Colonization Dynamics of Antibiotic-Resistant Coagulase-Negative Staphylococci in Neonates
Authors: Hira Vishal , Kornelisse René F. , Sluijter Marcel , Kamerbeek Alike , Goessens Wil H. F. , de Groot Ronald , Hermans Peter W. M.
Published: November 2012

Coagulase-negative staphylococci (CoNS) isolated in neonatal late-onset sepsis are often antibiotic resistant. We analyzed CoNS from skin and feces of neonates during hospitalization. Antibiotic resistance of skin isolates increased during hospitalization, especially in
Staphylococcus haemolyticus
.
Staphylococcus warneri
showed low antibiotic resistance. Our data suggest that different CoNS species may play distinct roles in colonization.
Highly Attenuated Recombinant Vesicular Stomatitis Virus VSV-12′GFP Displays Immunogenic and Oncolytic Activity
Authors: van den Pol Anthony N. , Davis John N.
Published: November 2012

Vesicular stomatitis virus (VSV) has shown considerable promise both as an immunization vector and as an oncolytic virus. In both applications, an important concern is the safety profile of the virus. To generate a highly attenuated virus, we added two reporter genes to the 3′ end of the VSV genome, thereby shifting the NPMGL genes from positions 1 to 5 to positions 3 to 7. The resulting virus (VSV-12′GFP) was highly attenuated, generating smaller plaques than four other attenuated VSVs. In one-step growth curves, VSV-12′GFP displayed the slowest growth kinetics. The mechanism of attenuation appears to be due to reduced expression of VSV genes downstream of the reporter genes, as suggested by a 10.4-fold reduction in L-protein RNA transcript. Although attenuated, VSV-12′GFP was highly effective at generating an immune response, indicated by a high-titer antibody response against the green fluorescent protein (GFP) expressed by the virus. Although VSV-12′GFP was more attenuated than other VSVs on both normal and cancer cells, it nonetheless showed a greater level of infection of human cancer cells (glioma and melanoma) than of normal cells, and this effect was magnified in glioma by interferon application, indicating selective oncolysis. Intravenous VSV-12′GFP selectively infected human gliomas implanted into SCID mice subcutaneously or intracranially. All postnatal day 16 mice given intranasal VSV-12′GFP survived, whereas only 10% of those given VSV-G/GFP survived, indicating reduced neurotoxicity. Intratumoral injection of tumors with VSV-12′GFP dramatically suppressed tumor growth and enhanced survival. Together these data suggest this recombinant virus merits further study for its oncolytic and vaccine potential.
HIV-1 Resistance to Maraviroc Conferred by a CD4 Binding Site Mutation in the Envelope Glycoprotein gp120
Authors: Ratcliff Annette N. , Shi Wuxian , Arts Eric J.
Published: November 2012

Maraviroc (MVC) is a CCR5 antagonist that inhibits HIV-1 entry by binding to the coreceptor and inducing structural alterations in the extracellular loops. In this study, we isolated MVC-resistant variants from an HIV-1 primary isolate that arose after 21 weeks of tissue culture passage in the presence of inhibitor. gp120 sequences from passage control and MVC-resistant cultures were cloned into NL4-3 via yeast-based recombination followed by sequencing and drug susceptibility testing. Using 140 clones, three mutations were linked to MVC resistance, but none appeared in the V3 loop as was the case with previous HIV-1 strains resistant to CCR5 antagonists. Rather, resistance was dependent upon a single mutation in the C4 region of gp120. Chimeric clones bearing this N425K mutation replicated at high MVC concentrations and displayed significant shifts in 50% inhibitory concentrations (IC
50
s), characteristic of resistance to all other antiretroviral drugs but not typical of MVC resistance. Previous reports on MVC resistance describe an ability to use a drug-bound form of the receptor, leading to reduction in maximal drug inhibition. In contrast, our structural models on K425 gp120 suggest that this resistant mutation impacts CD4 interactions and highlights a novel pathway for MVC resistance.
Engagement of the ATR-Dependent DNA Damage Response at the Human Papillomavirus 18 Replication Centers during the Initial Amplification
Authors: Reinson Tormi , Toots Mart , Kadaja Meelis , Pipitch Regina , Allik Mihkel , Ustav Ene , Ustav Mart
Published: November 2012

