bluuebunny/crossref_metadata_2025 huggingface dataset:
A simplified method for approximating the natural frequencies of acoustic-structure systems
Authors: Davis R. Benjamin
Published: September 2008

It is well known that the natural frequency of a flexible structure in contact with a fluid-filled cavity can be approximated with a closed-form expression that considers the coupling of only two component modes (i.e., a rigid-wall acoustic mode and an in vacuo structural mode) [F. Fahy, Sound and Structural Vibration (Academic, London, 1985), Chap. 6, pp. 249–256]. However, this expression requires volume and area integrations over the component mode shapes. For many practical configurations, the effort to determine the component mode shapes and compute the necessary integrals counteracts much of the time and computational savings afforded by the closed-form expression. Here, the closed-form expression is recast as a function of the nondimensional frequency separation between the component modes and a new nondimensional coupling parameter, Ψ. Design curves representing the value of Ψ for common geometries and boundary conditions are presented. With the use of these design curves and a knowledge of the component modes frequencies, one can quickly compute reasonable approximations of the coupled natural frequencies by hand.
Vibration of circular plate and its frequency parameters
Authors: GE Li-Feng
Published: September 2008

The vibration of circular plates with inplane forces has been classically discussed [T. Wah, J. Acoust. Soc. Am. 34(3), 275–281, 1962, and A. Leissa, Vibration of Plates, ASA, 1993, originally, NASA, 1969]. In these literatures each of two characteristic values is expressed as a function of two stiffness factors, i.e., the inplane tension and the bending stiffness of the plate. The author has extended it to a general case in which the stretched plate is also supported by a massless elastic medium (or foundation). The corresponding two characteristic values are expressed as a function of three stiffness factors, which includes an additional stiffness of the foundation [L.-F. Ge, 16th ICA/135th ASA Meeting, Proc. 1081-1082, 1998, and J. Acoust. Soc. Am. 103, 2870, 1998]. In this paper the two characterized values and the frequency parameter have been calculated and checked further. It is found that some values given in the previous literatures have some errors, the biggest one of which is 4.0%. Furthermore, this paper developed a 3-D plot of the characterized values, and gave the corrected tables of the characterized values and frequency parameter for both simply supported and clamped plates. [Work supported by NSFC (60374044).]
Compensatory responses to unexpected jaw loading during speech observed with magnetometry
Authors: Tiede Mark , Ito Takayuki , Ostry David
Published: September 2008

Observations were made of articulator and formant trajectories during speech perturbed by unexpected mechanical loads applied to the jaw. Subjects produced multiple repetitions of the phrase ‘‘see X avis,’’ where X was one of ‘‘raw,’’ ‘‘rob’’ or ‘‘rod.’’ Perturbation forces were applied using a jaw-coupled robot, and triggered using a thresholding criterion applied to real-time tracking of the initial low to high transition in the first formant. Perturbations were delivered one out of every five repetitions, selected at random, with half applied upwards and half downwards, and forces sustained throughout the remainder of the utterance. Three EMMA sensors located on the anterior midsagittal surface of the tongue in addition to lower mandibular and upper lip sensors were used to track articulator positions. Audio and surface EMG (masseter, ABD, and OOS) were collected concurrently. Formants show initial deviation from control trajectories and then recovery that begins approximately 75 ms after the onset of perturbation. Compensation in most instances is nearly complete, even though jaw position does not recover its unperturbed trajectory. Perturbed tongue sensor trajectories are strongly distinguished by coda type, but show a pattern converging on the unperturbed tongue shape consistent with the tongue’s presumed role in effecting formant recovery.
Sensory movement goals and control mechanisms in speech production
Authors: Perkell Joseph
Published: September 2008

An overview of speech production is described in which the goals of phonemic speech movements are implemented in auditory and somatosensory domains and the movements are controlled by a combination of feedback and feedforward mechanisms. Findings of motor-equivalent trading relations in producing /u/ and /r/, cross-speaker relations between vowel and consonant production and perception, and speakers use of a saturation effect in producing /s/ support the idea that the goals are in sensory domains. Results of production experiments in which auditory feedback was modified and interrupted, provide insight into the nature of feedback and feedforward control mechanisms. The findings are all compatible with the DIVA model of speech motor planning [Guenther et al., Brain & Language 96, 280–301(2006)], which makes it possible to quantify relations among phonemic specifications of utterances, brain activity, articulatory movements, and the speech sound output. [Research supported by NIDCD/NIH.]
How is auditory feedback processed during speaking?
Authors: Houde John F. , Nagarajan Srikantan S.
Published: September 2008

Several studies have shown that speaking suppresses the normal response to speech sounds in auditory cortex and associated regions. Our own studies using magnetoencephalography (MEG) suggest a model of how auditory feedback is processed during speaking where speaking-induced suppression (SIS) arises from a comparison between actual auditory input and a prediction of that auditory input. Over the past several years, we have been testing this model in various experiments. We have studied the specificity of SIS by examining how SIS is modulated by different types of feedback alterations. We have also looked at how choice of speech target produced modulates SIS. Our model also makes predictions about how auditory cortex would respond to transient perturbations of speech feedback, which we have tested in experiments examining the auditory response to pitch feedback perturbations. Finally, we postulate that our model of speech feedback processing is really just a special case of how auditory feedback is processed in all motor tasks with associated auditory feedback. Our recent experiments looking at responses to auditory stimuli induced by a self-initiated motor acts are consistent with this more general interpretation of our model. [Work supported by NSF Grant No. BCS-0349582 and NIH/NIDCD Grant No. R01-DC006435.]
A neuroimaging investigation of auditory-motor learning
Authors: Reilly Kevin J. , Guenther Frank H. , Tourville Jason A. , Bohland Jason W.
Published: September 2008

