bluuebunny/crossref_metadata_2025 huggingface dataset:
Solving for the vibro-acoustic interaction between a fluid and a structure with discontinuities by the boundary element method using local/global homogenization
Authors: Danilov Pavel , Bliss Donald
Published: October 2013

The boundary element method (BEM) was used to determine the radiation properties of finite structures with periodically attached impedances. Due to the discontinuities and fine-scale structural wave motion, BEM would generally require small size elements. Local/global homogenization (LGH) was used in order to eliminate the discontinuities and short waves from the problem. LGH provides the global smooth problem, free of discontinuities, but containing all the information needed to describe the radiation. The global problem results in modification of BEM kernels in order to implement coupling with the local part. Instead of the exact solution, BEM used with LGH requires only the smooth global part, allowing fewer elements. Model problems show good accuracy of the method along with a significant reduction of computational costs.
Local/global decomposition for fluid-loaded periodic structures
Authors: Danilov Pavel , Bliss Donald
Published: October 2013

The problem of interaction between a fluid and a structure with periodic impedance attachments is considered. The full solution is divided into two coupled parts: the global part, providing overall structural motion and acoustic radiation, and the local part, containing small structural oscillations and evanescent pressure modes. Fluid loading in the local part results in additional structural inertia, which is conveniently accounted for in the global problem. A separate stand-alone equation is constructed for the global solution. The local part can be recovered afterwards. Specific conditions are imposed on the local and global parts, e.g., the global solution with finite wavenumber support is used to recover the radiating part of the spectrum and the local solution is made to vanish at the impedances. Thus, the global solution describes radiating properties and structural response. Different conditions on the local/global decomposition are considered in order to enhance the accuracy of the method. Application to structures of finite extent is discussed. Model problems showed good accuracy of radiated pressure as well as structural response.
Classroom acoustics and architects: Sightlines and sound
Authors: Williams Terence J.
Published: October 2013

All too often, acoustics in classroom design is a forgotten or ignored subject. Design teams consider structural, mechanical and electrical implications but overlook the fundamental issue of hearing and being heard. As an architect with an interest in architectural acoustics, particularly performance arts venues, we have taken a pragmatic approach, some might say unscientific, to classroom design. A series of case studies is presented that illustrates the challenge of classroom acoustics from an architect’s point of view: not ‘‘what does it look like,’’ but ‘‘how does it sound’’! Because classroom acoustics are so closely aligned to the visual presentation of information, seeing and being seen becomes critical also. Sightlines and sound continue to vie for attention. The challenge is making it work.
Aerodynamic reduction in American English flapping
Authors: Martin Sidney , Romero Joaquin
Published: October 2013

Are all tongue tip gestures for /t,d/ the same? Acoustic and articulatory studies have revealed that /t,d’s show a gradient behavior, in which invariancy is nonexistent. These results undermine phonological rules which represent leniting processes, such as flapping, as a rule where /t,d/ is replaced by an invariant flap. Adding to more evidence for gradiency, an aerodynamic experiment was designed to investigate the nature of alveolar tongue tip gestures, specifically in flapping contexts. Three native speakers of American English were recruited and each yielded 200 tokens, which contained medial /t,d/ in different phonetic contexts (stressed-syllable onset, unstressed-syllable onset, n+/t,d/, l+/t,d/ and r+/t,d/) and in two speaking rates. For each target consonant, duration ratio and airflow rate were obtained. In general, both duration ratio and airflow rate showed gradiency across rate and context. Tokens at a normal speech rate yielded higher ratios and airflow rates than tokens at a faster speech rate. However, rate did not affect each context equally. Accordingly, /t,d’s reveal a gradient behavior which ranges from a canonical stop to complete deletion.
Acoustical propagation modeling using the three-dimensional parabolic equation based code 3DWAPE within a multiprocessing environment
Authors: Castor Kaelig , Sturm Frédéric , Piserchia Pierre Franck
Published: October 2013

In some particular oceanic environments involving bathymetric slopes and horizontal sound speed gradients, the azimuthal coupling can be significant. Fully three-dimensional models are thus needed to account for horizontal refraction. These models need usually high computational resources, especially for broadband calculations and/or for long-range paths where the 3-D effects are clearly accentuated. In this study, numerical simulations using the 3-D parabolic equation model 3DWAPE [F. Sturm, Acust. Acta Acust. 88, 714–717 (2002)] are presented. The calculations are performed on a massively parallel computer providing a high computational efficiency. The message-passing interface (MPI) communication library is used. Two parallelization levels are considered. The first one allows a broadband-signal propagation by distributing independently on different processors the calculations for each frequency. The second one is based on a segmentation of the propagation matrices. Simple methods are used to perform an optimized multiprocessor implementation by equalizing processor workload, and split the number of processors between the two parallelization levels. An analysis of both speedup and efficiency of the algorithm is presented for several configurations. Computational time comparisons are shown for the 3-D ASA benchmark. The algorithm can also be applied to a realistic environment involving sound speed profiles and bathymetry data sets.
Forces generated in biological tissue-like media due to second-order effects in the focal region of an ultrasonic beam
Authors: Ostrovsky Lev , Sutin Alexander , Sarvazyan Armen
Published: October 2013