We have previously demonstrated that the human papillomavirus (HPV) genome replicates effectively in U2OS cells after transfection using electroporation. The transient extrachromosomal replication, stable maintenance, and late amplification of the viral genome could be studied for high- and low-risk mucosal and cutaneous papillomaviruses. Recent findings indicate that the cellular DNA damage response (DDR) is activated during the HPV life cycle and that the viral replication protein E1 might play a role in this process. We used a U2OS cell-based system to study E1-dependent DDR activation and the involvement of these pathways in viral transient replication. We demonstrated that the E1 protein could cause double-strand DNA breaks in the host genome by directly interacting with DNA. This activity leads to the induction of an ATM-dependent signaling cascade and cell cycle arrest in the S and G
2
phases. However, the transient replication of HPV genomes in U2OS cells induces the ATR-dependent pathway, as shown by the accumulation of γH2AX, ATR-interacting protein (ATRIP), and topoisomerase IIβ-binding protein 1 (TopBP1) in viral replication centers. Viral oncogenes do not play a role in this activation, which is induced only through DNA replication or by replication proteins E1 and E2. The ATR pathway in viral replication centers is likely activated through DNA replication stress and might play an important role in engaging cellular DNA repair/recombination machinery for effective replication of the viral genome upon active amplification.
Gangliosides Have a Functional Role during Rotavirus Cell Entry
Authors: Martínez Miguel Angel , López Susana , Arias Carlos F. , Isa Pavel
Published: November 2012

Cell entry of rotaviruses is a complex process, which involves sequential interactions with several cell surface molecules. Among the molecules implicated are gangliosides, glycosphingolipids with one or more sialic acid (SA) residues. The role of gangliosides in rotavirus cell entry was studied by silencing the expression of two key enzymes involved in their biosynthesis—the UDP-glucose:ceramide glucosyltransferase (UGCG), which transfers a glucose molecule to ceramide to produce glucosylceramide GlcCer, and the lactosyl ceramide-α-2,3–sialyl transferase 5 (GM3-s), which adds the first SA to lactoceramide-producing ganglioside GM3. Silencing the expression of both enzymes resulted in decreased ganglioside levels (as judged by GM1a detection). Four rotavirus strains tested (human Wa, simian RRV, porcine TFR-41, and bovine UK) showed a decreased infectivity in cells with impaired ganglioside synthesis; however, their replication after bypassing the entry step was not affected, confirming the importance of gangliosides for cell entry of the viruses. Interestingly, viral binding to the cell surface was not affected in cells with inhibited ganglioside synthesis, but the infectivity of all strains tested was inhibited by preincubation of gangliosides with virus prior to infection. These data suggest that rotaviruses can attach to cell surface in the absence of gangliosides but require them for productive cell entry, confirming their functional role during rotavirus cell entry.
Humoral Immunity to Smallpox Vaccines and Monkeypox Virus Challenge: Proteomic Assessment and Clinical Correlations
Authors: Townsend M. B. , Keckler M. S. , Patel N. , Davies D. H. , Felgner P. , Damon I. K. , Karem K. L.
Published: November 2012