Brain activity was measured in 11 subjects while learning a novel speech-like auditory-motor task. Subjects learned to move a dot on a screen to one of three target locations by changing their formant frequencies during production of vowel-like sounds. The targets corresponded to regions of the formant space not associated with American English vowels. Functional images were acquired using a sparse sampling technique that allowed performance of the task in the absence of scanner noise and avoided artifactual signal changes resulting from articulator movements. The accuracy of subjects’ production of the novel vowel sounds increased significantly over the course of the scanning session. Significant correlations between performance error and brain activity were observed in a number of areas, including superior temporal gyrus, inferior frontal gyrus, primary motor cortex, supplementary motor area, and medial and lateral cerebellum. Brain regions exhibiting a positive correlation with performance error were generally consistent with regions that have been associated with feedback error detection/correction for the production of learned speech sounds. Greater right hemisphere activation of frontal and temporal areas raises the possibility of hemispheric specialization for this aspect of speech motor control.
Performance analysis and modeling of underwater acoustic communications at low input signal-to-noise ratios using direct sequence spread spectrum
Authors: Yang T.C. , Yang Wen-Bin
Published: September 2008

Direct sequence spread spectrum (DSSS) uses a code sequence to spread the symbols at the transmitter and a de-spreader at the receiver to recover the transmitted symbols. The de-spreader (a correlator or a matched filter) provides a processing gain (matched filter gain), which enhances the symbol energy over noise, thus allowing communications at low input signal-to-noise ratio (SNR). For underwater communications, additional processing is needed to mitigate the effect of the rapid temporal fluctuation of the propagation channel. This paper analyzes DSSS data collected during the TREX04 experiment, which uses an m-sequence as the spreading code. More than 1,000 packets have been analyzed at input SNR, varying from −15 dB to +23 dB. Zero-bit errors were achieved for input SNR as low as −8 to −10 dB for two processors used. Performance loss due to inaccurate synchronization, inaccurate channel estimation, and signal fading are quantitatively modeled as a function of decreasing SNR. [Work supported by ONR.]
The analogy between acoustic holography and sound field reproduction
Authors: Chang Ji-Ho , Kim Yang-Hann
Published: September 2008

Acoustic holography is to predict sound field by sound pressure values on measurement plane while sound field reproduction is to generate sound field by loudspeakers. They have absolutely different objectives but handle sound field so that they have a common mathematical approach according to the shape of the sound field of interest. Hence several methods of sound field reproduction, WFS, ambisonics, BPC, mode matching method, etc., correspond with each category of acoustic holography: plane holography, cylindrical holography and spherical holography, etc. In this paper, mathematical and technical similarities are introduced and discussed. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the National Research Lab. Program funded by the Ministry of Science and Technology (M10500000112-05J0000-11210).]
Alternative closeness functions for eye microphone array
Authors: Alghassi Hedayat , Tafazoli Shahram , Lawrence Peter
Published: September 2008

A new signal processing algorithm, accompanied by a novel hemispherical microphone array structure for sound source localization in three-dimensional spaces was presented [H. Alghassi et al., ‘‘Acoustic source localization with eye array,’’ JASA 120(5) (2006)]. This localization methodology, which has some analogy to the eye in localization of light rays, uses concepts of two-microphone (pinhole) or three-microphone (lens) cell structures alongside a special closeness function (CF) to approximate the proximity of the sound source direction to each of the hemisphere microphone directions based on particular similarity measures among signals. The CF plays a major role in the accuracy of the final source direction estimation. The earlier multiplicative CF (MCF) operates based on vector multiplication of spatial derivative and time derivative of microphone signals. This work presents two additional categories of CFs and compares them with MCF. The difference CF (DCF) is based on subtraction of delayed reference signal and shell microphone signals, while the correlative CF (CCF) is based on multiplication of delayed reference signal and shell microphone signals. Similar to MCF, both DCF and CCF perform demonstrated linear output versus deviation angle. Although DCF and MCF have not shown improved experimental accuracy compared to MCF, they attained lower computational complexity.
On-line failure detection of a vibrating structure: A model-based approach
Authors: Guidry B. L. , Candy J. V. , Fisher K. A. , Chambers D. H. , Lehman S. K.
Published: September 2008

