bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of anthropometric patient‐phantom matching on organ dose: A hybrid phantom study for fluoroscopy guided interventions
Authors: Johnson Perry B. , Geyer Amy , Borrego David , Ficarrotta Kayla , Johnson Kevin , Bolch Wesley E.
Published: February 2011

Purpose:

To investigate the benefits and limitations of patient‐phantom matching for determining organ dose during fluoroscopy guided interventions.

Methods:

In this study, 27 CT datasets representing patients of different sizes and genders were contoured and converted into patient‐specific computational models. Each model was matched, based on height and weight, to computational phantoms selected from the UF hybrid patient‐dependent series. In order to investigate the influence of phantom type on patient organ dose, Monte Carlo methods were used to simulate two cardiac projections (PA/left lateral) and two abdominal projections (RAO/LPO). Organ dose conversion coefficients were then calculated for each patient‐specific and patient‐dependent phantom and also for a reference stylized and reference hybrid phantom. The coefficients were subsequently analyzed for any correlation between patient‐specificity and the accuracy of the dose estimate. Accuracy was quantified by calculating an absolute percent difference using the patient‐specific dose conversion coefficients as the reference.

Results:

Patient‐phantom matching was shown most beneficial for estimating the dose to heavy patients. In these cases, the improvement over using a reference stylized phantom ranged from approximately 50% to 120% for abdominal projections and for a reference hybrid phantom from 20% to 60% for all projections. For lighter individuals, patient‐phantom matching was clearly superior to using a reference stylized phantom, but not significantly better than using a reference hybrid phantom for certain fields and projections.

Conclusions:

The results indicate two sources of error when patients are matched with phantoms: Anatomical error, which is inherent due to differences in organ size and location, and error attributed to differences in the total soft tissue attenuation. For small patients, differences in soft tissue attenuation are minimal and are exceeded by inherent anatomical differences. For large patients, difference in soft tissue attenuation can be large. In these cases, patient‐phantom matching proves most effective as differences in soft tissue attenuation are mitigated. With increasing obesity rates, overweight patients will continue to make up a growing fraction of all patients undergoing medical imaging. Thus, having phantoms that better represent this population represents a considerable improvement over previous methods. In response to this study, additional phantoms representing heavier weight percentiles will be added to the UFHADM and UFHADF patient‐dependent series.
Four‐dimensional cone‐beam computed tomography and digital tomosynthesis reconstructions using respiratory signals extracted from transcutaneously inserted metal markers for liver SBRT
Authors: Park Justin C. , Park Sung Ho , Kim Jong Hoon , Yoon Sang Min , Kim Su Ssan , Kim Jin Sung , Liu Zhaowei , Watkins Tyler , Song William Y.
Published: February 2011

Purpose

: Respiration‐induced intrafraction target motion is a concern in liver cancer radiotherapy, especially in stereotactic body radiotherapy (SBRT), and therefore, verification of its motion is necessary. An effective means to localize the liver cancer is to insert metal fiducial markers to or near the tumor with simultaneous imaging using cone‐beam computed tomography (CBCT). Utilizing the fiducial markers, the authors have demonstrated a method to generate breath‐induced motion signal of liver for reconstructing 4D digital tomosynthesis (4DDTS) and 4DCBCT images based on phasewise and/or amplitudewise sorting of projection data.

Methods:

The marker extraction algorithm is based on template matching ofa prior known marker image and has been coded to optimally extract marker positions in CBCT projections from the On‐Board Imager (Varian Medical Systems, Palo Alto, CA). To validate the algorithm, multiple projection images of moving thorax phantom and five patient cases were examined. Upon extraction of the motion signals from the markers, 4D image sorting and image reconstructions were subsequently performed. In the case of incomplete signals due to projections with missing markers, the authors have implemented signal profiling to replace the missing portion.

Results:

The proposed marker extraction algorithm was shown to be very robust and accurate in the phantom and patient cases examined. The maximum discrepancy of the algorithm predicted marker location versus operator selected location was, with the overall average of , for 500 projections. The resulting 4DDTS and 4DCBCT images showed clear reduction in motion‐induced blur of the markers and the anatomy for an effective image guidance. The signal profiling method was useful in replacing missing signals.

Conclusions:

The authors have successfully demonstrated that motion tracking of fiducial markers and the subsequent 4D reconstruction of CBCT and DTS are possible. Due to the significant reduction in motion‐induced image blur, it is anticipated that such technology will be useful in image‐guided liver SBRT treatments.
Performance measurements for the PET/CT Discovery‐600 using NEMA NU 2‐2007 standards
Authors: De Ponti E. , Morzenti S. , Guerra L. , Pasquali C. , Arosio M. , Bettinardi V. , Crespi A. , Gilardi M. C. , Messa C.
Published: February 2011

Purpose:

The aim of this study was to assess the performance measurements of the new PET/CT system Discovery‐600 (D‐600, GEMS, Milwaukee, WI).

Methods:

Performance measures were obtained with the National Electrical Manufacturers Association (NEMA) NU 2‐2007 procedures.

