bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel strategy to increase heating efficiency in a split‐focus ultrasound phased array
Authors: Liu Hao‐Li , Shih Tzu‐Ching , Chen Wen‐Shiang , Ju Kuen‐Cheng
Published: July 2007

Focus splitting using sector‐based phased arrays increases the necrosed volume in a single sonication and reduces the total treatment time in the treatment of large tumors. However, split‐focus sonication results in a lower energy density and worse focal‐beam distortion, which limits its usefulness in practical treatments. Here, we propose a new heating strategy involving consecutive strongly focused and split‐focus sonications to improve the heating efficiency. Theoretical predictions including linear and thermal‐dose‐dependent attenuation change were employed to investigate potential factors of this strategy, and ex vivo tissue experiments were conducted to confirm its effectiveness. Results showed that the thermal lesions produced by the proposed strategy could be increased when comparing with the previous reported strategies. The proposed heating strategy also induces a thermal lesion more rapidly, and exhibits higher robustness to various blood perfusion conditions, higher robustness to various power/heating time combinations, and superiority to generate deep‐seated lesions through tissues with complex interfaces. Possible mechanisms include the optimization of the thermal conduction created by the strongly focused sonication and the temperature buildup gained from thermally induced tissue attenuation change based on the theoretical analysis. This may represent a useful technique for increasing the applicability of split‐focus and multiple‐focus sonication techniques, and solve the obstacles encountered when attempting to use these methods to shorten the total clinical treatment time.
Quality assurance of the multileaf collimator with helical tomotherapy: Design and implementation
Authors: Sarkar Vikren , Lin Lan , Shi Chengyu , Papanikolaou Niko
Published: July 2007

Quality assurance (QA) of the multileaf collimator (MLC) is a critical step for the delivery of intensity modulated radiation therapy treatment plan. While QA procedures for motor‐driven MLC have been published extensively, those for binary MLCs such as the one used for helical tomotherapy have not been presented in the literature, as this is still a fairly new technology. In this study, seven test patterns for the MLC QA of a helical tomotherapy unit have been designed and implemented. The seven test patterns check the MLC alignment, MLC leakage, MLC timing and MLC leaf position error in detail. Those patterns can be easily implemented in any center with a helical tomotherapy unit as part of the routine QA. The QA procedures can be performed using existing QA resources such as solid water phantom and EDR2 film. A software toolkit called “Tomo MLC QA” has been developed to assist in generating the QA procedures and analyzing the results. Our results showed that the helical tomotherapy MLC is very robust, exhibiting interleaf leakage of . Several issues with the MLC have been found and discussed. The QA results also illustrate the utilization and usefulness of the proposed QA procedures.
Speech recognition as a function of high-pass filter cutoff frequency for people with and without low-frequency cochlear dead regions
Authors: Vinay  , Moore Brian C. J.
Published: July 2007

Regions in the cochlea with no (or very few) functioning inner hair cells and/or neurons are called “dead regions” (DRs). The recognition of high-pass filtered nonsense syllables was measured as a function of filter cutoff frequency for hearing-impaired people with and without low-frequency (apical) cochlear DRs. The diagnosis of any DR was made using the TEN(HL) test, and psychophysical tuning curves were used to define the edge frequency (fe) more precisely. Stimuli were amplified differently for each ear, using the “Cambridge formula.” For subjects with low-frequency hearing loss but without DRs, scores were high (about 78%) for low cutoff frequencies, remained approximately constant for cutoff frequencies up to 862Hz, and then worsened with increasing cutoff frequency. For subjects with low-frequency DRs, performance was typically poor for the lowest cutoff frequency (100Hz), improved as the cutoff frequency was increased to about 0.57fe, and worsened with further increases. These results indicate that people with low-frequency DRs are able to make effective use of frequency components that fall in the range 0.57fe to fe, but that frequency components below 0.57fe have deleterious effects. The results have implications for the fitting of hearing aids to people with low-frequency DRs.
A multiple degree of freedom electromechanical Helmholtz resonator
Authors: Liu Fei , Horowitz Stephen , Nishida Toshikazu , Cattafesta Louis , Sheplak Mark
Published: July 2007

The development of a tunable, multiple degree of freedom (MDOF) electromechanical Helmholtz resonator (EMHR) is presented. An EMHR consists of an orifice, backing cavity, and a compliant piezoelectric composite diaphragm. Electromechanical tuning of the acoustic impedance is achieved via passive electrical networks shunted across the piezoceramic. For resistive and capacitive loads, the EMHR is a 2DOF system possessing one acoustic and one mechanical DOF. When inductive ladder networks are employed, multiple electrical DOF are added. The dynamics of the multi-energy domain system are modeled using lumped elements and are represented in an equivalent electrical circuit, which is used to analyze the tunable acoustic input impedance of the EMHR. The two-microphone method is used to measure the acoustic impedance of two EMHR designs with a variety of resistive, capacitive, and inductive shunts. For the first design, the data demonstrate that the tuning range of the second resonant frequency for an EMHR with non-inductive shunts is limited by short- and open-circuit conditions, while an inductive shunt results in a 3DOF system possessing an enhanced tuning range. The second design achieves stronger coupling between the Helmholtz resonator and the piezoelectric backplate, and both resonant frequencies can be tuned with different non-inductive loads.
Representation of the vowel /ε/ in normal and impaired auditory nerve fibers: Model predictions of responses in cats
Authors: Zilany Muhammad S. A. , Bruce Ian C.
Published: July 2007