Model-based failure detection is based on the principle that the MBP for a normal or pristine structure is developed first and tuned during the calibration stage assuring a statistically validated processor. Once developed, the MBP is used as the integral part in a sequential detection scheme to decide whether or not the structure under investigation is operating normally. When an abnormality is detected, a failure alarm is activated and the type of failure is classified based on a library of potential failure modes. Here we use high-order parametric models to capture the essence of the structures over a limited frequency band known to be sensitive to structural changes. These estimated or identified models for normal operations are then used to develop the MBP which in this instance is a recursive Kalman filter. The filter is known to produce zero-mean/white residuals when optimally tuned to the data. Failure is declared when these properties are no longer valid. Once the detection is accomplished, the next step is to classify the type of failure mechanism and eventually the locations. Here we show results of the designs on both simulated and measured data.
Fault localization of moving machinery in a noisy environment
Authors: Jeon Jong-Hoon , Park Choon-Su , Kim Yang-Hann
Published: September 2008

Faults of rotating parts of a machine normally generate unexpected frequency band or impulsive sound, which has a period when it moves with a constant speed. The former can be detected by the moving frame acoustic holography method [S.-H. Park and Y.-H. Kim, ‘‘An improved moving frame acoustic holography for coherent bandlimited noise,’’ J. Acoust. Soc. Am. 104, 3179–3189 (1998)]. We have attempted to apply the method to the latter case in the test site. The keywords are, therefore, the periodic impulsive sound, which is obviously different from those which can be visualized by the method, and the signal-to-noise ratio, which determines the success of early-fault detection. This research shows how the problems related with these keywords can be resolved. The main idea is that periodic impulsive signal can be expressed by an infinite set of discrete pure tones. This enables us to obtain alot of holograms that visualize periodic impulsive sound field and noise; therefore, holograms can be averaged to improve the signal-to-noise ratio until having reliable information that exhibits where the impulsive sources are. Theory, experiment, and application results to the train on a test rig are described. [Work supported by BK21 and KRRI.]
Reverberation modeling issues highlighted by the first Reverberation Modeling Workshop
Authors: Thorsos Eric I. , Perkins John S.
Published: September 2008

Participants at Reverberation Modeling Workshop I presented solutions to posed reverberation problems using a wide variety of methods. The reverberation problems were posed in both two- and three-space dimensions, and included cases with different levels of boundary roughness, different sound speed profiles, and in some cases, range dependence. A number of important reverberation modeling issues became evident when the results of this workshop were considered in detail following the workshop. These include the important role of coherent effects in determining reverberation structure at short ranges, and the important role of boundary reflection loss in affecting the reverberation level at long ranges. A summary of modeling issues highlighted by this workshop will be presented. [Work supported by ONR and PMW-180.]
A comparison of two modeling approaches for reverberation in a shallow-water waveguide where the scattering arises from a sub-bottom interface
Authors: Ellis Dale D. , Holland Charles W.
Published: September 2008

In shallow water environments with a low-speed sediment layer overlying a higher-speed sub-bottom, the observed reverberation may be dominated by scattering from the sub-bottom. Here, reverberation predictions from normal mode and energy flux models are compared for the case where the scattering arises from a sub-bottom half-space under the low-speed sediment layer. It is shown that in such an environment, the position of the angle of intromission, in addition to the angular dependence of the scattering kernel, is a factor controlling the vertical angle distribution. It is also shown that the reverberation from a sub-bottom horizon is typically governed by higher grazing angles than the case where the scattering occurs at the water-sediment interface. There was generally very close agreement between the models as a function of frequency (200–1,600 Hz), layer thickness (0–8 m), and range (1–15 km). The model comparisons, showing some differences, illuminate the effect of different approximations in the two approaches. [Work supported in part by the Office of Naval Research.]
Frequency and angular dependence of bottom scattering strength in shallow water with a sandy seabed
Authors: Zhou Ji-Xun , Zhang Xue-Zhen
Published: September 2008

The bottom scattering strength at low frequencies and small grazing angles is difficult to directly measure in shallow water. It is generally derived from mid- and long-range reverberation measurements. Reliable estimation of the bottom scattering strength from shallow-water reverberation requires a correct reverberation model, quality reverberation data, and an appropriate seabed geo-acoustic model that controls two-way sound propagation. In this paper, an effective Biot model for sand-silt bottoms, derived from low-frequency field measurements at 18 locations in different coastal zones around the world is used [J. X. Zhou and X. Z. Zhang, J. Acoust. Soc. Am. 117, 2494 (2005) and 119, 3447 (2006)]. A simple closed form expression for the reverberation in shallow isovelocity water [J. X. Zhou, Acta Acustica 5(2), 86–99(1980) in Chinese] as well as the normal-mode expression for the reverberation in shallow water with an arbitrary sound speed profile are used to derive the bottom scattering strength. The bottom scattering strength as a function of frequency and angle, derived from broadband reverberation data, will be reported and discussed. [Work supported by ONR.]
High frequency acoustic bottom backscatter at shallow grazing angles
Authors: Chotiros Nicholas P.
Published: September 2008

Variability is an important feature of high frequency acoustic bottom backscatter. A relationship had been developed between grain-size and backscattering strength in the laboratory, but it rarely applies in the field. The main problem is that real ocean sediments have surface roughness and volume scatterers or inclusions that are continually evolving. The result is a rather large range of variations as a function of space and time. In some cases, estimates of the variability may be obtained from the extant database of published measurements. [Work supported by the Office of Naval Research, Ocean Acoustics.]
Efficacy of the Combination of Tachyplesin III and Clarithromycin in Rat Models of
Escherichia coli
Sepsis
Authors: Cirioni Oscar , Ghiselli Roberto , Silvestri Carmela , Kamysz Wojciech , Orlando Fiorenza , Riva Alessandra , Kamysz Elzbieta , Castelletti Sefora , Rocchi Marco , Saba Vittorio , Scalise Giorgio , Giacometti Andrea
Published: September 2008