Despite the eradication of smallpox, orthopoxviruses (OPV) remain public health concerns. Efforts to develop new therapeutics and vaccines for smallpox continue through their evaluation in animal models despite limited understanding of the specific correlates of protective immunity. Recent monkeypox virus challenge studies have established the black-tailed prairie dog (
Cynomys ludovicianus
) as a model of human systemic OPV infections. In this study, we assess the induction of humoral immunity in humans and prairie dogs receiving Dryvax, Acam2000, or Imvamune vaccine and characterize the proteomic profile of immune recognition using enzyme-linked immunosorbent assays (ELISA), neutralization assays, and protein microarrays. We confirm anticipated similarities of antigenic protein targets of smallpox vaccine-induced responses in humans and prairie dogs and identify several differences. Subsequent monkeypox virus intranasal infection of vaccinated prairie dogs resulted in a significant boost in humoral immunity characterized by a shift in reactivity of increased intensity to a broader range of OPV proteins. This work provides evidence of similarities between the vaccine responses in prairie dogs and humans that enhance the value of the prairie dog model system as an OPV vaccination model and offers novel findings that form a framework for examining the humoral immune response induced by systemic orthopoxvirus infection.
Expression of Prototype Foamy Virus Pol as a Gag-Pol Fusion Protein Does Not Change the Timing of Reverse Transcription
Authors: Jackson Dana L. , Lee Eun-Gyung , Linial Maxine L.
Published: November 2012

Foamy viruses are retroviruses whose Pol protein is synthesized without Gag from a spliced mRNA. Unlike orthoretroviruses, reverse transcription occurs during viral assembly, leading to DNA-containing virions. When prototype foamy virus Pol is expressed as an orthoretroviral-like Gag-Pol fusion protein, reverse transcription also occurs late in viral replication, as measured by the timing of reverse transcriptase sensitivity to the inhibitor 3′-azido-3′deoxythymidine (AZT). Thus, timing of reverse transcription is intrinsic to Pol itself.
Mucosal Tissue Tropism and Dissemination of HIV-1 Subtype B Acute Envelope-Expressing Chimeric Virus
Authors: King Deborah F. L. , Siddiqui Asna A. , Buffa Viviana , Fischetti Lucia , Gao Yong , Stieh Daniel , McKay Paul F. , Rogers Paul , Ochsenbauer Christina , Kappes John C. , Arts Eric J. , Shattock Robin J.
Published: November 2012

Human immunodeficiency virus type 1 (HIV-1) transmission results from infection with one or a small number of variants from the donor quasispecies. Transmitted/founder (T/F) viruses have recently been identified from acutely infected patients, but the way in which they interact with primary targets of HIV-1 infection is poorly understood. We have conducted a biological characterization of a panel of subtype B T/F acute and chronic envelope (Env)-expressing chimeric virus in primary human target cells and mucosal tissues. Both acute and chronic Envs preferentially replicated in peripheral blood mononuclear cells (PBMC) and a CD4 T-cell line compared to monocyte-derived macrophages, or dendritic cells (DC). In a model of
trans
infection from monocyte-derived dendritic cells to T cells, chimeric virus from acute Envs achieved significantly lower titers compared to chronic Envs. Challenge of primary human mucosal tissues revealed significantly higher levels of replication in chronic Env-expressing virus in rectal tissue compared to cervical and penile tissues and enhanced replication in tonsillar tissue relative to acute Envs. In agreement with data from the DC to T-cell
trans
infection assay, chronic Env-chimeric virus pools were transmitted more efficiently by migratory cells from cervical and penile tissues to CD4
+
T cells than individual acute Env chimeras. These data indicate that virus with HIV-1 Envs of transmitted acute infections preferentially replicate in T cells rather than macrophages or dendritic cells and are less efficiently transmitted from antigen-presenting cells to CD4 T cells than chronic Envs. Such properties together with chemokine (C-C motif) receptor 5 (CCR5) use may confer an advantage for transmission.
Host mTORC1 Signaling Regulates Andes Virus Replication
Authors: McNulty Shannon , Flint Mike , Nichol Stuart T. , Spiropoulou Christina F.
Published: November 2012

Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease characterized by pulmonary edema, with fatality rates of 35 to 45%. Disease occurs following infection with pathogenic New World hantaviruses, such as Andes virus (ANDV), which targets lung microvascular endothelial cells. During replication, the virus scavenges 5′-m
7
G caps from cellular mRNA to ensure efficient translation of viral proteins by the host cell cap-dependent translation machinery. In cells, the mammalian target of rapamycin (mTOR) regulates the activity of host cap-dependent translation by integrating amino acid, energy, and oxygen availability signals. Since there is no approved pharmacological treatment for HPS, we investigated whether inhibitors of the mTOR pathway could reduce hantavirus infection. Here, we demonstrate that treatment with the FDA-approved rapamycin analogue temsirolimus (CCI-779) blocks ANDV protein expression and virion release but not entry into primary human microvascular endothelial cells. This effect was specific to viral proteins, as temsirolimus treatment did not block host protein synthesis. We confirmed that temsirolimus targeted host mTOR complex 1 (mTORC1) and not a viral protein, as knockdown of mTORC1 and mTORC1 activators but not mTOR complex 2 components reduced ANDV replication. Additionally, primary fibroblasts from a patient with tuberous sclerosis exhibited increased mTORC1 activity and increased ANDV protein expression, which were blocked following temsirolimus treatment. Finally, we show that ANDV glycoprotein Gn colocalized with mTOR and lysosomes in infected cells. Together, these data demonstrate that mTORC1 signaling regulates ANDV replication and suggest that the hantavirus Gn protein may modulate mTOR and lysosomal signaling during infection, thus bypassing the cellular regulation of translation.
Biogenesis of the Vaccinia Virus Membrane: Genetic and Ultrastructural Analysis of the Contributions of the A14 and A17 Proteins
Authors: Unger Bethany , Mercer Jason , Boyle Kathleen A. , Traktman Paula
Published: November 2012

Vaccinia virus membrane biogenesis requires the A14 and A17 proteins. We show here that both proteins can associate with membranes co- but not posttranslationally, and we perform a structure function analysis of A14 and A17 using inducible recombinants. In the absence of A14, electron-dense virosomes and distinct clusters of small vesicles accumulate; in the absence of A17, small vesicles form a corona around the virosomes. When the proteins are induced at 12 h postinfection (hpi), crescents appear at the periphery of the electron-dense virosomes, with the accumulated vesicles likely contributing to their formation. A variety of mutant alleles of A14 and A17 were tested for their ability to support virion assembly. For A14, biologically important motifs within the N-terminal or central loop region affected crescent maturation and the immature virion (IV)→mature virion (MV) transition. For A17, truncation or mutation of the N terminus of A17 engendered a phenotype consistent with the N terminus of A17 recruiting the D13 scaffold protein to nascent membranes. When N-terminal processing was abrogated, virions attempted to undergo the IV-to-MV transition without removing the D13 scaffold and were therefore noninfectious and structurally aberrant. Finally, we show that A17 is phosphorylated exclusively within the C-terminal tail and that this region is a direct substrate of the viral F10 kinase.
In vivo
, the biological competency of A17 was reduced by mutations that prevented its serine-threonine phosphorylation and restored by phosphomimetic substitutions. Precleavage of the C terminus or abrogation of its phosphorylation diminished the IV→MV maturation; a block to cleavage spared virion maturation but compromised the yield of infectious virus.
Exercise regulation of intestinal tight junction proteins
Authors: Zuhl Micah , Schneider Suzanne , Lanphere Katherine , Conn Carole , Dokladny Karol , Moseley Pope
Published: November 2012

Gastrointestinal distress, such as diarrhoea, cramping, vomiting, nausea and gastric pain are common among athletes during training and competition. The mechanisms that cause these symptoms are not fully understood. The stress of heat and oxidative damage during exercise causes disruption to intestinal epithelial cell tight junction proteins resulting in increased permeability to luminal endotoxins. The endotoxin moves into the blood stream leading to a systemic immune response. Tight junction integrity is altered by the phosphoylation state of the proteins occludin and claudins, and may be regulated by the type of exercise performed. Prolonged exercise and high-intensity exercise lead to an increase in key phosphorylation enzymes that ultimately cause tight junction dysfunction, but the mechanisms are different. The purpose of this review is to (1) explain the function and physiology of tight junction regulation, (2) discuss the effects of prolonged and high-intensity exercise on tight junction permeability leading to gastrointestinal distress and (3) review agents that may increase or decrease tight junction integrity during exercise.
Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study)
Authors: Mullol Joaquim , Alobid Isam , Mariño-Sánchez Franklin , Quintó Llorenç , de Haro Josep , Bernal-Sprekelsen Manuel , Valero Antonio , Picado Cèsar , Marin Concepció
Published: November 2012

Objectives

To investigate olfaction in general population, prevalence of olfactory dysfunction and related risk factors.