The temporal response of auditory-nerve (AN) fibers to a steady-state vowel is investigated using a computational auditory-periphery model. The model predictions are validated against a wide range of physiological data for both normal and impaired fibers in cats. The model incorporates two parallel filter paths, component 1 (C1) and component 2 (C2), which correspond to the active and passive modes of basilar membrane vibration, respectively, in the cochlea. The outputs of the two filters are subsequently transduced by two separate functions, added together, and then low-pass filtered by the inner hair cell (IHC) membrane, which is followed by the IHC-AN synapse and discharge generator. The C1 response dominates at low and moderate levels and is responsible for synchrony capture and multiformant responses seen in the vowel responses. The C2 response dominates at high levels and contributes to the loss of synchrony capture observed in normal and impaired fibers. The interaction between C1 and C2 responses explains the behavior of AN fibers in the transition region, which is characterized by two important observations in the vowel responses: First, all components of the vowel undergo the C1/C2 transition simultaneously, and second, the responses to the nonformant components of the vowel become substantial.
Experimental ultrasound characterization of red blood cell aggregation using the structure factor size estimator
Authors: Yu François T. H. , Cloutier Guy
Published: July 2007

The frequency dependence of the ultrasonic backscattering coefficient (BSC) was studied to assess the level of red blood cell (RBC) aggregation. Three monoelement focused wideband transducers were used to insonify porcine blood sheared in a Couette flow from 9to30MHz. A high shear rate was first applied to promote disaggregation. Different residual shear rates were then used to promote formation of RBC aggregates. The structure factor size estimator (SFSE), a second-order data reduction model based on the structure factor, was applied to the frequency-dependent BSC. Two parameters were extracted from the model to describe the level of aggregation at 6% and 40% hematocrits: W, the packing factor, and D the aggregate diameter, expressed in number of RBCs. Both parameters closely matched theoretical values for nonaggregated RBCs. W and D increased during aggregation with stabilized values modulated by the applied residual shear rate. Furthermore, parameter D during the kinetics of aggregation at 6% hematocrit under static conditions correlated with an optical RBC aggregate size estimation from microscopic images (r2=0.76). To conclude, the SFSE presents an interesting framework for tissue characterization of partially correlated dense tissues such as aggregated RBCs.
Multi-mode nonlinear resonance ultrasound spectroscopy for defect imaging: An analytical approach for the one-dimensional case
Authors: Van Den Abeele Koen
Published: July 2007

A nonlinear version of the resonance ultrasound spectroscopy (RUS) theory is presented as an extension of the RUS formalism to the treatment of microdamage characterized by nonlinear constitutive equations. General analytical equations are derived for the one-dimensional case, describing the excitation amplitude dependent shift in the resonance frequency and the generation of harmonics resulting from the interaction between bar modes due to the presence of either localized or volumetrically distributed nonlinearity. Solutions are obtained for classical cubic nonlinearity, as well as for the more interesting case of hysteresis nonlinearity. The analytical results are in excellent quantitative agreement with numerical calculations from a multiscale model. Finally, the analytical formulas are exploited to infer critical information about damage position, degree of nonlinearity, and width of the damage zone either from the shifts in resonance frequency occurring at different excitation modes, or from the shift and the harmonics predicted at a single mode. Unlike other techniques, the multi-mode-nonlinear RUS method does not require a spatial scan to locate the defect, as it lets different excitation modes, with different vibration patterns, probe the structure. Two general methods are suggested for inverting experimental data.
The dependence of time-domain speed-of-sound measurements on center frequency, bandwidth, and transit-time marker in human calcaneusin vitro
Authors: Wear Keith A.
Published: July 2007

Time-domain speed-of-sound (SOS) measurements in calcaneus are effective predictors of osteoporotic fracture risk. High attenuation and dispersion in bone, however, produce severe distortion of transmitted pulses that leads to ambiguity of time-domain SOS measurements. An equation to predict the effects of system parameters (center frequency and bandwidth), algorithm parameters (pulse arrival-time marker), and bone properties (attenuation coefficient and thickness) on time-domain SOS estimates is derived for media with attenuation that varies linearly with frequency. The equation is validated using data from a bone-mimicking phantom and from 30 human calcaneus samples in vitro. The data suggest that the effects of dispersion are small compared with the effects of frequency-dependent attenuation. The equation can be used to retroactively compensate data. System-related variations in SOS are shown to decrease as the pulse-arrival-time marker is moved toward the pulse center. Therefore, compared with other time-domain measures of SOS, group velocity exhibits the minimum system dependence.
Active listening room compensation for massive multichannel sound reproduction systems using wave-domain adaptive filtering
Authors: Spors Sascha , Buchner Herbert , Rabenstein Rudolf , Herbordt Wolfgang
Published: July 2007