We investigated the efficacy of tachyplesin III and clarithromycin in two experimental rat models of severe gram-negative bacterial infections. Adult male Wistar rats were given either (i) an intraperitoneal injection of 1 mg/kg
Escherichia coli
0111:B4 lipopolysaccharide or (ii) 2 × 10
10
CFU of
E. coli
ATCC 25922. For each model, the animals received isotonic sodium chloride solution, 1 mg/kg tachyplesin III, 50 mg/kg clarithromycin, or 1 mg/kg tachyplesin III combined with 50 mg/kg clarithromycin intraperitoneally. Lethality, bacterial growth in the blood and peritoneum, and the concentrations of endotoxin and tumor necrosis factor alpha (TNF-α) in plasma were evaluated. All the compounds reduced the lethality of the infections compared to that for the controls. Tachyplesin III exerted a strong antimicrobial activity and achieved a significant reduction of endotoxin and TNF-α concentrations in plasma compared to those of the control and clarithromycin-treated groups. Clarithromycin exhibited no antimicrobial activity but had a good impact on endotoxin and TNF-α plasma concentrations. A combination of tachyplesin III and clarithromycin resulted in significant reductions in bacterial counts and proved to be the most-effective treatment in reducing all variables measured.
Role ofampDHomologs in Overproduction of AmpC in Clinical Isolates ofPseudomonas aeruginosa
Authors: Schmidtke Amber J. , Hanson Nancy D.
Published: September 2008

AmpD indirectly regulates the production of AmpC β-lactamase via the cell wall recycling pathway. Recent publications have demonstrated the presence of multipleampDgenes inPseudomonas aeruginosaandEscherichia coli. In the prototypeP. aeruginosastrain, PAO1, the threeampDgenes (ampD,ampDh2, andampDh3) contribute to a stepwise regulation ofampCβ-lactamase and help explain the partial versus full derepression ofampC. In the present study, the roles of the threeampDhomologs in nine clinicalP. aeruginosaisolates with either partial or full derepression ofampCwere evaluated. In eight of nine isolates, decreased RNA expression of theampDgenes was not associated with an increase inampCexpression. Sequence analyses revealed that every derepressed isolate carried mutations inampD, and in two fully derepressed strains, onlyampDwas mutated. Furthermore, everyampDh2gene was of the wild type, and in some fully derepressed isolates,ampDh3was also of the wild type. Mutations inampDandampDh3were tested for their effect on function by using a plasmid model system, and the observed mutations resulted in nonfunctional AmpD proteins. Therefore, although the sequential deletion of theampDhomologs ofP. aeruginosacan explain partial and full derepression in PAO1, the same model does not explain the overproduction of AmpC observed in these clinical isolates. Overall, the findings of the present study indicate that there is still an unknown factor(s) that contributes toampCregulation inP. aeruginosa.
In Vitro Activity of Doripenem, a Carbapenem for the Treatment of Challenging Infections Caused by Gram-Negative Bacteria, against Recent Clinical Isolates from the United States
Authors: Pillar Chris M. , Torres Mohana K. , Brown Nina P. , Shah Dineshchandra , Sahm Daniel F.
Published: September 2008

Doripenem, a 1β-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of
Staphylococcus aureus
, coagulase-negative staphylococci,
Streptococcus pneumoniae
,
Enterobacteriaceae
,
Pseudomonas aeruginosa
, and
Acinetobacter
spp. MICs (μg/ml) were established by broth microdilution. By MIC
90
, doripenem was comparable to imipenem and meropenem in activity against
S. aureus
(methicillin susceptible, 0.06; resistant, 8) and
S. pneumoniae
(penicillin susceptible, ≤0.015; resistant, 1). Against ceftazidime-susceptible
Enterobacteriaceae
, the MIC
90
of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum β-lactamase screen-positive
Enterobacteriaceae
. Doripenem was the most potent carbapenem tested against
P. aeruginosa
(MIC
90
/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible
Acinetobacter
spp., doripenem (MIC
90
= 2, 89.1%S) was twice as active by MIC
90
as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against
Enterobacteriaceae
, including β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against
P. aeruginosa
regardless of β-lactam resistance.
Mucroporin, the First Cationic Host Defense Peptide from the Venom ofLychas mucronatus
Authors: Dai Chao , Ma Yibao , Zhao Zhenhuan , Zhao Ruiming , Wang Qian , Wu Yingliang , Cao Zhijian , Li Wenxin
Published: September 2008