Results:

The transverse (axial) spatial resolution FWHMs were 4.9 (5.6) mm and 5.6 (6.4) mm at 1 and 10 cm off axis, respectively. The sensitivity (average at 0 and 10 cm) was 9.6 cps/kBq. The scatter fraction was 36.6% (low energy threshold: 425 keV). The NEC peak rate was 75.2 kcps at 12.9 kBq/cc. The hot contrasts for 10, 13, 17, and 22 mm spheres were 41%, 51%, 62%, and 73% and the cold contrasts for 28 and 37 mm spheres were 68% and 72%.

Conclusions:

The Discovery‐600 has good performance for the NEMA NU 2‐2007 parameters, particularly in improved sensitivity compared to the scanners of the same Discovery family, D‐ST and D‐STE.
Assessing risk of baleen whale hearing loss from seismic surveys: The effect of uncertainty and individual variation
Authors: Gedamke Jason , Gales Nick , Frydman Sascha
Published: February 2011

The potential for seismic airgun “shots” to cause acoustic trauma in marine mammals is poorly understood. There are just two empirical measurements of temporary threshold shift (TTS) onset levels from airgun-like sounds in odontocetes. Considering these limited data, a model was developed examining the impact of individual variability and uncertainty on risk assessment of baleen whale TTS from seismic surveys. In each of 100 simulations: 10000 “whales” are assigned TTS onset levels accounting for: inter-individual variation; uncertainty over the population’s mean; and uncertainty over weighting of odontocete data to obtain baleen whale onset levels. Randomly distributed whales are exposed to one seismic survey passage with cumulative exposure level calculated. In the base scenario, 29% of whales (5th/95th percentiles of 10%/62%) approached to 1–1.2 km range were exposed to levels sufficient for TTS onset. By comparison, no whales are at risk outside 0.6 km when uncertainty and variability are not considered. Potentially “exposure altering” parameters (movement, avoidance, surfacing, and effective quiet) were also simulated. Until more research refines model inputs, the results suggest a reasonable likelihood that whales at a kilometer or more from seismic surveys could potentially be susceptible to TTS and demonstrate the large impact uncertainty and variability can have on risk assessment.
Perceiving unstressed vowels in foreign-accented English
Authors: Braun Bettina , Lemhöfer Kristin , Mani Nivedita
Published: February 2011

This paper investigated how foreign-accented stress cues affect on-line speech comprehension in British speakers of English. While unstressed English vowels are usually reduced to /ə/, Dutch speakers of English only slightly centralize them. Speakers of both languages differentiate stress by suprasegmentals (duration and intensity). In a cross-modal priming experiment, English listeners heard sentences ending in monosyllabic prime fragments—produced by either an English or a Dutch speaker of English—and performed lexical decisions on visual targets. Primes were either stress-matching (“ab” excised from absurd), stress-mismatching (“ab” from absence), or unrelated (“pro” from profound) with respect to the target (e.g., ABSURD). Results showed a priming effect for stress-matching primes only when produced by the English speaker, suggesting that vowel quality is a more important cue to word stress than suprasegmental information. Furthermore, for visual targets with word-initial secondary stress that do not require vowel reduction (e.g., CAMPAIGN), resembling the Dutch way of realizing stress, there was a priming effect for both speakers. Hence, our data suggest that Dutch-accented English is not harder to understand in general, but it is in instances where the language-specific implementation of lexical stress differs across languages.
Aspects of ground effect modeling
Authors: Taraldsen Gunnar , Jonasson Hans
Published: February 2011

A recently published one-parameter ground model based on Darcy’s law is here generalized into a two-parameter model which depends on an effective flow resistivity and an effective layer depth. Extensive field measurements of the acoustic impedance of various ground types have been carried out for frequencies in the range from 200 Hz to 2.5 kHz. The model based on Darcy’s law gives an improved fit to the measurements compared to the Delany–Bazley model. It is, in addition, argued on purely theoretical grounds that the suggested model is preferable. In contrast to the Delany–Bazley model it corresponds to a proper causal time-domain model. This is particularly relevant for extrapolation of the models to lower frequencies and for the recently developed harmonized methods intended for use in the implementation of the European Union directive on the assessment and management of environmental noise. The harmonized methods include frequencies down to the 25 Hz third octave band and have the Delany–Bazley ground impedance model as the default choice. The arguments presented here suggest that this default choice should be replaced by the more physically based model from the law of Darcy.
Evaluation of a wave-vector-frequency-domain method for nonlinear wave propagation
Authors: Jing Yun , Tao Molei , Clement Greg T.
Published: February 2011

A wave-vector-frequency-domain method is presented to describe one-directional forward or backward acoustic wave propagation in a nonlinear homogeneous medium. Starting from a frequency-domain representation of the second-order nonlinear acoustic wave equation, an implicit solution for the nonlinear term is proposed by employing the Green’s function. Its approximation, which is more suitable for numerical implementation, is used. An error study is carried out to test the efficiency of the model by comparing the results with the Fubini solution. It is shown that the error grows as the propagation distance and step-size increase. However, for the specific case tested, even at a step size as large as one wavelength, sufficient accuracy for plane-wave propagation is observed. A two-dimensional steered transducer problem is explored to verify the nonlinear acoustic field directional independence of the model. A three-dimensional single-element transducer problem is solved to verify the forward model by comparing it with an existing nonlinear wave propagation code. Finally, backward-projection behavior is examined. The sound field over a plane in an absorptive medium is backward projected to the source and compared with the initial field, where good agreement is observed.
Multiple scattering of ultrasound in weakly inhomogeneous media: Application to human soft tissues
Authors: Aubry Alexandre , Derode Arnaud
Published: February 2011