Several techniques of medical diagnostics have been developed in the last decade based on the application of radiation forces of focused ultrasound. The most commonly considered physical mechanism of the radiation force generation is essentially related to ultrasound beam attenuation. However, in the case of short ultrasonic pulses typical for conventional ultrasonic imaging systems, an additional mechanism of force generation exists that is caused by acoustic nonlinearity of the media and does not explicitly depend on viscous dissipation. For water-like media such as human tissue, our theoretical description of the preceding effects is based on Eckart’s theory of second-order effects in fluids, although modified by taking into account the shear modulus in the rotational component. In our theory, nonlinearity in a pulsed beam produces also a longitudinal component of an averaged force and a resulting displacement. Estimates show that for short acoustic pulses generated in conventional diagnostic ultrasound systems, the latter component can make a significant and even dominant contribution to the averaged displacement in the focal area of an ultrasonic beam.
Using Flanagan’s phase vocoder to improve cochlear implant performance
Authors: Zeng Fan-Gang
Published: October 2013

The cochlear implant has restored partial hearing to more than 100000 deaf people worldwide, allowing the average user to talk on the telephone in quiet environment. However, significant difficulty still remains for speech recognition in noise, music perception, and tonal language understanding. This difficulty may be related to speech processing strategies in current cochlear implants that emphasized the extraction and encoding of the temporal envelope while ignoring the temporal fine structure in speech sounds. A novel strategy was developed based on Flanagan’s phase vocoder [Flanagan and Golden, Bell Syst. Tech. 45, 1493–1509 (1966)], in which frequency modulation was extracted from the temporal fine structure and then added to amplitude modulation in the current cochlear implants. Acoustic simulation results showed that amplitude and frequency modulation contributed complementarily to speech perception with amplitude modulation contributing mainly to intelligibility whereas frequency modulation contributed to speaker identification and auditory grouping. The results also showed that the novel strategy significantly improved cochlear implant performance under realistic listening situations. Overall, the present result demonstrated that Flanagan’s classic work on phase vocoder still shed insight on current problems of both theoretical and practical importance. [Work supported by NIH.]
Source spectra for excised and latex phonatory models
Authors: Alipour Fariborz , Scherer Ronald C.
Published: October 2013

An excised larynx model and a latex physical model were used to study acoustic spectra of the phonatory source as a function of subglottal pressure, glottal adduction, and vocal-fold length. A supraglottal vocal tract was not used, indicating that the acoustic signal corresponded to the output glottal flow. Each model was mounted over an -inch tracheal tube through which flowed pressurized, heated, and humidified air. The subglottal pressure and EGG signal (excised model) were recorded on a personal computer. The mean flow rate, mean subglottal pressure, and SPL were recorded manually, and adduction was specified by the use of interarytenoid shims. The output audio signals from the larynx models were recorded on a DAT recorder. Spectral information of the audio signal was obtained via FFT analysis (Matlab). Preliminary data indicate that the spectral slope did not have a constant dB/octave rate, and spectral slope had a primary dependence on subglottal pressure and a secondary dependence on adduction. Other acoustic details and the differences between the two models will be discussed. [Work supported by NIDCD Grant Number DC03566.]
Time-reversal communication through a highly scattering medium
Authors: Chambers David , Robbins Christopher , Guidry Brian , Elayat Ahmad
Published: October 2013

An ultrasonic time-reversal array system is used to transmit communication signals across an aluminum slab with 195 holes drilled through it. Multiple scattering and mode conversion stretches a 0.4-microsecond transmitted pulse into a received signal that rings for over 75 microseconds with little attenuation. Communication through such a medium is subject to severe multipath distortion. Four variations of a time-reversal receiver are used to mitigate multipath distortion and allow error-free transmission of a variety of bit sequences [see Candy et al. J. Acoust. Soc. Am. Suppl. 115, 2367 (2004)]. Performance of point-to-point receivers constructed from different segments of the Green’s function (channel response) is compared. [This work was performed under the auspices of the U. S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48.]
In vitro comparative study of three devices based on ultrasonic axial transmission
Authors: Muller M. , Talmant M. , Laugier P. , Moilanen P. , Kilappa V. , Timonen J. , Nicholson P. , Cheng S.
Published: October 2013