The misuse of antibiotics has led our age to a dangerous edge, as antibiotic-resistant pathogens appear to evolve more quickly than antibiotics are invented. Thus, new agents to treat bacterial infection are badly needed. Cationic host defense peptides are on the first line of a host defense system and are thought to be good candidates for treating bacterial infection. Here, a novel cationic host defense peptide, mucroporin, was cloned and characterized from the venom ofLychas mucronatus. The MIC forStaphylococcus aureuswas 25 μg/ml, including antibiotic-resistant pathogens. Based on the molecular template of mucroporin, mucroporin-M1 was designed by amino acid substitution. The MIC forS. aureuswas 5 μg/ml, including the antibiotic-resistant pathogens methicillin-resistantS. aureus, methicillin-resistant coagulase-negativeStaphylococcus, penicillin-resistantS. aureus, and penicillin-resistantS. epidermidis. Moreover, mucroporin-M1 also inhibited gram-negative bacteria. The modes of action of mucroporin and mucroporin-M1 were both rapid killing by disrupting the cell membrane of bacteria, and the number of surviving bacteria was reduced by about 4 to 5 orders of magnitude immediately after peptide delivery. These results showed that mucroporin could be considered a potential anti-infective drug, especially for treating antibiotic-resistant pathogens.
In Vivo Microdialysis Study of the Penetration of Daptomycin into Soft Tissues in Diabetic versus Healthy Volunteers
Authors: Kim Aryun , Suecof Larry A. , Sutherland Christina A. , Gao Lihong , Kuti Joseph L. , Nicolau David P.
Published: September 2008

Daptomycin is approved for the treatment of complicated skin and soft tissue infections, including diabetic wounds of the lower extremities, at a dose of 4 mg/kg of body weight once daily. For such localized tissue infections, drug concentrations in the interstitial space are an important determinant of successful therapy. In the diabetic population, peripheral arterial disease may limit antibiotic penetration into the target tissue. The objective of this study was to describe and compare the pharmacokinetic profiles of daptomycin in the interstitial fluid of soft tissues in diabetic and healthy volunteers by using in vivo microdialysis. Twelve subjects (six diabetic and six healthy) received a single 4-mg/kg dose of daptomycin intravenously. Samples of plasma and tissue were simultaneously collected over 24 h. Diabetic and healthy groups were matched in mean age (±10 years), gender ratio, mean weight (±10 kg), and creatinine clearance rate (±20 ml/min/1.73 m
2
). Pharmacokinetic parameters for plasma were similar between groups (
P
> 0.05). The mean peak drug concentrations ± standard deviations in tissue were 4.3 ± 3.3 μg/ml and 3.8 ± 1.4 μg/ml for diabetic and healthy subjects, respectively. The degree of tissue penetration, defined as the ratio of the area under the free drug concentration-time curve for tissue to that for plasma, was 0.93 ± 0.61 for diabetic subjects and 0.74 ± 0.09 for healthy subjects (
P
= 0.46). Daptomycin at 4 mg/kg penetrated well into the soft tissue, reaching concentrations approximately 70 to 90% of those of the free drug in plasma. Moreover, these free, bioactive concentrations in tissue exceeded the MICs for staphylococci and streptococci over the 24-h dosing interval.
Effect of Concomitant Artesunate Administration and Cytochrome P4502C8 Polymorphisms on the Pharmacokinetics of Amodiaquine in Ghanaian Children with Uncomplicated Malaria
Authors: Adjei George O. , Kristensen Kim , Goka Bamenla Q. , Hoegberg Lotte C. G. , Alifrangis Michael , Rodrigues Onike P. , Kurtzhals Jorgen A. L.
Published: September 2008

Artesunate (AS) is used in combination with amodiaquine (AQ) as first-line treatment for uncomplicated malaria in many countries. We investigated the effect of concomitant AS administration on the pharmacokinetics of AQ and compared concentrations of desethylamodiaquine (DEAQ), the main metabolite of AQ, in plasma between patients with different variants of the cytochrome P4502C8 (CYP2C8) gene. A two-compartment model was fitted to 169 plasma DEAQ concentrations from 103 Ghanaian children aged 1 to 14 years with uncomplicated malaria treated either with AQ alone (n= 15) or with AS plus AQ (n= 88). The population clearance of DEAQ appeared to increase nonlinearly with body weight, and the central volume of distribution of DEAQ was higher (P< 0.001) in the AS-plus-AQ group than in the AQ-only group. The maximum plasma DEAQ concentration was higher (P< 0.001), and the population distribution half-life was shorter (P< 0.01), in the AQ-only group than in the AS-plus-AQ group. The total areas under the plasma DEAQ concentration-time curves (P= 0.68) and elimination half-lives (P= 0.39) were similar for the two groups. There was a high frequency (0.179) of the non-wild-type allele of CYP2C8, but no differences between CYP2C8 genotypes with regard to AQ efficacy or safety were evident. The sample size, however, was limited, so monitoring of AQ toxicity in the study area is still indicated. The nonlinear clearance of DEAQ and the wide variability in kinetic parameters have safety implications for weight-based dosing of higher-body-weight children with AQ. The pharmacokinetics of artemisinin combination therapies should be studied in malaria patients, because the rapid parasite clearance caused by the artemisinin may affect the kinetics of the partner drug and the combination.
Cerebrospinal Fluid and Plasma (1→3)-β-d-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental HematogenousCandidaMeningoencephalitis
Authors: Petraitiene Ruta , Petraitis Vidmantas , Hope William W. , Mickiene Diana , Kelaher Amy M. , Murray Heidi A. , Mya-San Christine , Hughes Johanna E. , Cotton Margaret P. , Bacher John , Walsh Thomas J.
Published: September 2008