Waves scattered by a weakly inhomogeneous random medium contain a predominant single-scattering contribution as well as a multiple-scattering contribution which is usually neglected, especially for imaging purposes. A method based on random matrix theory is proposed to separate the single- and multiple-scattering contributions. The experimental setup uses an array of sources/receivers placed in front of the medium. The impulse responses between every couple of transducers are measured and form a matrix. Single-scattering contributions are shown to exhibit a deterministic coherence along the antidiagonals of the array response matrix, whatever the distribution of inhomogeneities. This property is taken advantage of to discriminate single- from multiple-scattered waves. This allows one to evaluate the absorption losses and the scattering losses separately, by comparing the multiple-scattering intensity with a radiative transfer model. Moreover, the relative contribution of multiple scattering in the backscattered wave can be estimated, which serves as a validity test for the Born approximation. Experimental results are presented with ultrasonic waves in the megahertz range, on a synthetic sample (agar–gelatine gel) as well as on breast tissues. Interestingly, the multiple-scattering contribution is found to be far from negligible in the breast around 4.3 MHz.
Target detection and localization in shallow water: An experimental demonstration of the acoustic barrier problem at the laboratory scale
Authors: Marandet Christian , Roux Philippe , Nicolas Barbara , Mars Jérôme
Published: February 2011

This study demonstrates experimentally at the laboratory scale the detection and localization of a wavelength-sized target in a shallow ultrasonic waveguide between two source–receiver arrays at 3 MHz. In the framework of the acoustic barrier problem, at the 1/1000 scale, the waveguide represents a 1.1-km-long, 52-m-deep ocean acoustic channel in the kilohertz frequency range. The two coplanar arrays record in the time-domain the transfer matrix of the waveguide between each pair of source–receiver transducers. Invoking the reciprocity principle, a time-domain double-beamforming algorithm is simultaneously performed on the source and receiver arrays. This array processing projects the multireverberated acoustic echoes into an equivalent set of eigenrays, which are defined by their launch and arrival angles. Comparison is made between the intensity of each eigenray without and with a target for detection in the waveguide. Localization is performed through tomography inversion of the acoustic impedance of the target, using all of the eigenrays extracted from double beamforming. The use of the diffraction-based sensitivity kernel for each eigenray provides both the localization and the signature of the target. Experimental results are shown in the presence of surface waves, and methodological issues are discussed for detection and localization.
Effect of speech-intrinsic variations on human and automatic recognition of spoken phonemes
Authors: Meyer Bernd T. , Brand Thomas , Kollmeier Birger
Published: February 2011

The aim of this study is to quantify the gap between the recognition performance of human listeners and an automatic speech recognition (ASR) system with special focus on intrinsic variations of speech, such as speaking rate and effort, altered pitch, and the presence of dialect and accent. Second, it is investigated if the most common ASR features contain all information required to recognize speech in noisy environments by using resynthesized ASR features in listening experiments. For the phoneme recognition task, the ASR system achieved the human performance level only when the signal-to-noise ratio (SNR) was increased by 15 dB, which is an estimate for the human–machine gap in terms of the SNR. The major part of this gap is attributed to the feature extraction stage, since human listeners achieve comparable recognition scores when the SNR difference between unaltered and resynthesized utterances is 10 dB. Intrinsic variabilities result in strong increases of error rates, both in human speech recognition (HSR) and ASR (with a relative increase of up to 120%). An analysis of phoneme duration and recognition rates indicates that human listeners are better able to identify temporal cues than the machine at low SNRs, which suggests incorporating information about the temporal dynamics of speech into ASR systems.
Aircraft noise: Accounting for changes in air traffic with time of day
Authors: Schäffer Beat , Bütikofer Rudolf , Plüss Stefan , Thomann Georg
Published: February 2011

Aircraft noise contours are estimated using model calculations and, due to their impact on land use planning, they need to be highly accurate. During night time, not only the number and dominant types of aircraft may differ from daytime but also the flight paths flown may differ. To determine to which detail these variations in flight paths need to be considered, calculations were performed exemplarily for two airports using all available radar data over 1 year, taking into account their changes over the day. The results of this approach were compared with results of a simpler approach which does not consider such changes. While both calculations yielded similar results for the day and close to the airport, differences increased with distance as well as with the period of day (day < first hour of the night < second hour of the night, respectively, day < evening < night). Only the detailed calculation always accounted for the flight path changes in full detail. Possible legal consequences of such different modeling approaches are estimated, and the model results are compared to monitoring measurements. Finally, the situations for which the simpler approach is sufficiently accurate are ascertained.
Frequency discrimination duration effects for Huggins pitch and narrowband noise (L)
Authors: Plack Christopher J. , Turgeon Martine , Lancaster Stuart , Carlyon Robert P. , Gockel Hedwig E.
Published: February 2011