In the axial transmission technique the velocity of waves propagating in the direction of bone axis is used to characterize cortical bone (radius, tibia, etc.). Corresponding clinically used devices are based on a long wavelength approach (typical frequency around 200 kHz) or shorter wavelength (typical frequency around 1 MHz) compared to bone thickness. They differ also by the methods of wave velocity evaluation. The aim of this study is to compare the sensitivity to bone properties of three representative devices using an in vitro investigation of the same specimens coupled with x-ray determination of bone properties. The moderate correlation between velocities suggests an important impact of site-matching. Among higher frequency devices, the one associated to the bidirectional probe provided generally higher correlation with bone properties than conventional axial transmission. The high-frequency devices are less sensitive to cortical thickness, CSA and trabecular BMD than the low-frequency device because high-frequency waves interrogate a thinner cortical layer than low-frequency waves. Our results suggest that different axial transmission approaches reflect different bone properties. Therefore, a multi-frequency technique might be useful in probing different bone properties at the same time (e.g., cortical thickness and BMD).
Global electro-structural-acoustic filtering in the cochlea
Authors: Ramamoorthy Sripriya , Grosh Karl
Published: October 2013

The active filtering in the cochlea is now believed to be due to the piezo-motility of the Outer Hair Cell (OHC), and the modulation of stereocilia resistance. Physiologically, the OHC resting potential is known to be modulated by the K+ ions in the cochlear fluid entering or leaving the OHC via gated channels, in response to structural motion, which in turn couples the electrical potential in the cochlear fluids to OHCs piezo-motility. However, the electrotonic space-constant of the ionic fluid in the cochlea is not negligible compared to the structural-acoustic wavelength for all frequencies, thus limiting the currently existing models that adopt local structural-electrical interaction. The electrical wave interacts globally with the structural-acoustic wave. This paper proposes a three-dimensional global electro-structural-acoustic linear finite element model to analyze the coupled behavior in the active cochlea. The OHC is modeled as a piezoelectric bar. A cable model is used for the electrical voltages, and a micromechanical model based on Dallos (2002) is proposed. Modeling is maintained as physiological as possible. The active response of the cochlea to acoustic input, Electrically Evoked Oto-Acoustic Emissions, efferent feedback, and the potential of IHC in response to acoustic or electrical input are studied.
A new forecasted method of echo stealth effect for underwater target with laying anechoic tiles
Authors: Zhang Qiong , Zhao Fukuan , Wang Rongqing
Published: October 2013

Its target strength can be reduced undoubtedly for an underwater target that is possessed of laying anechoic tiles. For evaluating its echo stealth effect, traditional ideas are a numerical evaluation and test of the full-scale target. This paper suggests a new forecasted method named ‘‘The Law of Equivalent Proportions:’’ For laying sound-absorbing material target of sound-absorption coefficient αN at frequency fN with a 1/N target mold, its target strength is reduced to ΔTSN at frequency fN in the anechoic tank test. If a full-scale target is assumed that lay anechoic tiles with sound-absorption coefficient α0 at frequency f0, its target strength is reduced to ΔTS0 at frequency f0, and fN=Nf0 as well as αN=α0, it is ΔTS0=ΔTSN. It is evident from the elliptic cylinder test in the anechoic tank that this conclusion is correct to put the target in a lateral place.
A new method for measurement of pulse wave velocity in arterial wall
Authors: Zhang Xiaoming , Kinnick Randall R. , Fatemi Mostafa , Greenleaf James F.
Published: October 2013

Arterial wall stiffness can be associated with various diseases. The stiffness of an artery can be assessed by measurement of the pulse wave velocity (PWV). PWV is directly related to the Youngs modulus by the well-known Moens–Korteweg equation. Usually, PWV is estimated using the foot-to-foot method. However, the foot of the pressure wave is not very clear due to reflected waves. Also, the pressure wave is normally at a low frequency, hence, the time resolution is low. PWV is an average indicator of artery stiffness between the two measuring points, therefore it is not easy to identify local stiffness. We propose producing a very short pulse wave in the arterial wall using ultrasound radiation force and measuring its propagation speed along the artery by laser. The temporal resolution of this method is in the range of microseconds, which allows PWV to be measured accurately over a few millimeters. Experiments were carried out on a silicone tube in gelatin. PWV was measured by two scanning methods: (1) fixed source and scanning detector, (2) scanning source and fixed detector. Results: PWV was measured at 2 mm/40 μs by both methods. The Doppler technique was also tested which is potentially suitable for clinical applications.
A note on the acoustic-phonetic characteristics of non-native English vowels produced in noise
Authors: Li Chi-nin , Munro Murray J.
Published: October 2013