The treatment, diagnosis and therapeutic monitoring of hematogenousCandidameningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1→3)-β-d-glucan (β-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (102to 103CFU/ml), spinal cord, and meninges (10 to 102CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for β-glucan were positive (755 to 7,750 pg/ml) (P< 0.001). The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg. A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance ofCandida albicansfrom blood cultures was not predictive of eradication of organisms from the CNS; conversely, β-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of β-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P< 0.001). Levels of plasma β-glucan were lower than levels in simultaneously obtained CSF (P< 0.05). CSF β-glucan levels correlated in a dose-dependent pattern with therapeutic responses and withCandidainfection in cerebral tissue (r= 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF β-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME.
Burkholderia thailandensis
as a Model System for the Study of the Virulence-Associated Type III Secretion System of
Burkholderia pseudomallei
Authors: Haraga Andrea , West T. Eoin , Brittnacher Mitchell J. , Skerrett Shawn J. , Miller Samuel I.
Published: September 2008

Burkholderia pseudomallei
is a bacterial pathogen that causes a broad spectrum of clinical symptoms collectively known as melioidosis. Since it can be acquired by inhalation and is difficult to eradicate due to its resistance to a wide group of antibiotics and capacity for latency, work with
B. pseudomallei
requires a biosafety level 3 (BSL-3) containment facility. The
bsa
(
Burkholderia s
ecretion
a
pparatus)-encoded type III secretion system (TTSS) has been shown to be required for its full virulence in a number of animal models. TTSSs are export devices found in a variety of gram-negative bacteria that translocate bacterial effector proteins across host cell membranes into the cytoplasm of host cells. Although the Bsa TTSS has been shown to play an important role in the ability of
B. pseudomallei
to survive and replicate in mammalian cells, escape from the endocytic vacuole, and spread from cell to cell, little is known about its effectors mediating these functions. Using bioinformatics, we identified homologs of several known TTSS effectors from other bacteria in the
B. pseudomallei
genome. In addition, we show that orthologs of these putative effectors exist in the genome of
B. thailandensis
, a closely related bacterium that is rarely pathogenic to humans. By generating a Bsa TTSS mutant
B. thailandensis
strain, we also demonstrated that the Bsa TTSS has similar functions in the two species. Therefore, we propose
B. thailandensis
as a useful BSL-1 model system to study the role of the Bsa TTSS during
Burkholderia
infection of mammalian cells and animals.
Functional Characterization and Novel Rickettsiostatic Effects of a Kunitz-Type Serine Protease Inhibitor from the Tick
Dermacentor variabilis
Authors: Ceraul Shane M. , Dreher-Lesnick Sheila M. , Mulenga Albert , Rahman M. Sayeedur , Azad Abdu F.
Published: September 2008

Here we report the novel bacteriostatic function of a five-domain Kunitz-type serine protease inhibitor (KPI) from the tick
Dermacentor variabilis
. As ticks feed, they release anticoagulants, anti-inflammatory and immunosuppressive molecules that mediate the formation of the feeding lesion on the mammalian host. A number of KPIs have been isolated and characterized from tick salivary gland extracts. Interestingly, we observe little
D. variabilis
KPI gene expression in the salivary gland and abundant expression in the midgut. However, our demonstration of
D. variabilis
KPI's anticoagulant properties indicates that
D. variabilis
KPI may be important for blood meal digestion in the midgut. In addition to facilitating long-term attachment and blood meal acquisition, gene expression studies of
Drosophila
, legumes, and ticks suggest that KPIs play some role in the response to microbial infection. Similarly, in this study, we show that challenge of
D. variabilis
with the spotted fever group rickettsia,
Rickettsia montanensis
, results in sustained
D. variabilis
KPI gene expression in the midgut. Furthermore, our in vitro studies show that
D. variabilis
KPI limits rickettsial colonization of L929 cells (mouse fibroblasts), implicating
D. variabilis
KPI as a bacteriostatic protein, a property that may be related to
D. variabilis
KPI's trypsin inhibitory capability. This work suggests that anticoagulants play some role in the midgut during feeding and that
D. variabilis
KPI may be involved as part of the tick's defense response to rickettsiae.
Comparison of Adhesion and Virulence of Two Predominant Hospital-Acquired Methicillin-Resistant
Staphylococcus aureus
Clones and Clonal Methicillin-Susceptible
S. aureus
Isolates
Authors: Karauzum Hatice , Ferry Tristan , de Bentzmann Sophie , Lina Gérard , Bes Michèle , Vandenesch François , Schmaler Mathias , Berger-Bächi Brigitte , Etienne Jerome , Landmann Regine
Published: September 2008