Frequency difference limens (FDLs) were measured for Huggins pitch (HP) stimuli, consisting of a 30-Hz wide band of interaurally decorrelated noise in a diotic low-pass noise and for 30-Hz wide bands of diotic narrowband noise presented in a diotic low-pass noise background. FDLs at a 400-ms duration for the two stimulus types were equated by adjusting the level of the narrowband noise relative to the background. The effects of duration on the FDLs were then measured for center frequencies of 300, 600, and 900 Hz. Although the results were compromised by floor effects at 900 Hz, at 300 and 600 Hz, the duration effects were very similar for the HP and narrowband noise stimuli, with a large improvement in performance between 100 and 400 ms. In contrast to previous results for pure tones, the effect of duration was independent of frequency. The results suggest that: (1) Binaural and monaural pitches may be processed using a common mechanism; (2) discrimination performance for HP and low-sensation-level narrowband noise stimuli is not determined by the number of waveform periods.
Trumpet with near-perfect harmonicity: Design and acoustic results
Authors: Macaluso Charles A. , Dalmont Jean-Pierre
Published: February 2011

This paper presents a mathematical design methodology for determining the shape of a trumpet air column that has near-perfect harmonicity, whose components are discontinuity-free, and whose input impedance peak heights are balanced over the playing range. The simulation model employed assumes linear wave propagation and uses cylindrical element discretization with a plane wave approximation. Acoustic measurements are made using a test set-up with an estimated relative measurement error of ±3 cents. Comparisons of measured results are given for the presented design (Macaluso trumpet) and the same trumpet air column with the bell replaced by a commercially used generic trumpet bell of unknown shape (Generic trumpet). For acoustic resonance modes 2–13 (233–1515 Hz), the measured root-mean-square (rms) harmonicity deviation is 5 cents for the Macaluso trumpet, whereas it is 18 cents for the Generic trumpet. However, considering the estimated measurement uncertainty, each of those deviations is somewhat over-stated. For that same range of resonances, the rms deviation between measured and calculated resonance frequencies for the Macaluso trumpet is 3 cents, thus validating the presented simulation model and equations.
Harmonic source wavefront aberration correction for ultrasound imaging
Authors: Dianis Scott W. , von Ramm Olaf T.
Published: February 2011

A method is proposed which uses a lower-frequency transmit to create a known harmonic acoustical source in tissue suitable for wavefront correction without a priori assumptions of the target or requiring a transponder. The measurement and imaging steps of this method were implemented on the Duke phased array system with a two-dimensional (2-D) array. The method was tested with multiple electronic aberrators [0.39π to 1.16π radians root-mean-square (rms) at 4.17 MHz] and with a physical aberrator 0.17π radians rms at 4.17 MHz) in a variety of imaging situations. Corrections were quantified in terms of peak beam amplitude compared to the unaberrated case, with restoration between 0.6 and 36.6 dB of peak amplitude with a single correction. Standard phantom images before and after correction were obtained and showed both visible improvement and 14 dB contrast improvement after correction. This method, when combined with previous phase correction methods, may be an important step that leads to improved clinical images.
Acoustical power amplification and damping by temperature gradients
Authors: Biwa Tetsushi , Komatsu Ryo , Yazaki Taichi
Published: February 2011

Ceperley proposed a concept of a traveling wave heat engine [“A pistonless Stirling engine—The traveling wave heat engine,” J. Acoust. Soc. Am. 66, 1508–1513 (1979).] that provided a starting point of thermoacoustics today. This paper verifies experimentally his idea through observation of amplification and strong damping of a plane acoustic traveling wave as it passes through axial temperature gradients. The acoustic power gain is shown to obey a universal curve specified by a dimensionless parameter ωτα; ω is the angular frequency and τα is the relaxation time for the gas to thermally equilibrate with channel walls. As an application of his idea, a three-stage acoustic power amplifier is developed, which attains the gain up to 10 with a moderate temperature ratio of 2.3.
Near-threshold equal-loudness contours for harbor seals (Phoca vitulina) derived from reaction times during underwater audiometry: A preliminary study
Authors: Kastelein Ronald A. , Wensveen Paul J. , Terhune John M. , de Jong Christ A. F.
Published: February 2011