Design

Cross-sectional population-based survey, distributing four microencapsulated odorants (rose, banana, musk and gas) and two self-administered questionnaires (odour description; epidemiology/health status).

Setting

The survey was distributed to general population through a bilingual (Catalan, Spanish) newspaper in Catalonia (Spain), on December 2003.

Participants

Newspaper readers of all ages and gender; 9348 surveys were analysed from the 10 783 returned.

Main outcome measures

Characteristics of surveyed population, olfaction by age and gender, smell self-perception and smell impairment risk factors. Terms normosmia, hyposmia and anosmia were used when participants detected, recognised or identified all four, one to three or none of the odours, respectively.

Results

Survey profile was a 43-year-old woman with medium–high educational level, living in a city. Olfaction was considered normal in 80.6% (detection), 56% (recognition/memory) and 50.7% (identification). Prevalence of smell dysfunction was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48% hyposmia). Olfaction was worse (p<0.0001) in men than in women through all ages. There was a significant age-related smell detection decline however smell recognition and identification increased up to fourth decade and declined after the sixth decade of life. Risk factors for anosmia were: male gender, loss of smell history and poor olfactory self-perception for detection; low educational level, poor self-perception and pregnancy for recognition; and older age, poor self-perception and history of head trauma and loss of smell for identification. Smoking and exposure to noxious substances were mild protective factors for smell recognition.

Conclusions

Sense of smell in women is better than in men suggesting a learning process during life with deterioration in older ages. Poor self-perception, history of smell loss, head trauma and pregnancy are potential risk factors for olfactory disorders.
Time trend in hospitalised chronic lower respiratory diseases among Danish building and construction workers, 1981–2009: a cohort study
Authors: Tüchsen Finn , Hannerz Harald , Mølgaard Ellen Fisher , Brauer Charlotte , Kirkeskov Lilli
Published: November 2012

Objectives

To show trends in age-standardised hospital admission ratios (SHR) for chronic lower respiratory diseases, estimated for Danish construction workers over three time periods (1981–1990, 1991–2000, 2001–2009).

Design

Within consecutive cohorts of all male building and construction workers in Denmark, selected occupations: bricklayers, carpenters, electricians, painters, plumbers and ‘other construction workers’ were followed up for hospitalisation due to chronic lower respiratory diseases. SHR was calculated for each occupation and time period. Time trend was calculated for construction workers at large using Poisson regression.

Setting

Denmark.

Participants

All gainfully employed male building and construction workers aged 20 or more.

Primary and secondary outcome measures

Age-standardised and gender-standardised hospitalisation ratios (SHR).

Results

The number of hospitalised construction workers at large was reduced from 1134 in the first 10-year period to 699 in the last 9-year period. Among all Danish males, it was, however, even more reduced as reflected in the expected number that was down from 1172 to 617. Hence, SHR increased from 97 during 1981–1990, 100 during 1991–2000 to 113 during 2001–2009. It means that SHR increased with an average rate of 0.76% per year (95% CI 0.28 to 1.24) during the study period. A low SHR=72 (95% CI 60 to 87) was found among carpenters in 1981–1990. From 2001 to 2009, high SHRs were found among painters (SHR=147; 95% CI 111 to 192) and plumbers (SHR=132; 95% CI 101 to 171). In general, the selected groups of construction workers had, however, a low or average SHR due to chronic lower respiratory diseases.

Conclusions

The number of hospitalised workers, suffering from chronic lower respiratory diseases, was reduced over time for construction workers, but for all economically active men, it was reduced even more. Therefore, SHR due to chronic lower respiratory diseases increased over time in the construction industry at large.