The virulence of SCC
mec
type IV hospital-acquired methicillin-resistant
Staphylococcus aureus
(MRSA) clinical isolates belonging to the major sequence type 8 (ST8 [Lyon clone]) and to a minor upcoming clone, ST5, was compared with that of methicillin-susceptible
S. aureus
(MSSA) isolates of matching sequence types. In vitro adhesion to human airway epithelial cells (HAECs) as an indicator of dissemination and mortality in a murine sepsis model as an indicator of virulence were evaluated. Ten MRSA isolates and 8 MSSA isolates of ST8 and 8 MRSA isolates and 8 MSSA isolates of ST5 were characterized with respect to multilocus sequence type;
agr, spa
, and capsule typing; in vitro doubling time; toxin and adhesin gene profiles; and adherence to HAECs. Adherence was significantly lower in the MRSA ST5 group than in the ST8 groups. Infections with MRSA and MSSA isolates ST8 and ST5 were compared. No change in virulence related to the presence of SCC
mec
was observed, since ST8 but not ST5 caused a significantly lower mortality in its presence. Despite their similar genetic backgrounds, individual clonal MRSA and MSSA isolates were heterogeneous in adherence and virulence. No one of these specific virulence factors determined in vitro was related to mouse mortality. In conclusion, in a bacteremic model, mortality was dependent on the ST and was differentially modulated by SCC
mec
; within an ST, clonality was not associated with a homogenous outcome.
Creatine supplementation does not affect clinical health markers in football players
Authors: Cancela P , Ohanian C , Cuitiño E , Hackney A C
Published: September 2008

Purpose:

To study the effects of 8-week creatine monohydrate (CrM) supplementation on blood and urinary clinical health markers in football players.

Methods:

14 football players were randomly assigned in a double-blinded fashion to Cre (n = 7) or Pla (n = 7) group. The Cre group ingested 15 g/day of CrM for 7 days and 3 g/day for the remaining 49 days, whereas the Pla group ingested maltodextrin following the same protocol. Football-specific training was performed during the study. Total body mass was determined and blood and urine samples were analysed for metabolic, hepatic, renal and muscular function markers, before and after supplementation.

Results:

A gain of total body mass was observed after CrM intake, but not with placebo. Blood and urinary markers remained within normal reference values. There were no significant changes in renal and hepatic markers after CrM intake. However, total creatine kinase (CK) activity significantly increased, and uric acid level tended to decrease after CrM use. Likewise, serum glucose decreased in the Cre group following supplementation. No significant differences in urine parameters were found in either group after supplementation.

Conclusions:

8 weeks of CrM supplementation had no negative effects on blood and urinary clinical health markers in football players. Properties of CrM may, however, be associated with an increase in CK activity, improving the efficiency for ATP resynthesis, a phenomenon indirectly confirmed by the decreasing tendency in uric acid concentration. Furthermore, CrM seems to slightly influence glucoregulation in trained subjects.
SIGNAL PROCESSING OF MULTICOMPONENT RAMAN SPECTRA OF PARTICULATE MATTER
Authors: FOCHESATTO JAVIER , SLOAN JAMES
Published: September 2008

We report advances in the signal processing of Multicomponent Raman Spectra of particulate matter. We evaluate laboratory and ambient samples collected in field experiments in Canada (during the Pacific 2001 Experiment, Vancouver, BC and at ALERT station, Nunavut, 2002). We discuss methodologies for signal processing the Raman spectra: de-noising and de-peaking, baseline reduction, and identification of chemical fingerprints. The ambient samples were collected near the surface in different environmental conditions during field experiments. In this article we compare and assess the methodologies performances and differences.
SIGNATURE AND SIGNAL GENERATION ASPECTS OF EXPLOSIVE DETECTION USING TERAHERTZ TIME-DOMAIN SPECTROSCOPY
Authors: OSIANDER ROBERT , FITCH MICHAEL J. , LEAHY-HOPPA MEGAN , DIKMELIK YAMAC , SPICER JAMES B.
Published: September 2008

In the last few years, a number of researchers including our collaboration have assembled databases of terahertz (THz) time-domain spectroscopy (TDS) absorption spectra from bulk explosives. While this was a necessary and important step in demonstrating the feasibility of THz TDS for explosives detection, the goal of our research is to demonstrate selectivity of THz spectra from the clutter of background spectra coming from the substrate such as soil or sand. We have investigated THz TDS reflection spectra from sand with different grain sizes as well as from metallic powders in order to distinguish between the signals reflected from the rough surfaces compared to distributed reflections at finite depths in the granular material. With marker materials such as tartaric acid, which have absorption features in the 1-2 THz range, we have investigated the reflection spectra of granular substrates with marker chemicals, and compared this to reflection and transmission spectra of solid materials prepared in polyethylene sample pellets. In principle, the same experiments can then be performed using TNT, RDX, HMX and PETN, which all have characteristic features in the 0.5-8 THz frequency range. Absolute molecular absorption coefficients can be measured as well, and we include here preliminary values for RDX. A full analysis will be reported elsewhere.
SUPPORT VECTOR CLASSIFICATION OF LAND COVER AND BENTHIC HABITAT FROM HYPERSPECTRAL IMAGES
Authors: MANIAN VIDYA , VELEZ-REYES MIGUEL
Published: September 2008