Equal-loudness functions describe relationships between the frequencies of sounds and their perceived loudness. This pilot study investigated the possibility of deriving equal-loudness contours based on the assumption that sounds of equal perceived loudness elicit equal reaction times (RTs). During a psychoacoustic underwater hearing study, the responses of two young female harbor seals to tonal signals between 0.125 and 100 kHz were filmed. Frame-by-frame analysis was used to quantify RT (the time between the onset of the sound stimulus and the onset of movement of the seal away from the listening station). Near-threshold equal-latency contours, as surrogates for equal-loudness contours, were estimated from RT-level functions fitted to mean RT data. The closer the received sound pressure level was to the 50% detection hearing threshold, the more slowly the animals reacted to the signal (RT range: 188–982 ms). Equal-latency contours were calculated relative to the RTs shown by each seal at sound levels of 0, 10, and 20 dB above the detection threshold at 1 kHz. Fifty percent detection thresholds are obtained with well-trained subjects actively listening for faint familiar sounds. When calculating audibility ranges of sounds for harbor seals in nature, it may be appropriate to consider levels 20 dB above this threshold.
Echolocation call intensity and directionality in flying short-tailed fruit bats, Carollia perspicillata (Phyllostomidae)
Authors: Brinkløv Signe , Jakobsen Lasse , Ratcliffe John M. , Kalko Elisabeth K. V. , Surlykke Annemarie
Published: February 2011

The directionality of bat echolocation calls defines the width of bats’ sonar “view,” while call intensity directly influences detection range since adequate sound energy must impinge upon objects to return audible echoes. Both are thus crucial parameters for understanding biosonar signal design. Phyllostomid bats have been classified as low intensity or “whispering bats,” but recent data indicate that this designation may be inaccurate. Echolocation beam directionality in phyllostomids has only been measured through electrode brain-stimulation of restrained bats, presumably excluding active beam control via the noseleaf. Here, a 12-microphone array was used to measure echolocation call intensity and beam directionality in the frugivorous phyllostomid, Carollia perspicillata, echolocating in flight. The results showed a considerably narrower beam shape (half-amplitude beam angles of approximately 16° horizontally and 14° vertically) and louder echolocation calls [source levels averaging 99 dB sound pressure level (SPL) root mean square] for C. perspicillata than was found for this species when stationary. This suggests that naturally behaving phyllostomids shape their sound beam to achieve a longer and narrower sonar range than previously thought. C. perspicillata orient and forage in the forest interior and the narrow beam might be adaptive in clutter, by reducing the number and intensity of off-axis echoes.
Trouble-shooting deployment and recovery options for various stationary passive acoustic monitoring devices in both shallow- and deep-water applications
Authors: Dudzinski Kathleen M. , Brown Shani J. , Lammers Marc , Lucke Klaus , Mann David A. , Simard Peter , Wall Carrie C. , Rasmussen Marianne Helene , Magnúsdóttir Edda Elísabet , Tougaard Jakob , Eriksen Nina
Published: February 2011

Deployment of any type of measuring device into the ocean, whether to shallow or deeper depths, is accompanied by the hope that this equipment and associated data will be recovered. The ocean is harsh on gear. Salt water corrodes. Currents, tides, surge, storms, and winds collaborate to increase the severity of the conditions that monitoring devices will endure. All ocean-related research has encountered the situations described in this paper. In collating the details of various deployment and recovery scenarios related to stationary passive acoustic monitoring use in the ocean, it is the intent of this paper to share trouble-shooting successes and failures to guide future work with this gear to monitor marine mammal, fish, and ambient (biologic and anthropogenic) sounds in the ocean—in both coastal and open waters.
Echolocation signals of Heaviside’s dolphins (Cephalorhynchus heavisidii)
Authors: Morisaka Tadamichi , Karczmarski Leszek , Akamatsu Tomonari , Sakai Mai , Dawson Steve , Thornton Meredith
Published: February 2011

Field recordings of echolocation signals produced by Heaviside’s dolphins (Cephalorhynchus heavisidii) were made off the coast of South Africa using a hydrophone array system. The system consisted of three hydrophones and an A-tag (miniature stereo acoustic data-logger). The mean centroid frequency was 125 kHz, with a −3 dB bandwidth of 15 kHz and −10 dB duration of 74 μs. The mean back-calculated apparent source level was 173 dB re 1 μPap.-p.. These characteristics are very similar to those found in other Cephalorhynchus species, and such narrow-band high-frequency echolocation clicks appear to be a defining characteristic of the Cephalorhynchus genus. Click bursts with very short inter-click intervals (up to 2 ms) were also recorded, which produced the “cry” sound reported in other Cephalorhynchus species. Since inter-click intervals correlated positively to click duration and negatively to bandwidth, Heaviside’s dolphins may adjust their click duration and bandwidth based on detection range. The bimodal distribution of the peak frequency and stable bimodal peaks in spectra of individual click suggest a slight asymmetry in the click production mechanism.
Experimental implementation of reverse time migration for nondestructive evaluation applications
Authors: Anderson Brian E. , Griffa Michele , Bas Pierre-Yves Le , Ulrich Timothy J. , Johnson Paul A.
Published: February 2011

Reverse time migration (RTM) is a commonly employed imaging technique in seismic applications (e.g., to image reservoirs of oil). Its standard implementation cannot account for multiple scattering/reverberation. For this reason it has not yet found application in nondestructive evaluation (NDE). This paper applies RTM imaging to NDE applications in bounded samples, where reverberation is always present. This paper presents a fully experimental implementation of RTM, whereas in seismic applications, only part of the procedure is done experimentally. A modified RTM imaging condition is able to localize scatterers and locations of disbonding. Experiments are conducted on aluminum samples with controlled scatterers.
Lateralization produced by interaural intensitive disparities appears to be larger for high- vs low-frequency stimuli
Authors: Bernstein Leslie R. , Trahiotis Constantine
Published: February 2011