The acoustic theory for multichannel sound reproduction systems usually assumes free-field conditions for the listening environment. However, their performance in real-world listening environments may be impaired by reflections at the walls. This impairment can be reduced by suitable compensation measures. For systems with many channels, active compensation is an option, since the compensating waves can be created by the reproduction loudspeakers. Due to the time-varying nature of room acoustics, the compensation signals have to be determined by an adaptive system. The problems associated with the successful operation of multichannel adaptive systems are addressed in this contribution. First, a method for decoupling the adaptation problem is introduced. It is based on a generalized singular value decomposition and is called eigenspace adaptive filtering. Unfortunately, it cannot be implemented in its pure form, since the continuous adaptation of the generalized singular value decomposition matrices to the variable room acoustics is numerically very demanding. However, a combination of this mathematical technique with the physical description of wave propagation yields a realizable multichannel adaptation method with good decoupling properties. It is called wave domain adaptive filtering and is discussed here in the context of wave field synthesis.
Acoustic scattering in dispersions: Improvements in the calculation of single particle scattering coefficients
Authors: Pinfield Valerie J.
Published: July 2007

Measurements of ultrasound speed and attenuation can be related to the properties of dispersed systems by applying a scattering model. Rayleigh’s method for scattering of sound by a spherical object, and its subsequent developments to include viscous, thermal, and other effects (known as the ECAH model) has been widely adopted. The ECAH method has difficulties, including numerical ill-conditioning, calculation of Bessel functions at large arguments, and inclusion of thermal effects in all cases. The present work develops techniques for improving the ECAH calculations to allow its use in instrumentation. It is shown that thermal terms can be neglected in some boundary equations up to ∼100GHz in water, and several simplified solutions result. An analytical solution for the zero-order coefficient is presented, with separate nonthermal and thermal parts, allowing estimation of the thermal contribution. Higher orders have been simplified by estimating the small shear contribution as the inertial limit is approached. The condition of the matrix solutions have been greatly improved by these techniques and by including appropriate scaling factors. A method is presented for calculating the required Bessel functions when the argument is large (high frequency or large particle size). The required number of partial wave orders is also considered.
Front-back confusion resolution in three-dimensional sound localization using databases built with a dummy head
Authors: Ovcharenko Alexander , Cho Sang Jin , Chong Ui-Pil
Published: July 2007

Sound localization plays an important role in everyday life. It helps us to separate sounds coming from different sources and thus to acquire acoustic information. This paper describes an algorithm for localizing the position of a sound source, as recorded by dummy head microphones. The recorded signals are considered to be basic, random signals within an imaginary round room. The goal of this research is to localize random signals produced from different positions using information about basic signals. The method used is based on the identification of similarities between basic and random signals. It includes an interaural time difference comparison at the beginning, and continues with further analysis of the differences in signal spectrums. One of the main issues arising in sound localization is the problem of front-back confusion, and this paper shows how it was resolved by the use of reference signals.
Reproducibility experiments on measuring acoustical properties of rigid-frame porous media (round-robin tests)
Authors: Horoshenkov Kirill V. , Khan Amir , Bécot François-Xavier , Jaouen Luc , Sgard Franck , Renault Amélie , Amirouche Nesrine , Pompoli Francesco , Prodi Nicola , Bonfiglio Paolo , Pispola Giulio , Asdrubali Francesco , Hübelt Jörn , Atalla Noureddine , Amédin Celse K. , Lauriks Walter , Boeckx Laurens
Published: July 2007

This paper reports the results of reproducibility experiments on the interlaboratory characterization of the acoustical properties of three types of consolidated porous media: granulated porous rubber, reticulated foam, and fiberglass. The measurements are conducted in several independent laboratories in Europe and North America. The studied acoustical characteristics are the surface complex acoustic impedance at normal incidence and plane wave absorption coefficient which are determined using the standard impedance tube method. The paper provides detailed procedures related to sample preparation and installation and it discusses the dispersion in the acoustical material property observed between individual material samples and laboratories. The importance of the boundary conditions, homogeneity of the porous material structure, and stability of the adopted signal processing method are highlighted.
Theoretical feasibility of suppressing offensive sports chants by means of delayed feedback of sound
Authors: van Wijngaarden Sander J. , van Balken Johan A.
Published: July 2007

A novel approach for disrupting offensive chants at sporting events is proposed, based on attacking synchronization between individuals. Since timing is crucial for coordination between chanters, disruption of timing is expected to be effective against undesired chants. Delayed auditory feedback is known to disrupt timing in individual sound production. It may be expected to have similar effects on groups of chanters. To test this hypothesis, a controlled laboratory study was carried out. This showed that the timing of individuals joining in with sports chants can indeed be severely disrupted by also presenting an artificially delayed version of this chant (distracter). This effect is reduced as an individual is given more cues (direction, fidelity) to differentiate between original chant and distracter. However, informal field trials showed that it may be hard to exploit the perceptual effects discussed here for countering offending sports chants in a real-life setting, particularly due to feedback distortion at the required high levels.
Vowel formants from the wave equation
Authors: Hannukainen Antti , Lukkari Teemu , Malinen Jarmo , Palo Pertti
Published: July 2007

This article describes modal analysis of acoustic waves in the human vocal tract while the subject is pronouncing [øː]. The model used is the wave equation in three dimensions, together with physically relevant boundary conditions. The geometry is reconstructed from anatomical MRI data obtained by other researchers. The computations are carried out using the finite element method. The model is validated by comparing the computed modes with measured data.
Sounds recorded in the presence of Blainville’s beaked whales, Mesoplodon densirostris, near Hawai’i
Authors: Rankin Shannon , Barlow Jay
Published: July 2007