The Lombard reflex occurs when people unconsciously raise their vocal levels in the presence of loud background noise. Previous work has established that utterances produced in noisy environments exhibit increases in vowel duration and fundamental frequency (F0), and a shift in formant center frequencies for F1 and F2. Most studies of the Lombard reflex have been conducted with native speakers; research with second-language speakers is much less common. The present study examined the effects of the Lombard reflex on foreign-accented English vowel productions. Seven female Cantonese speakers and a comparison group of English speakers were recorded producing three vowels (/i u a/) in /bVt/ context in quiet and in 70 dB of masking noise. Vowel durations, F0, and the first two formants for each of the three vowels were measured. Analyses revealed that vowel durations and F0 were greater in the vowels produced in noise than those produced in quiet in most cases. First formants, but not F2, were consistently higher in Lombard speech than in normal speech. The findings suggest that non-native English speakers exhibit acoustic-phonetic patterns similar to those of native speakers when producing English vowels in noisy conditions.
Laboratory measurements of the 1st and 2nd moments of propagation through bubbles in a flow
Authors: Weber Thomas , Bradley David , Culver R. Lee , Lyons Anthony
Published: October 2013

The classic theory describing the change in soundspeed and attenuation for waves propagating in bubbly fluids (i.e., the 1st moment of the multiple scattering solution) can be viewed as a statement about the average pressure observed over all possible configurations of bubble position and size. The 2nd moment can also be predicted using the multiple scattering formulation, and both moments can be found independent of any knowledge of the fluid dynamic conditions controlling the mixing of bubbles. Characteristics of the fluid dynamics do appear in the time scales associated with this mixing, however, and this should be reflected in the time scales associated with convergence to the 1st and 2nd moments. This was explored by conducting propagation experiments in a tank filled with bubble-laden water that was subjected to varying flow conditions. Frequency dependent attenuation measurements were made and inverted for the bubble size distribution so that predictions of the 2nd moment could be compared to the observed quantities. High ping rates and long data records were used to observe the flow-dependent time scales associated with the measurements. The results of these experiments will be presented and discussed. [Work supported by ONR Code 321US. First author supported by a National Defense Science and Engineering Graduate Fellowhip.]
An investigation of perceptual tolerance limits of stop constriction regions along the vocal tract
Authors: Li Kang , Story Brad
Published: October 2013

In this study we explore the perceptual categories of constriction regions along the vocal tract for voiced stop consonants /b/, /d/, and /g/. The three consonants were imbedded in consonant-vowel (CV) syllables. Using an area function model, a series of stop-vowel syllables that differed only in the place of constriction at even spaces was constructed. A second series was generated by eliminating the third formant of each syllable in the first series. It was predicted that the continuum of place of constriction would result in the discontinuity of acoustic representation and the categorical perception. The predicted perception of each synthesized syllable was based on their spectrographic shapes. The results showed that the perception of the constriction continuum was categorical in both series. The boundaries of actually perceived regions agree reasonably well with the predicted ones. It turned out that the perception of the midway stimuli between two categories was ambiguous instead of being perceived as a member of one category or the other. The Distinctive Region Model based on the sensitivity function is discussed to explore a possible explanation for the ambiguity.
Control room design: An analytic perspective
Authors: Jones Douglas
Published: October 2013

The recording studio control room is a special case of small room. In this paper the subjective attributes of a control room and their objective counterparts will be explored, discussing the analytic tools that might be used to evaluate and predict the subjective performance. A number of areas where more research is needed will also be identified.
Accent, intelligibility, and comprehensibility in the perception of foreign-accented Lombard speech
Authors: Li Chi-nin
Published: October 2013

Speech produced in noise (Lombard speech) has been reported to be more intelligible than speech produced in quiet (normal speech). This study examined the perception of non-native Lombard speech in terms of intelligibility, comprehensibility, and degree of foreign accent. Twelve Cantonese speakers and a comparison group of English speakers read simple true and false English statements in quiet and in 70 dB of masking noise. Lombard and normal utterances were mixed with noise at a constant signal-to-noise ratio, and presented along with noise-free stimuli to eight new English listeners who provided transcription scores, comprehensibility ratings, and accent ratings. Analyses showed that, as expected, utterances presented in noise were less well perceived than were noise-free sentences, and that the Cantonese speakers’ productions were more accented, but less intelligible and less comprehensible than those of the English speakers. For both groups of speakers, the Lombard sentences were correctly transcribed more often than their normal utterances in noisy conditions. However, the Cantonese-accented Lombard sentences were not rated as easier to understand than was the normal speech in all conditions. The assigned accent ratings were similar throughout all listening conditions. Implications of these findings will be discussed.
ANSI S12.60 (2002) testing of modular buildings used as classrooms
Authors: Busch Todd A.
Published: October 2013