The purpose of this communication is to report the results of a study indicating that a given magnitude of interaural intensitive disparity (IID) produced a larger extent of laterality, as measured via an acoustic pointer, for stimuli centered at 4 kHz than for stimuli centered at 500 Hz. The data and their analysis, taken together, suggest that the findings reflect true across-frequency differences rather than being manifestations of response-related factors.
Noise tolerance in human frequency-following responses to voice pitch
Authors: Li Ximing , Jeng Fuh-Cherng
Published: February 2011

Speech communication usually occurs in the presence of background noise. This study examined noise tolerance in the brainstem’s processing of voice pitch, as reflected by the scalp-recorded frequency-following response (FFR) from 12 normal-hearing adults. By systematically manipulating signal-to-noise ratio (SNR) across three different stimulus intensities, the results indicated that Frequency Error, Slope Error, and Tracking Accuracy remained relatively stable until SNR was degraded to 0 dB or lower (i.e., a turning point). This turning point not only provided physiological evidence supporting pitch tolerance of noise but also allowed recommendation of a minimal SNR when evaluating pitch processing in difficult-to-test patients.
Humanizing Animal Models: A Key to Autoimmune Diabetes Treatment
Authors: Bresson Damien , von Herrath Matthias
Published: February 2011

A new humanized mouse model can be used to predict the clinical behavior of therapeutic antibodies for the treatment of Type 1 diabetes.
Going With the Flow
Authors: Ng Kenneth W.
Published: February 2011

Prolonged growth factor delivery using a hydrogel improves blood vessel formation in the heart.
Adiponectin Battles Ceramides
Authors: Buettner Christoph
Published: February 2011

The beneficial effects of adiponectin are mediated through the ceramidase activity of its receptor.
A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm
Authors: Aderem Alan , Adkins Joshua N. , Ansong Charles , Galagan James , Kaiser Shari , Korth Marcus J. , Law G. Lynn , McDermott Jason G. , Proll Sean C. , Rosenberger Carrie , Schoolnik Gary , Katze Michael G.
Published: February 2011

The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm.
Tectonic style and structural analysis of the Puebla de Guzmán Antiform (Iberian Pyrite Belt, South Portuguese Zone, SW Spain)
Authors: Mantero Elena M. , Alonso-Chaves Francisco M. , García-Navarro Encarnación , Azor Antonio
Published: February 2011

In the South Portuguese Zone (Iberian Massif), thin-skinned tectonics linked to the collision with the Ossa-Morena Zone produced the inversion of previous extensional basins in Carboniferous times. Its central domain, namely the Iberian Pyrite Belt, underwent two deformation phases at mostly low-grade metamorphic conditions linked to a progressive deformation migrating upwards from a basal detachment and from north to south. The Puebla de Guzmán Antiform is one of the most outstanding cartographic structures in the Iberian Pyrite Belt, representing a imbricate fan thrust system developed during the second regional deformation phase. In the Puebla de Guzmán Antiform, the first deformation phase gave rise to a penetrative slaty cleavage (S
1
), which is also recognized in the whole Iberian Pyrite Belt and constitutes the main foliation all over the region. Its genesis is possibly linked to the coetaneous development of thrusts at deeper crustal levels and SSW-vergent folds at all levels above these thrusts. First phase structures were deformed by large-scale imbricated thrust systems with lateral (NNE–SSW) and frontal (WNW–ESE) ramps, which constitute the most relevant regional cartographic structures. This second deformation phase generated thrusts, two set of folds with WNW–ESE and NNE–SSW-oriented axes, as well as two related axial plane crenulation cleavages. These relatively brittle to ductile-brittle second phase structures have been identified in many areas of the Iberian Pyrite Belt, and especially in the southern limb of the Puebla de Guzmán Antiform. The second phase thrusts reported from the Puebla de Guzmán Antiform have not been folded according to both the geological map of the area and the analysis of maximum shortening and stretching axes.
Incremental slip history of a thrust: diverse transport directions and internal folding of the Utrillas thrust sheet (NE Iberian Chain, Spain)
Authors: Simón J. L. , Liesa C. L.
Published: February 2011

A kinematical model for the Utrillas thrust is proposed, including reconstruction of the incremental slip history, progressive internal deformation and tectono-sedimentary relationships at the Montalbán (foreland) and Aliaga (piggy-back) Tertiary basins. A 3D geometrical model of the main thrust surface, defined by ramps oriented NE–SW, east–west, NW–SE and north–south, is reconstructed from cross-sections. Besides, the thrust sheet is internally deformed by two main, frequently superposed fold sets, trending NW–SE to NNW–SSE (earlier) and east–west (later), respectively. A total ‘arrow’ (finite horizontal displacement) of about 5.9 km towards N032°E is estimated by means of schematic, plan-view retrodeformation of the distinctly oriented ramps making its front. Orientation and cross-cut relationships of mesoscopic kinematical indicators at the thrust front provide a scenario of successive transport directions towards the ENE, NNE and north, which is consistent with the progressive development of internal folding, as well as with the evolution of intraplate compressive stress fields through Tertiary times.
Role of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats
Authors: Guo Qiao-Yan , Miao Li-Ning , Li Bing , Ma Fu-Zhe , Liu Nian , Cai Lu , Xu Zhong-Gao
Published: February 2011