During a combined visual and acoustic cetacean survey of the Hawaiian Islands in 2002, four midfrequency sounds were recorded in close proximity to a group of Blainville’s beaked whales, Mesoplodon densirostris. These sounds included one frequency-modulated whistle, and three frequency- and amplitude-modulated pulsed sounds, with energy between 6 and 16kHz. Until recently, little was known of the acoustic behavior of beaked whales, and early descriptions of audible sounds made by beaked whales are incomplete [Caldwell and Caldwell, Cetology 4, 1–5 (1971); Lynn and Reiss, Marine Mammal Sci. 8(3), 229–305 (1992); T. C. Poulter, “Marine mammals,” in Animal Communication; Techniques of Study and Results of Research, edited by T. A. Sebeok (Indiana University Press, Bloomington, 1968)]. Recent recordings of high-frequency clicks (>20kHz, [Johnson et al., Proc. R. Soc. London, Ser. B (Suppl.) 271, 5383–5386 (2004); Zimmer et al., J. Acoust. Soc. Am. 117(6), 3919–3927.]) were above the frequency response of our equipment, and therefore not detected. Sound production within the midfrequency range of sounds described here suggests that the hearing of M. densirostris is sensitive at frequencies used in some types of active sonars.
Fundamental study on subharmonic imaging by irradiation of amplitude-modulated ultrasound waves
Authors: Maikusa Norihide , Fukami Tadanori , Yuasa Tetsuya , Tamura Yasutaka , Akatsuka Takao
Published: July 2007

The second harmonic and subharmonic components, the frequencies of which are twice and one half the fundamental frequency, are included in echoes from contrast agents. An imaging method, which employs a second harmonic (second harmonic imaging), is widely used in medical diagnoses. On the other hand, subharmonic is expected to provide a higher contrast between biological tissues and blood flow because echo signals are generated only from blood containing the contrast agents. However, the subharmonic component echo signal power from contrast agents is relatively low. This has resulted in little progress in the field of subharmonic imaging. In this study, a new imaging method is proposed using amplitude-modulated waves as transmitted waves combined with the pulse inversion method to enhance subharmonic echo signals. Two optimal frequencies are set, including the modulated waves, F1 and F2, so that the subharmonic frequency of F1 and the second harmonic frequency of F2 may result in the same value. This allows a more powerful signal at the frequency band because the second harmonic and subharmonic components are integrated. Furthermore, a B-mode ultrasound image of an agar phantom that imitated biological tissue and showed the effectiveness of our method was reconstructed. As a result, the echo power of the subharmonic component was enhanced by approximately 11.8dB more than the conventional method and the signal to noise ratio showed an improvement of 7.6dB.
A Molecular Basis for Natural Selection at the
timeless
Locus in
Drosophila melanogaster
Authors: Sandrelli Federica , Tauber Eran , Pegoraro Mirko , Mazzotta Gabriella , Cisotto Paola , Landskron Johannes , Stanewsky Ralf , Piccin Alberto , Rosato Ezio , Zordan Mauro , Costa Rodolfo , Kyriacou Charalambos P.
Published: July 2007

Diapause is a protective response to unfavorable environments that results in a suspension of insect development and is most often associated with the onset of winter. The
ls-tim
mutation in the
Drosophila melanogaster
clock gene
timeless
has spread in Europe over the past 10,000 years, possibly because it enhances diapause. We show that the mutant allele attenuates the photosensitivity of the circadian clock and causes decreased dimerization of the mutant TIMELESS protein isoform to CRYPTOCHROME, the circadian photoreceptor. This interaction results in a more stable TIMELESS product. These findings reveal a molecular link between diapause and circadian photoreception.
Regulation of Spontaneous Intestinal Tumorigenesis Through the Adaptor Protein MyD88
Authors: Rakoff-Nahoum Seth , Medzhitov Ruslan
Published: July 2007

Inflammation is increasingly recognized as an important component of tumorigenesis, although the mechanisms and pathways involved are not well understood. Tumor development is regulated by products of several modifier genes, but instructions for their tumor-specific expression are currently unknown. We show that the signaling through the adaptor protein MyD88 has a critical role in spontaneous tumor development in mice with heterozygous mutation in the adenomatous polyposis coli (APC) gene. We found that MyD88-dependent signaling controls the expression of several key modifier genes of intestinal tumorigenesis and has a critical role in both spontaneous and carcinogen-induced tumor development. This study thus reveals the important role of an innate immune signaling pathway in intestinal tumorigenesis.
Reversible Control of Hydrogenation of a Single Molecule
Authors: Katano Satoshi , Kim Yousoo , Hori Masafumi , Trenary Michael , Kawai Maki
Published: July 2007