The acoustics of modular buildings used as classrooms may come under greater scrutiny if schools adopt American National Standards Institute (ANSI) S12.60 (2002) ‘‘Acoustical Performance Criteria, Design Requirements, and Guidelines for Schools’’ as required thresholds of performance. To quantify the benefits of series of structural improvements to buildings having an interior volume of less than 10000 ft3, both the reverberation time and background noise were measured. Interior spaces were unoccupied as per S12.60, but unfurnished. Reverberation times were 0.4–0.6 s. The background noise level was measured to identify the contributions of exterior sources, interior fluorescent lighting, and AC/Fan systems operating with/without a plenum for the return vent. Targets for the stated room volume are 35 dBA and 55 dBC. For the final configuration, interior noise levels with lights, fan, and cooling active were 43 dBA and 67 dBC; interior noise levels due to exterior sources were 33 dBA and 58 dBC due in part to the surrounding industrial land uses and nearby freeway. For one configuration, with the fan active without AC, pressurized air escaping through a 1/4-in. gap beneath the 36-in.-wide door produced a distinct 35 dBA tone in the 630-Hz third-octave band.
Analysis of community response to transportation noise a quarter century after Schultz (1978)
Authors: Fidell Sanford
Published: October 2013

Transportation noise is a vexing and intrinsically controversial problem that has plagued societies since the beginnings of urban civilization. A function relating cumulative noise exposure to the prevalence of noise-induced annoyance [T. J. Schultz, ‘‘Synthesis of social surveys on noise annoyance,’’ J. Acoust. Soc. Am. 64, 377–405 (1978)] is the foundation for contemporary analyses of transportation noise effects on communities. The expenditures of billions of dollars in airplane ticket and fuel taxes for the construction of an airport infrastructure and for the mitigation of noise impacts in the United States are governed by policies ostensibly supported by a successor to Schultz’s original ‘‘synthesis’’ curve. Many have grown so comfortable with the last quarter century’s paradigm for transportation noise assessment and regulation, however, that they have lost sight of its underpinnings and limitations. A review of the historical and modern states of the art identifies persistent unresolved problems in the prediction and explanation of community response to transportation noise that are not fully addressed by descriptive dosage-effect analysis.
The stability of the time-reversal process in a fluctuating ocean
Authors: Edelmann G. F. , Kim S. , Hodgkiss W. S. , Kuperman W. A. , Song H. C.
Published: October 2013

Changes in the thermocline perturb the acoustic horizontal wave numbers and to a less extent the mode shapes. The measured acoustic field is the combination of modes and phase terms dependent on these wave numbers. Without a full water column spanning time-reversal mirror, inter-modal destructive and constructive interference patterns produce seemingly unpredictable measured fields. As demonstrated in simulation, the field produced by a time-reversal mirror is robust to internal wave perturbation. [Work supported by ONR.]
Noise codes for residential spaces in Los Angeles
Authors: Raichel Daniel R.
Published: October 2013

The State of California is rather unique in using the community noise equivalent level (CNEL) rating to assess the amount of environmental noise transmission into buildings, not just to apply this index to gauge airport noise. When residential housing units in Los Angeles undergo construction or renovation, a certificate of housing compliance must be obtained before tenants or condominium owners are allowed to move in, in accordance with the provisions of Section 91.0318 of the Los Angeles municipal code. As a part of the application procedure for the certificate, a licensed acoustical engineer must prepare an acoustical report that describes the type of construction between dwelling units and the general sound attenuating properties of such construction, including hard numbers for sound attenuation between dwelling units. A field sound transmission class (FSTC) test is mandated, with a minimum required FSTC rating of 45 between the walls of adjacent units. If the FSTC test is not passed, remedial action must be taken so that the proper amount of acoustic insulation is achieved between the dwelling units.
Antidiabetic Sulfonylureas and cAMP Cooperatively Activate Epac2A
Authors: Takahashi Toshimasa , Shibasaki Tadao , Takahashi Harumi , Sugawara Kenji , Ono Aika , Inoue Naoko , Furuya Toshio , Seino Susumu
Published: October 2013

Identification of the binding site of Epac2A for an antidiabetic drug may enable the development of improved therapies.
Therapeutic Efficacy of SQ641-NE against Mycobacterium tuberculosis
Authors: Nikonenko Boris , Reddy Venkata M. , Bogatcheva Elena , Protopopova Marina , Einck Leo , Nacy Carol A.
Published: October 2013

A phospholipid-based nanoemulsion formulation of SQ641 (SQ641-NE) was active against intracellular
Mycobacterium tuberculosis
in J774A.1 mouse macrophages, although SQ641 by itself was not. Intravenous (i.v.) SQ641-NE was cleared from circulation and reached peak concentrations in lung and spleen in 1 h. In a murine tuberculosis (TB) model, 8 i.v. doses of SQ641-NE at 100 mg/kg of body weight over 4 weeks caused a 1.73 log
10
CFU reduction of
M. tuberculosis
in spleen and were generally bacteriostatic in lungs.
A Novel Dengue Virus Inhibitor, BP13944, Discovered by High-Throughput Screening with Dengue Virus Replicon Cells Selects for Resistance in the Viral NS2B/NS3 Protease
Authors: Yang Chi-Chen , Hu Han-Shu , Wu Ren-Huang , Wu Szu-Huei , Lee Shiow-Ju , Jiaang Weir-Torn , Chern Jyh-Haur , Huang Zhi-Shun , Wu Huey-Nan , Chang Chung-Ming , Yueh Andrew
Published: October 2013

Dengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year. No effective DENV vaccine is available, and the current treatment is only supportive. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified a potential small-molecule inhibitor, BP13944, via high-throughput screening (HTS) of 60,000 compounds using a stable cell line harboring an efficient luciferase replicon of DENV serotype 2 (DENV-2). BP13944 reduced the expression of the DENV replicon reporter in cells, showing a 50% effective concentration (EC
50
) of 1.03 ± 0.09 μM. Without detectable cytotoxicity, the compound inhibited replication or viral RNA synthesis in all four serotypes of DENV but not in Japanese encephalitis virus (JEV). Sequencing analyses of several individual clones derived from BP13944-resistant RNAs purified from cells harboring the DENV-2 replicon revealed a consensus amino acid substitution (E66G) in the region of the NS3 protease domain. Introduction of E66G into the DENV replicon, an infectious DENV cDNA clone, and recombinant NS2B/NS3 protease constructs conferred 15.2-, 17.2-, and 3.1-fold resistance to BP13944, respectively. Our results identify an effective small-molecule inhibitor, BP13944, which likely targets the DENV NS3 protease. BP13944 could be considered part of a more effective treatment regime for inhibiting DENV in the future.
Activity of and Effect of Subcutaneous Treatment with the Broad-Spectrum Antiviral Lectin Griffithsin in Two Laboratory Rodent Models
Authors: Barton Christopher , Kouokam J. Calvin , Lasnik Amanda B. , Foreman Oded , Cambon Alexander , Brock Guy , Montefiori David C. , Vojdani Fakhrieh , McCormick Alison A. , O'Keefe Barry R. , Palmer Kenneth E.
Published: October 2013

Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.
Amidate Prodrugs of 9-[2-(Phosphonomethoxy)Ethyl]Adenine as Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis
Authors: Šmídková Markéta , Dvořáková Alexandra , Tloušt'ová Eva , Česnek Michal , Janeba Zlatko , Mertlíková-Kaiserová Helena
Published: October 2013

Adenylate cyclase toxin (ACT) is the key virulence factor of
Bordetella pertussis
that facilitates its invasion into the mammalian body. 9-[2-(Phosphonomethoxy)ethyl]adenine diphosphate (PMEApp), the active metabolite of the antiviral drug bis(POM)PMEA (adefovir dipivoxil), has been shown to inhibit ACT. The objective of this study was to evaluate six novel amidate prodrugs of PMEA, both phenyloxy phosphonamidates and phosphonodiamidates, for their ability to inhibit ACT activity in the J774A.1 macrophage cell line. The two phenyloxy phosphonamidate prodrugs exhibited greater inhibitory activity (50% inhibitory concentration [IC
50
] = 22 and 46 nM) than the phosphonodiamidates (IC
50
= 84 to 3,960 nM). The inhibitory activity of the prodrugs correlated with their lipophilicity and the degree of their hydrolysis into free PMEA in J774A.1 cells. Although the prodrugs did not inhibit ACT as effectively as bis(POM)PMEA (IC
50
= 6 nM), they were significantly less cytotoxic. Moreover, they all reduced apoptotic effects of ACT and prevented an ACT-induced elevation of intracellular [Ca
2+
]i. The amidate prodrugs were less susceptible to degradation in Caco-2 cells compared to bis(POM)PMEA, while they exerted good transepithelial permeability in this assay. As a consequence, a large amount of intact amidate prodrug is expected to be available to target macrophages
in vivo
. This feature makes nontoxic amidate prodrugs attractive candidates for further investigation as novel antimicrobial agents.
The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumoniae
Authors: Ferrándiz María-José , de la Campa Adela G.
Published: October 2013

We studied the transcriptomic response of
Streptococcus pneumoniae
to levofloxacin (LVX) under conditions inhibiting topoisomerase IV but not gyrase. Although a complex transcriptomic response was observed, the most outstanding result was the upregulation of the genes of the
fatDCEB
operon, involved in iron (Fe
2+
and Fe
3+
) uptake, which were the only genes varying under every condition tested. Although the inhibition of topoisomerase IV by levofloxacin did not have a detectable effect in the level of global supercoiling, increases in general supercoiling and
fatD
transcription were observed after topoisomerase I inhibition, while the opposite was observed after gyrase inhibition with novobiocin. Since
fatDCEB
is located in a topological chromosomal domain downregulated by DNA relaxation, we studied the transcription of a copy of the 422-bp (including the P

fat

promoter) region located upstream of
fatDCEB
fused to the
cat
reporter inserted into the chromosome 106 kb away from its native position: P