12-lipoxygenase (12-LO) was implicated in the development of diabetic nephropathy (DN), in which the proteinuria was thought to be associated with a decreased expression of glomerular P-cadherin. Therefore, we investigated the role of 12-LO in the glomerular P-cadherin expression in type 2 diabetic rats according to the glomerular sizes. Rats fed with high-fat diet for 6 wk were treated with low-dose streptozotocin. Once diabetes onset, diabetic rats were treated with 12-LO inhibitor cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC) for 8 wk. Then glomeruli were isolated from diabetic and control rats with a sieving method. RT-PCR, Western blotting, and immunofluorescent staining were used for mRNA and protein expressions of P-cadherin and angiotensin II (Ang II) type 1 receptor (AT1). We found that CDC did not affect the glucose levels but completely attenuated diabetic increases in glomerular volume and proteinuria. Diabetes significantly decreased the P-cadherin mRNA and protein expressions and increased the AT1 mRNA and protein expressions in the glomeruli. These changes were significantly prevented by CDC and recaptured by direct infusion of 12-LO product [12(S)-HETE] to normal rats for 7 days. The decreased P-cadherin expression was similar between large and small glomeruli, but the increased AT1 expression was significantly higher in the large than in the small glomeruli from diabetic and 12(S)-HETE-treated rats. Direct infusion of normal rats with Ang II for 14 days also significantly decreased the glomerular P-cadherin expression. These results suggest that diabetic proteinuria is mediated by the activation of 12-LO pathway that is partially attributed to the decreased glomerular P-cadherin expression.
The effects of physiological adaptations to calorie restriction on global cell proliferation rates
Authors: Bruss Matthew D. , Thompson Airlia C. S. , Aggarwal Ishita , Khambatta Cyrus F. , Hellerstein Marc K.
Published: February 2011

Calorie restriction (CR) reduces the rate of cell proliferation in mitotic tissues. It has been suggested that this reduction in cell proliferation may mediate CR-induced increases in longevity. However, the mechanisms that lead to CR-induced reductions in cell proliferation rates remain unclear. To evaluate the CR-induced physiological adaptations that may mediate reductions in cell proliferation rates, we altered housing temperature and access to voluntary running wheels to determine the effects of food intake, energy expenditure, percent body fat, and body weight on proliferation rates of keratinocytes, liver cells, mammary epithelial cells, and splenic T-cells in C57BL/6 mice. We found that ∼20% CR led to a reduction in cell proliferation rates in all cell types. However, lower cell proliferation rates were not observed with reductions in 1) food intake and energy expenditure in female mice housed at 27°C, 2) percent body fat in female mice provided running wheels, or 3) body weight in male mice provided running wheels compared with ad libitum-fed controls. In contrast, reductions in insulin-like growth factor I were associated with decreased cell proliferation rates. Taken together, these data suggest that CR-induced reductions in food intake, energy expenditure, percent body fat, and body weight do not account for the reductions in global cell proliferation rates observed in CR. In addition, these data are consistent with the hypothesis that reduced cell proliferation rates could be useful as a biomarker of interventions that increase longevity.
DCAMKL-1 Regulates Epithelial–Mesenchymal Transition in Human Pancreatic Cells through a miR-200a–Dependent Mechanism
Authors: Sureban Sripathi M. , May Randal , Lightfoot Stan A. , Hoskins Aimee B. , Lerner Megan , Brackett Daniel J. , Postier Russell G. , Ramanujam Rama , Mohammed Altaf , Rao Chinthalapally V. , Wyche James H. , Anant Shrikant , Houchen Courtney W.
Published: February 2011

Pancreatic cancer is an exceptionally aggressive disease in great need of more effective therapeutic options. Epithelial–mesenchymal transition (EMT) plays a key role in cancer invasion and metastasis, and there is a gain of stem cell properties during EMT. Here we report increased expression of the putative pancreatic stem cell marker DCAMKL-1 in an established KRAS transgenic mouse model of pancreatic cancer and in human pancreatic adenocarcinoma. Colocalization of DCAMKL-1 with vimentin, a marker of mesenchymal lineage, along with 14-3-3 σ was observed within premalignant PanIN lesions that arise in the mouse model. siRNA-mediated knockdown of DCAMKL-1 in human pancreatic cancer cells induced microRNA miR-200a, an EMT inhibitor, along with downregulation of EMT-associated transcription factors ZEB1, ZEB2, Snail, Slug, and Twist. Furthermore, DCAMKL-1 knockdown resulted in downregulation of c-Myc and KRAS through a let-7a microRNA-dependent mechanism, and downregulation of Notch-1 through a miR-144 microRNA-dependent mechanism. These findings illustrate direct regulatory links between DCAMKL-1, microRNAs, and EMT in pancreatic cancer. Moreover, they demonstrate a functional role for DCAMKL-1 in pancreatic cancer. Together, our results rationalize DCAMKL-1 as a therapeutic target for eradicating pancreatic cancers. Cancer Res; 71(6); 2328–38. ©2011 AACR.
Small Molecule Inhibitors Targeting the “Achilles' Heel” of Androgen Receptor Activity
Authors: Sadar Marianne D.
Published: February 2011