Low-temperature scanning tunneling microscopy was used to selectively break the N-H bond of a methylaminocarbyne (CNHCH
3
) molecule on a Pt(111) surface at 4.7 kelvin, leaving the C-H bonds intact, to form an adsorbed methylisocyanide molecule (CNCH
3
). The methylisocyanide product was identified through comparison of its vibrational spectrum with that of directly adsorbed methylisocyanide as measured with inelastic electron tunneling spectroscopy. The CNHCH
3
could be regenerated in situ by exposure to hydrogen at room temperature. The combination of tip-induced dehydrogenation with thermodynamically driven hydrogenation allows a completely reversible chemical cycle to be established at the single-molecule level in this system. By tailoring the pulse conditions, irreversible dissociation entailing cleavage of both the C-H and N-H bonds can also be demonstrated.
Identification of Active Edge Sites for Electrochemical H
2
Evolution from MoS
2
Nanocatalysts
Authors: Jaramillo Thomas F. , Jørgensen Kristina P. , Bonde Jacob , Nielsen Jane H. , Horch Sebastian , Chorkendorff Ib
Published: July 2007

The identification of the active sites in heterogeneous catalysis requires a combination of surface sensitive methods and reactivity studies. We determined the active site for hydrogen evolution, a reaction catalyzed by precious metals, on nanoparticulate molybdenum disulfide (MoS
2
) by atomically resolving the surface of this catalyst before measuring electrochemical activity in solution. By preparing MoS
2
nanoparticles of different sizes, we systematically varied the distribution of surface sites on MoS
2
nanoparticles on Au(111), which we quantified with scanning tunneling microscopy. Electrocatalytic activity measurements for hydrogen evolution correlate linearly with the number of edge sites on the MoS
2
catalyst.
Middle Paleolithic Assemblages from the Indian Subcontinent Before and After the Toba Super-Eruption
Authors: Petraglia Michael , Korisettar Ravi , Boivin Nicole , Clarkson Christopher , Ditchfield Peter , Jones Sacha , Koshy Jinu , Lahr Marta Mirazón , Oppenheimer Clive , Pyle David , Roberts Richard , Schwenninger Jean-Luc , Arnold Lee , White Kevin
Published: July 2007

The Youngest Toba Tuff (YTT) eruption, which occurred in Indonesia 74,000 years ago, is one of Earth's largest known volcanic events. The effect of the YTT eruption on existing populations of humans, and accordingly on the course of human evolution, is debated. Here we associate the YTT with archaeological assemblages at Jwalapuram, in the Jurreru River valley of southern India. Broad continuity of Middle Paleolithic technology across the YTT event suggests that hominins persisted regionally across this major eruptive event.
Ancient Biomolecules from Deep Ice Cores Reveal a Forested Southern Greenland
Authors: Willerslev Eske , Cappellini Enrico , Boomsma Wouter , Nielsen Rasmus , Hebsgaard Martin B. , Brand Tina B. , Hofreiter Michael , Bunce Michael , Poinar Hendrik N. , Dahl-Jensen Dorthe , Johnsen Sigfus , Steffensen Jørgen Peder , Bennike Ole , Schwenninger Jean-Luc , Nathan Roger , Armitage Simon , de Hoog Cees-Jan , Alfimov Vasily , Christl Marcus , Beer Juerg , Muscheler Raimund , Barker Joel , Sharp Martin , Penkman Kirsty E. H. , Haile James , Taberlet Pierre , Gilbert M. Thomas P. , Casoli Antonella , Campani Elisa , Collins Matthew J.
Published: July 2007

It is difficult to obtain fossil data from the 10% of Earth's terrestrial surface that is covered by thick glaciers and ice sheets, and hence, knowledge of the paleoenvironments of these regions has remained limited. We show that DNA and amino acids from buried organisms can be recovered from the basal sections of deep ice cores, enabling reconstructions of past flora and fauna. We show that high-altitude southern Greenland, currently lying below more than 2 kilometers of ice, was inhabited by a diverse array of conifer trees and insects within the past million years. The results provide direct evidence in support of a forested southern Greenland and suggest that many deep ice cores may contain genetic records of paleoenvironments in their basal sections.
High-Speed Imaging Reveals Neurophysiological Links to Behavior in an Animal Model of Depression
Authors: Airan Raag D. , Meltzer Leslie A. , Roy Madhuri , Gong Yuqing , Chen Han , Deisseroth Karl
Published: July 2007

The hippocampus is one of several brain areas thought to play a central role in affective behaviors, but the underlying local network dynamics are not understood. We used quantitative voltage-sensitive dye imaging to probe hippocampal dynamics with millisecond resolution in brain slices after bidirectional modulation of affective state in rat models of depression. We found that a simple measure of real-time activity—stimulus-evoked percolation of activity through the dentate gyrus relative to the hippocampal output subfield—accounted for induced changes in animal behavior independent of the underlying mechanism of action of the treatments. Our results define a circuit-level neurophysiological endophenotype for affective behavior and suggest an approach to understanding circuit-level substrates underlying psychiatric disease symptoms.
To While Away Some Time ...
Authors: Jasny Barbara , Suter Sherman
Published: July 2007

We offer suggestions of some titles that may reward you for a few hours of reading while reclining on a beach, settled in for a long flight, or lazing in a hammock.
Metabolic Targeting as an Anticancer Strategy: Dawn of a New Era?
Authors: Pan James G. , Mak Tak W.
Published: July 2007