This paper presents a novel wavelet and support vector machine (SVM) based method for hyperspectral image classification. A 1-D wavelet transform is applied to the pixel spectra, followed by feature extraction and SVM classification. Contrary to the traditional method of using pixel spectra with SVM classifier, our approach not only reduces the dimension of the input pixel feature vector but also improves the classification accuracy. Texture energy features computed in the spectral dimension are mapped using polynomial kernels and used for training the SVM classifier. Results with AVIRIS and other hyperspectral images for land cover and benthic habitat classification are presented. The accuracy of the method with limited training sets and computational burden is assessed.
ADVANCED RESPONSIVE TACTICALLY-EFFECTIVE MILITARY IMAGING SPECTROMETER (ARTEMIS) DESIGN
Authors: COOLEY THOMAS W. , LOCKWOOD RONALD B. , DAVIS THOM M. , NADILE RICHARD M. , GARDNER JAMES A. , ARMSTRONG PETER S. , PAYTON ABRAHAM M. , STRAIGHT STANLEY D. , HENRY WAYNE C. , CHRIEN THOMAS G. , GUSSIN EDWARD L. , MAKOWSKI DAVID
Published: September 2008

The Advanced Responsive Tactically-Effective Military Imaging Spectrometer (ARTEMIS) is under development for tactical military applications and is the primary payload for the TacSat-3 satellite. The optical design for the telescope, imaging spectrometer, and high resolution imager is described.
A HIGH-RESOLUTION 2D IMAGING LASER RADAR FOR OCCLUDED HARD TARGET VIEWING AND IDENTIFICATION
Authors: GRASSO ROBERT J. , WIKMAN JOHN C. , DROUIN DAVID P. , DIPPEL GEORGE F. , EGBERT PAUL I.
Published: September 2008

BAE SYSTEMS has developed a Low Cost Targeting System (LCTS) consisting of a FLIR for target detection, laser-illuminated, gated imaging for target identification, laser rangefinder and designator, GPS positioning, and auto-tracking capability within a small compact system size. The system is based upon BAE Systems proven micro-bolometer passive LWIR camera coupled with Intevac's new EBAPS camera. A dual wavelength diode pumped laser provides eyesafe ranging and target illumination, as well as designation; a custom detector module senses the return pulse for target ranging and to set the range gates for the gated camera. Trials show that the current detectors offer complete extinction of signals outside of the gated range, thus, providing high resolution within the gated region. The images have shown high spatial resolution arising from the use of solid state focal plane array technology. Imagery has been collected in both the laboratory and the field to verify system performance during a variety of operating conditions.
THREE DIMENSIONAL FLASH LADAR FOCAL PLANES AND TIME DEPENDENT IMAGING
Authors: STETTNER ROGER , BAILEY HOWARD , SILVERMAN STEVEN
Published: September 2008

3-D flash ladar, herein defined as obtaining an entire frame of 3-D ladar data with one laser pulse, is an emerging technology with a number of advantages over conventional point scanner systems. Probably the most obvious advantage is the higher data rates possible and the potential for much higher data rates with increases in the associated 3-D focal planes array (FPA) format. High data rate means that topographical mapping, for example, can be obtained more rapidly decreasing the amount of flight time required. This paper investigates the clear but perhaps not-so-intuitive use of the high data rate: time dependent 3-D movies can be acquired at the repetition frequency of the associated laser. Data is taken using 3-D flash ladar cameras fabricated by Advanced Scientific Concepts, Inc. The paper concludes that there are a number of advantages and unique applications of the time dynamic 3-D flash ladar, including 3-D collision avoidance and object tracking.
DETECTION OF INVISIBLE BACILLI SPORES ON SURFACES USING A PORTABLE SERS-BASED ANALYZER
Authors: FARQUHARSON STUART , INSCORE FRANK E.
Published: September 2008

Since the distribution of anthrax causing spores through the U.S. Postal System in the autumn of 2001, bioterrorism has become an ever present threat. During and following an attack it is also important to detect spores on surfaces, to assess the extent of an attack, to quantify risk of infection by contact, as well as to evaluate post-attack clean-up. To perform useful measurements, analyzers and/or methods must be capable of detecting as few as 10 spores/cm2, in under 5-minutes, with little or no sample preparation or false-positive responses, using a portable device. In an effort to develop such a device, we have been investigating the ability of surface-enhanced Raman spectroscopy (SERS) to detect dipicolinic acid (DPA) as a chemical signature of bacilli spores. In general, SERS is capable of detecting mg/L concentrations and lower, and providing unequivocal identification of chemicals based on each one's unique spectrum. However, rapid analysis requires extracting the DPA from the spores for SERS detection. Here we describe the use of a room temperature digesting agent in combination with SERS to detect 220 spores on a surface, the entire procedure which was performed in 2.5 minutes.
DETECTION AND IDENTIFICATION OF TOXIC CHEMICAL VAPORS IN AN OPEN-AIR ENVIRONMENT BY A DIFFERENTIAL PASSIVE LWIR STANDOFF TECHNIQUE
Authors: LAVOIE HUGO , PUCKRIN ELDON , THÉRIAULT JEAN-MARC
Published: September 2008

In this paper, the passive standoff long wave infrared technology developed for atmospheric remote sensing was used to detect and identify chemical pollutants in the atmosphere. The measurement approach is based on the differential passive standoff detection method that has been developed by DRDC Valcartier during the past few years. The measurements were performed on real chemical warfare agents and toxic chemical vapors. The results clearly demonstrate the capability of the differential radiometry approach for the detection, identification and quantification of toxic chemical vapor clouds in an open-air environment.