Androgen ablation therapy remains the gold standard for the treatment of advanced prostate cancer, but unfortunately, it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer (CRPC). Mounting evidence supports the concept that development of CRPC is causally related to continued transactivation of androgen receptor (AR). All current therapies that target the AR are dependent on the presence of its C-terminal ligand-binding domain (LBD). However, it is the N-terminal domain (NTD) of the AR that is the “Achilles' heel” of AR activity, with AF-1 being essential for AR activity regardless of androgen. Recent efforts to develop drugs to the AR NTD have yielded EPI-001, a small molecule, sintokamide peptides, and decoys to the AR NTD with EPI-001, the best characterized and most promising for clinical development based upon specificity, low toxicity, and cytoreductive antitumor activity. Cancer Res; 71(4); 1208–13. ©2011 AACR.
Cancer Therapy Associated Bone Loss: Implications for Hip Fractures in Mid-Life Women with Breast Cancer
Authors: Edwards Beatrice J. , Raisch Dennis W. , Shankaran Veena , McKoy June M. , Gradishar William , Bunta Andrew D. , Samaras Athena T. , Boyle Simone N. , Bennett Charles L. , West Dennis P. , Guise Theresa A.
Published: February 2011

Purpose: Aromatase inhibitors (AIs) have been recently associated with hip fractures. We present a case series of breast cancer survivors and a systematic review of bone health care in breast cancer.

Experimental Design: We completed clinical assessments and bone density testing (BMD) of hip fractures from January 2005 to December 2008. Prefracture and 12-month functional status was obtained. Systematic review included case reports and review of MEDLINE, PubMed, EMBASE, and Food and Drug Administration Adverse Event Reporting System (FDA AERS) from January 1998 to December 2008 (search terms: breast cancer, bone loss, osteopenia, osteoporosis, malignancy, cancer treatment, menopause, adriamycin, cytoxan, tamoxifen, and AIs).

Results: Median age was 53.5 years; five women had osteopenia, one osteoporosis. Five cases were ER (+), and received surgery, XRT chemotherapy, and anastrozole. Functional decline was noted at 12 months, with difficulty in performing heavy housekeeping, climbing stairs, and shopping. The FDA AERS database included 228 cases of fractures associated with breast cancer therapy; 77/228 (29.4%) were hip or femur fractures. Among mid-life women under the age of 64 years there were 78 fractures; 15/228 (19%) were hip and femur fractures. AIs were the most common drug class associated with fractures (n = 149, 65%).

Conclusions: Cancer treatment induced bone loss results in hip fractures among mid-life women with breast cancer. Hip fractures occur at younger ages and higher BMD than expected for patients in this age group without breast cancer. Hip fractures result in considerable functional decline. Greater awareness of this adverse drug effect is needed. Clin Cancer Res; 17(3); 560–8. ©2011 AACR.
Gastric Atrophy and Intestinal Metaplasia before and after Helicobacter pylori Eradication: A Meta-Analysis
Authors: Wang Jin , Xu Lijuan , Shi Ruihua , Huang Xiayue , Li Simon Wing Heng , Huang Zuhu , Zhang Guoxin
Published: January 2011

Objective: Whether gastric atrophy (GA) and intestinal metaplasia (IM) are reversible after the eradication of Helicobacter pylori remains controversial. The purpose of this meta-analysis was to systematically review histological alterations in GA and IM by comparing histological scores before and after H. pylori eradication. Methods: English-language articles in the medical literature containing information about the association between infection with H. pylori and gastric premalignant lesions (i.e. GA and IM) were identified by searching the Medline, PubMed, and EMBASE databases with suitable key words up to December 2009. Review Manager 4.2.8 was used for the meta-analysis. Results: Twelve studies containing a total of 2,658 patients were included in the first meta-analysis. Before treatment, 2,648 patients had antrum GA, 2,401 patients had corpus GA, 2,582 patients had antrum IM, and 2,460 patients had corpus IM. Comparing the histological alterations before and after H. pylori eradication, the pooled weighted mean difference (WMD) with 95% CI for antral GA was 0.12 (0.00–0.23), p = 0.06. For corpus GA, the pooled WMD was 0.32 (0.09–0.54), p = 0.006. For antral IM, the pooled WMD was 0.02 (–0.12–0.16), p = 0.76, and for corpus IM, the pooled WMD was –0.02 (–0.05–0.02), p = 0.42. Conclusion: Our study shows that eradication of H. pylori results in significant improvement in GA in the corpus but not in the antrum; it also does not improve gastric mucous IM. Consequently, all patients with GA in the corpus should be tested for H. pylori infection, and eradication therapy should be prescribed for H. pylori-positive patients in those with GA in corpus.