fat

fatD
was upregulated in the presence of LVX in its native location, whereas no change was observed in the P

fat

cat
construction. Results suggest that topological changes are indeed involved in P

fat

fatDCE
transcription. Upregulation of
fatDCEB
would lead to an increase of intracellular iron and, in turn, to the activation of the Fenton reaction and the increase of reactive oxygen species. In accordance, we observed an attenuation of levofloxacin lethality in iron-deficient media and in a strain lacking the gene coding for SpxB, the main source of hydrogen peroxide. In addition, we observed an increase of reactive oxygen species that contributed to levofloxacin lethality.
Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells
Authors: Sharma Biswa Nath , Marschall Manfred , Henriksen Stian , Rinaldo Christine Hanssen
Published: October 2013

Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 μM. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2′-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G
0
or G
2
phase. Both the antiproliferative and antiviral effects of artesunate at 10 μM were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.
Sensory and motor deficits exist on the non-injured side of patients with unilateral tendon pain and disability—implications for central nervous system involvement: a systematic review with meta-analysis
Authors: Heales L J , Lim E C W , Hodges P W , Vicenzino B
Published: October 2013

Introduction

Tendinopathy manifests as activity-related tendon pain with associated motor and sensory impairments. Tendon tissue changes in animals present in injured as well as contralateral non-injured tendon. This review investigated evidence for bilateral sensory and motor system involvement in unilateral tendinopathy in humans.

Methods

A comprehensive search of electronic databases, and reference lists using keywords relating to bilateral outcomes in unilateral tendinopathy was undertaken. Study quality was rated with the Epidemiological Appraisal Instrument and meta-analyses carried out where appropriate. Analysis focused on comparison of measures in the non-symptomatic side of patients against pain-free controls.

Results

The search revealed 5791 studies, of which 20 were included (117 detailed reviews, 25 met criteria). There were 17 studies of lateral epicondylalgia (LE) and one each for patellar, Achilles and rotator cuff tendinopathy. Studies of LE were available for meta-analysis revealing the following weighted pooled mean deficits: pressure pain thresholds (−144.3 kPa; 95% CI −169.2 to −119.2 p<0.001), heat pain thresholds (−1.2°C; 95% CI −2.1 to −0.2, p<0.001), cold pain thresholds (3.1°C; 95% CI 1.8 to 4.4, p<0.001) and reaction time (37.8 ms; 95% CI 24.8 to 50.7, p<0.001).

Discussion

Deficits in sensory and motor systems present bilaterally in unilateral tendinopathy. This implies potential central nervous system involvement. This indicates that rehabilitation should consider the contralateral side of patients. Research of unilateral tendinopathy needs to consider comparison against pain-free controls in addition to the contralateral side to gain a complete understanding of sensory and motor features.
Adherence of bacteria to mucus collected from different parts of the reproductive tract of heifers and cows
Authors: Styková E. , Nemcová R. , Valocký I. , Novotný F. , Guba P.
Published: October 2013

In the present study, we examined the adherence of indigenous vaginal bacteria, probiotic strains, and metritis pathogens to mucus collected from different parts of the reproductive tracts of heifers and cows and compared their adherence with the bacterial adherence to mucus collected from the stomach and large intestine of pigs. Most of the vaginal strains adhered to mucus collected from different parts of the reproductive tract and strongly adhered to gastric mucus, with the exception of Lactobacillus buchneri 24S8. Only Lactobacillus mucosae 29S8, Enterococcus faecium E21, and E. faecium EAC adhered to colonic mucus. Probiotic strains adhered strongly to mucus collected from the reproductive tract and gastric mucus but did not adhere to colonic mucus. Pathogenic strains were adherent to vaginal, uterine horn, and gastric mucus, except Escherichia coli O8:K88ab:H9 (65), Fusobacterium necrophorum, and Gardnerella vaginalis, which adhered to uterine cervix mucus. Only Kocuria kristinae and G. vaginalis adhered to uterine body mucus; E. coli O149:K88ac (EC) adhered to colonic mucus. The strains did not exhibit host specificity but rather strain specificity. The ability to adhere to mucus was a characteristic unique to each strain. To our knowledge, this is the first report regarding in vitro adherence of GRAS (Generally Regarded As Safe) lactobacilli isolated from different sources to mucus collected from different parts of the reproductive tract.
Fluctuation analysis and short time asymptotics for multiple scales diffusion processes
Authors: Spiliopoulos Konstantinos
Published: October 2013