As a result of a spectrum of mitochondrial defects, tumor cells often preferentially use glycolysis to generate adenosine triphosphate (ATP), even in the presence of oxygen, a phenomenon known as aerobic glycolysis, or the "Warburg effect." Dichloroacetate (DCA) is an inhibitor of mitochondrial pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), a gatekeeping enzyme for the entry of pyruvate into the mitochondrial tricarboxylic acid (TCA) cycle. In mice, DCA treatment appears to reactivate mitochondrial respiration in tumor cells, induces their selective killing, and suppresses cancer growth. These observations provide intriguing insights into the plasticity of tumor metabolism that may offer new opportunities for therapeutic intervention.
Regulation of Interferon Production by RIG-I and LGP2: A Lesson in Self-Control
Authors: Vitour Damien , Meurs Eliane F.
Published: July 2007

The cytoplasmic CARD-containing DExD/H box RNA helicases RIG-I and MDA5 act as sensors of viral infections through recognition of viral double-stranded (ds) RNAs. They both associate with the mitochondrial adaptor IPS-1 (also referred to as MAVS, VISA, and CARDIF) through homotypic CARD-CARD interactions. IPS-1, in turn, triggers signaling pathways, including activation of the protein kinases TBK1 and IKKε, responsible for the phosphorylation of IRF3, a key transcription factor involved in interferon (IFN) synthesis, one essential element of the innate immune response. RIG-I remains in an autoinhibited state in the absence of dsRNA, through an internal repressor domain (RD) that binds within both its CARD and its RNA helicase domains and therefore acts in cis to control its multimerization and interaction with IPS-1. Ectopic expression of the RD prevents signaling and increases cell permissiveness to viruses, including hepatitis C virus. LGP2, which is another DExD/H RNA helicase of the RIG-I and MDA5 family and which is devoid of CARD domain, negatively controls IFN induction at different levels: by sequestering dsRNA, by blocking RIG-I’s multimerization in trans through a domain analogous to the RIG-I RD, and by competing with the protein kinase IKKε for a common interaction site on IPS-1. The ability of RIG-I and LGP2 to exert such a feedback control at the earliest steps of IFN synthesis allows the cells to exert a tight regulation of the induction of the innate immune response.
Pulled in the Wrong Direction
Authors: Adler Elizabeth M.
Published: July 2007

Developing
Drosophila
egg chambers consist of germline cells (the oocyte and nurse cells) surrounded by somatic epithelial follicle cells. During development, a group of epithelial cells, the border cells, detach from the epithelium and, guided by secreted growth factors, migrate as a cluster toward the oocyte. Prasad and Montell performed time-lapse video imaging of migrating border cells in organ culture to investigate the dynamics of border cell migration in response to guidance factors. They confirmed previous research from fixed tissue indicating that border cell migration was inhibited in egg chambers coexpressing dominant-negative forms of the PVR (platelet-derived growth factor/vascular

endothelial growth factor receptor) and EGFR (epidermal growth factor receptor) receptor tyrosine kinases. Further, they discovered that, rather than inhibiting the extension of actin-rich protrusions in the direction of migration (as seen in wild-type cells), these mutant receptors elicited substantial numbers of protrusions pointing away from the direction of migration. Cells expressing constitutively active EGFR failed to extend protrusions or detach from the epithelium; cells expressing constitutively active PVR did extend protrusions but also failed to detach. A dominant-negative form of Kuzabian, a metalloproteinase involved in Notch activation (which is necessary for normal border cell migration), elicited a decrease in the frequency of protrusions and an increase in their lifetime and also inhibited detachment from the epithelium. The authors conclude that, rather than stimulating actin polymerization and the formation of protrusions at the leading edge of migrating border cells, guidance receptor signaling provides directionality by inhibiting the extension of protrusions in the wrong direction.

M. Prasad, D. J. Montell, Cellular and molecular mechanisms of border cell migration analyzed using time-lapse live-cell imaging.
Dev. Cell
12
, 997-1005 (2007).
[PubMed]
Comparison of thoracic kyphosis in two groups of elite Greco-Roman and freestyle wrestlers and a group of non-athletic participants
Authors: Rajabi R , Doherty P , Goodarzi M , Hemayattalab R
Published: July 2007

Background:

Freestyle and Greco-Roman are two types of wrestling that place the spine of athletes in different positions. Theoretically, it can be argued that this can lead to adverse effects on the spine and might be an important factor associated with changes in the degree of kyphosis.

Objectives:

The aim of this study was to investigate whether the extent of thoracic kyphosis differs in two groups of elite wrestlers and a group of non-athletic participants.

Methods:

Sixty elite Iranian male wrestlers including 30 freestyle (mean (SD) age 23.5 (2.8) years, height 176 (7.1) cm and weight 77.8 (16.1) kg) and 30 Greco-Roman (age 23.9 (2.9) years, height 176 (4) cm and weight 80.1 (11.1) kg) wrestlers and 30 male non-athletes (age 23.3 (2.1) years, height 175 (8) cm and weight 75.2 (6.7) kg) were recruited. All wrestlers competed at international level with the Iranian national team or Iranian student national team. Each selected wrestler had to meet a minimum criterion of 5 years' wrestling. The degree of kyphosis was measured using a modified electrogoniometer.