We consider the limiting behavior of fluctuations of small noise diffusions with multiple scales around their homogenized deterministic limit. We allow full dependence of the coefficients on the slow and fast motion. These processes arise naturally when one is interested in short time asymptotics of multiple scale diffusions. We do not make periodicity assumptions, but we impose conditions on the fast motion to guarantee ergodicity. Depending on the order of interaction between the fast scale and the size of the noise, we get different behavior. In certain cases additional drift terms arise in the limiting process, which are explicitly characterized. These results provide a better approximation to the limiting behavior of such processes when compared to the law of large numbers homogenization limit.
EVALUATION OF THE T-STRESS FOR MULTIPLE CRACKS IN AN INFINITE PLATE USING SINGULAR INTEGRAL EQUATION
Authors: CHEN Y. Z. , WANG Z. X.
Published: October 2013

This paper studies T-stress problem for multiple cracks in an infinite plate with the remote loading. After some manipulations, the problem can be modeled by dislocation distributions along the crack faces. A singular integral equation is formulated for the problem, where the unknowns are the dislocation distribution along the crack faces. The SIFs (stress intensity factor) can be evaluated from the solution of singular integral equation. From a definition for T-stress in the crack back position method and the solution of the singular integral equation, the T-stresses at crack tips can be evaluated accordingly. An explicit formula for the T-stress is provided. Several numerical examples are provided. Accuracy of computation is examined by an example.
Use of the Vascularized Iliac-Crest Flap in Musculoskeletal Lesions
Authors: Tonoli Cristiane , Bechara Alexandre H. S. , Rossanez Roberto , Belangero William D. , Livani Bruno
Published: October 2013

Bone loss was in the past treated by several methods, such as bone distraction and the use of nonvascularized or tissue-bank bone grafts. With the advent of modern microsurgical techniques, the vascularized bone flap has been used with good results; it resolves local nutritional problems, repairs soft tissue that is often damaged by severe trauma, and treats bone loss due to tumors, pseudarthroses, and osteomyelitis. This paper reports the authors’ experience with the use of vascularized iliac-crest flaps to treat orthopedic pathologies in five patients with traumatic bone loss (<10 cm), three with osteomyelitis, and three with atrophic nonunion. In all cases, the same surgeon obtained a vascularized iliac-crest flap with a pedicle based on the deep iliac circumflex artery. All flaps consolidated within a mean period of 3 months. These findings demonstrate that the use of an iliac-crest flap is a treatment option in cases of bone loss and that it is associated with good functional results and minimal donor-site morbidity.
Usefulness of Image Guidance in the Surgical Treatment of Petrous Apex Cholesterol Granuloma
Authors: Pietrantonio A. , D’Andrea G. , Famà I. , Volpini L. , Raco A. , Barbara M.
Published: October 2013

The petrous apex is a pyramid-shaped structure, located medial to the inner ear and the intrapetrous segment of the internal carotid artery. Lesions of the petrous apex can be surgically treated through different surgical routes. Because of the important neurovascular structures located inside the temporal bone, anatomical 3D knowledge is paramount. For this reason, image-guided surgery could represent a useful tool. We report the case of a young woman who came to our observation for a trigeminal neuralgia due to a petrous apex cholesterol granuloma. The lesion was treated through the placement of a drainage tube via an infracochlear approach, with the aid of neuronavigation and intraoperative MRI. Preoperative CT scan images and intraoperative MRI images were fused for surgical planning. The accuracy of the neuronavigation system has proved to be good, and the safety of the procedure was enhanced. Therefore, neuronavigation and intraoperative MRI, though not available in all neurootological centres, should be considered useful tools in these challenging procedures.
Fatigue and Sleep-Disordered Breathing in Multiple Sclerosis: A Clinically Relevant Association?
Authors: Kallweit Ulf , Baumann Christian R. , Harzheim Michael , Hidalgo Hildegard , Pöhlau Dieter , Bassetti Claudio L. , Linnebank Michael , Valko Philipp O.
Published: October 2013

Background. Fatigue in patients with multiple sclerosis (MS) is highly prevalent and severely impacts quality of life. Recent studies suggested that sleep-disordered breathing (SDB) significantly contributes to fatigue in MS.Study Objective. To evaluate the importance of routine respirography in MS patients with severe fatigue and to explore the effects of treatment with continuous positive airway pressure (CPAP).Patients and Methods. We prospectively assessed the presence of severe fatigue, as defined by a score of ≥5.0 on the Fatigue Severity Scale (FSS), in 258 consecutive MS patients. Ninety-seven patients (38%) suffered from severe fatigue, whereof 69 underwent overnight respirography.Results. We diagnosed SDB in 28 patients (41%). Male sex was the only independent associate of SDB severity (P=0.003). CPAP therapy in 6 patients was associated with a significant reduction of FSS scores (5.8±0.5versus4.8±0.6,P=0.04), but the scores remained pathological (≥4.0) in all patients.Conclusion. Respirography in MS patients with severe fatigue should be considered in daily medical practice, because SDB frequency is high and CPAP therapy reduces fatigue severity. However, future work is needed to understand the real impact of CPAP therapy on quality of life in this patient group.