Results:

Mean (SD) kyphosis was 30° (3.8), 24.3° (3.7) and 27.4° (3.2) for the freestyle, Greco-Roman style and non-athlete groups, respectively. A significant difference was found in mean kyphosis between all groups (p<0.05) with freestyle being the highest and Greco-Roman the lowest.

Conclusions:

The degree of kyphosis was highest in freestyle wrestling, followed by non-athletes and then Greco-Roman wrestlers. The extent of kyphosis was not influenced by years of training or age of starting wrestling.
Fructose-induced hypertension in Wistar–Kyoto rats: interaction with moderately high dietary saltThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Vasdev Sudesh , Gill Vicki , Parai Sushil , Gadag Vereesh
Published: July 2007

We investigated the effects of 4% fructose plus moderately high salt (MHS) (4% NaCl) treatment on tissue aldehyde conjugates, platelet cytosolic free calcium ([Ca2+]i), renal morphology, and systolic blood pressure (SBP) in Wistar–Kyoto rats, and whether these effects were reversible (R) after withdrawal of treatment. At age 7 weeks, rats were divided into 4 groups: NS group, given normal salt (NS) diet (0.7% NaCl) for 18 weeks; NS+F(R) group, NS diet and fructose in water for 14 weeks, then 4 weeks fructose withdrawal; MHS+F group, NS diet and fructose for 6 weeks, then MHS diet and fructose for 12 weeks; and MHS+F(R) group, NS diet and fructose for 6 weeks, then MHS diet and fructose for 8 weeks, then MHS and fructose withdrawal for 4 weeks. SBP in the NS+F(R) group increased during fructose treatment, but normalized within 1 week of withdrawal. Tissue aldehyde conjugates and platelet [Ca2+]i were normal at completion. Adverse renal vascular changes did not reverse to normal and were similar to those of the salt plus fructose-treated groups. This may have implications for future development of hypertension. MHS did not cause any additional increase in SBP or associated tissue alterations when added to fructose treatment. However, the SBP and tissue changes persisted even after discontinuation of treatment. The fructose and salt combination may result in long-lasting vascular alterations leading to hypertension.
Inhibition of endothelial barrier dysfunction by P21-activated kinase-1This paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Ke Yunbo , Lum Hazel , Solaro R. John
Published: July 2007

We investigated the activity of P21-activated kinase-1 (Pak1) on myosin light chain phosphorylation and on thrombin-induced barrier dysfunction in human endothelial cells (HMEC). HMEC were infected with recombinant adenoviruses that express constitutively active Pak1, LacZ, wild-type, and a mutant myosin regulatory light chain, mMLC20(Thr18Ala, Ser19Ala). Expression of the recombinant Pak1 mediated by adenovirus in HMEC was regulated. Active Pak1 induced dephosphorylation of MLC20in HMEC, but not in smooth muscle cells. Active Pak1 significantly inhibited thrombin-induced endothelial barrier dysfunction. Expression of the unphosphorylatable MLC20also inhibited thrombin-induced endothelial barrier dysfunction. Constitutively active Pak1 associated with phosphatase 2A and induced a post-translational modification of the phosphatase. Our data provide novel evidence indicating that Pak1 regulates endothelial barrier function through activation of phosphatase 2A.
Gender differences in the modulation of cardiac gene expression by dietary conjugated linoleic acid isomersThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Tappia Paramjit S. , Dent Melissa R. , Aroutiounova Nina , Babick Andrea P. , Weiler Hope
Published: July 2007

In an earlier study, we showed that dietary conjugated linoleic acid (CLA) isomers can exert differential effects on heart function in male and female rats, but the underlying mechanisms for these actions are not known. Cardiomyocyte Ca2+ cycling is a key event in normal cardiac contractile function and defects in Ca2+ cycling are associated with cardiac dysfunction and heart disease. We therefore hypothesized that abnormalities in the sarcolemmal (SL) and sarcoplasmic reticulum (SR)-mediated regulation of intracellular Ca2+ contribute to altered cardiac contractile function of male and female rats owing to dietary CLA isomers. Healthy male and female Sprague–Dawley rats were fed different CLA isomers, (cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12)) individually and in combination (50:50 mix as triglyceride or fatty acids) from 4 to 20 weeks of age. We determined the mRNA levels of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 2a, ryanodine receptor, phospholamban, calsequestrin, Na+–Ca2+-exchanger (NCX), and L-type Ca2+ channel in the left ventricle (LV) by RT-PCR. The SR function was assessed by measurement of Ca2+-uptake and -release. Significant gender differences were seen in the LV NCX, L-type Ca2+ channel, and ryanodine receptor mRNA expression levels in control male and female rats. Dietary CLA isomers in the various forms induced changes in the mRNA levels of SERCA 2a, NCX, and L-type Ca2+ channel in the LV of both male and female hearts. Whereas protein contents of the Ca2+ cycling proteins were altered, changes in SR Ca2+-uptake and -release were also detected in both male and female rats in response to dietary CLA. The results of this study demonstrate that long-term dietary supplementation can modulate cardiac gene expression and SR function in a gender-related manner and may, in part, contribute to altered cardiac contractility.
The peptide analogue of MCP-1 65–76 sequence is an inhibitor of inflammationThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Chazov Evgeny I. , Bespalova Janna D. , Arefieva Tatiana I. , Kukhtina Nadezhda B. , Sidorova Maria V. , Provatorov Sergey I. , Krasnikova Tatiana L.
Published: July 2007

Inflammation plays an important role in vessel wall remodeling that occurs in atherosclerosis and postangioplasty restenosis. Monocytic chemoattractant protein-1 (MCP-1) is one of the main attractors of monocytes and some lymphocyte subsets to the damaged vessel. The aims of the study were to confirm MCP-1 participation in the development of acute coronary syndromes, to produce the potential MCP-1 peptide antagonist, and to investigate its effects in vitro and in vivo in different animal models of inflammation. MCP-1 plasma concentration was measured by ELISA (enzyme-linked immunosorbent assay). Chemokine receptor expression by cells isolated from human atherosclerotic lesions was assessed by direct immunofluorescence and flow cytometry. MCP-1 sequence was analyzed with Peptide Companion software and peptides were synthesized using Fmoc strategy. The peptide resistance to degradation was checked by1H-NMR spectroscopy. The peptide effect on MCP-1-stimulated cell migration was studied in Boyden chamber and in mouse air pouch model, and its influence on lipopolysaccharide (LPS)-induced inflammatory cell recruitment was investigated in models of subcutaneous inflammation in rats and nonhuman primates. We revealed nearly a 2-fold increase of MCP-1 plasma level in patients with unstable angina in comparison with patients with stable angina. The atherosclerotic plaque specimens obtained from patients with unstable angina contained a significant amount of chemokine receptor-expressing leukocytes. Peptide from MCP-1 C-terminal 65–76 sequence (peptide X) inhibited MCP-1-stimulated monocytic cell migration in vitro and in vivo. Peptide X labeled with99mTc accumulated specifically at sites of inflammation in rats. Peptide X administrated i.m and i.v. suppressed monocyte and granulocyte recruitment induced by subcutaneous injection of LPS in the back of rats and non-human primates. Our data demonstrate that MCP-1-mediated chemotaxis could be responsible for atherosclerotic plaque “destabilization”. Peptide X may represent a new class of anti-inflammatory drugs to be used in cardiology.
Intracoronary boluses of adenosine and sodium nitroprusside in combination reverses slow/no-reflow during angioplasty: a clinical scenario of ischemic preconditioningThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Parikh Keyur H. , Chag Milan C. , Shah Kanan J. , Shah Urmil G. , Baxi Hemang A. , Chandarana Anish H. , Naik Ajay M. , Shah Joyal N. , Shah Hetal D. , Goyal Ramesh K.
Published: July 2007

No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a patent epicardial vessel, is a serious complication resulting in increased morbidity and mortality. In the present study, we have evaluated the combination therapy of adenosine and sodium nitroprusside administered as sequential intracoronary (IC) boluses on no-reflow during PCI. Seventy-five high risk acute coronary syndrome patients who underwent PCI with evidence of initial less than TIMI (thrombolysis in myocardial infarction) III flow or developed deterioration in TIMI flow during the procedure were randomized to prophylactic administration of multiple boluses of IC saline solution, adenosine (12 µg/bolus) or the combination of adenosine (12 µg/bolus) and sodium nitroprusside (50 µg/bolus), sequentially. Assessment of TIMI and the TMP (tissue myocardial perfusion) grade was done and major adverse cardiac events (MACE) were assessed at the end of 6 months. Slow or no-reflow was persistent in 70% patients receiving saline solution, 31% patients receiving adenosine, and 4% patient receiving the combination. IC injection with saline solution did not produce improvement in TIMI flow or TMP grade. IC injection with combination resulted in greater improvement of TIMI flow and TMP grade. The crossover of patients with no-reflow in saline solution group or adenosine with combination treatment was associated with reestablishment of TIMI II in 4 and TIMI III in 20 patients. Our data suggest that combination therapy of adenosine and nitroprusside is safe and provides better improvement in coronary flow and MACE as compared with IC adenosine alone in cases of impaired flow during coronary interventions.
ELECTRICAL CHARACTERISTICS AND CARRIER LIFETIME MEASUREMENTS IN HIGH VOLTAGE 4H-SIC PIN DIODES
Authors: Losee P. A. , Li C. , Kumar R. J. , Chow T. P. , Bhat I. B. , Gutmann R. J.
Published: July 2007

The key material and device parameters governing the electrical performance of high voltage 4 H - SiC PiN diodes have been investigated using experimental results and numerical simulations. Reverse recovery characteristics show an increase in both carrier lifetime and anode injection efficiency at elevated temperature. Open circuit voltage decay measurements are used to estimate carrier lifetimes (τ≈0.6μ s at T =25° C increasing to τ≈2μ s at T =225° C ) that are comparable to values measured on starting material prior to fabrication using micro-wave photoconductivity decay techniques.
Geometry and Short Channel Effects on Enhancement-Mode n-Channel GaN MOSFETs on p and n-GaN/Sapphire Substrates
Authors: Huang W. , Khan T. , Chow T. P.
Published: July 2007

In this paper, we have fabricated and compared the performance of lateral enhancement-mode GaN MOSFETs with linear and circular geometries. Circular MOSFETs show 2 to 4 orders of magnitude lower leakage current than that of linear MOSFETs. We also studied short channel behaviors and found that they are similar to those previously reported Si MOSFET.