bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing the formation of the first low-mass stars with stellar archaeology
Authors: Frebel Anna , Johnson Jarrett L. , Bromm Volker
Published: July 2007

We investigate the conditions under which the first low-mass stars formed in the Universe by confronting theoretical predictions governing the transition from massive Population III to low-mass Population II stars with recent observational C and/or O abundance data of metal-poor Galactic stars. We introduce a new ‘observer-friendly’ function, the transition discriminant Dtrans, which provides empirical constraints as well as a powerful comparison between the currently available data of metal-poor halo stars and theoretical predictions of the formation of the first low-mass stars (≲ 1 M⊙). Specifically, we compare the empirical stellar results with the theory that fine-structure lines of C and O dominate the transition from Population III to Population II in the early Universe. We find the currently available data for halo stars as well as for dwarf spheroidal (dSph) galaxies and globular clusters to be consistent with this theory. An explanation for the observed lack of metal-poor stars in dSph galaxies and globular clusters is also suggested. Finally, we predict that any star to be found with [Fe/H]≲−4 should have enhanced C and/or O abundances. The high C and O abundances of the two most iron-poor stars are in line with our prediction.
Intracellular Uptake and Phototoxicity of 31,32‐Didehydrophytochlorin‐fullerene Hexaadducts
Authors: Rancan Fiorenza , Helmreich Matthias , Mölich Andreas , Jux Norbert , Hirsch Andreas , Röder Beate , Böhm Fritz
Published: July 2007

C60‐fullerene derivatives are potential building blocks in modular carrier systems for selective tumor targeting. In [5:1] fullerene hexakis adducts, one position can be occupied by an addressing unit (e.g. monoclonal antibody) while the other five positions are suitable for dendrimers or spacers loaded with several drug moieties. This article reports intracellular uptake and phototoxicity of three fullerene hexakis adducts coupled with a different number of photosensitizers: a bis(31,32‐didehydrophytochlorin)‐fullerene [5:1]‐hexaadduct (FHP1), a fullerene [5:1]‐hexaadduct with six 31,32‐didehydrophytochlorin groups (FHP6) and a fullerene [6:0]‐hexaadduct that carries 12 31,32‐didehydrophytochlorin units (FHP12).

The most promising complex, the hexa‐31,32‐didehydrophytochlorin fullerene hexaadduct FHP6, was also compared with its fullerene‐free analogous derivative P6. It was found that the extent of intracellular uptake is influenced by both nanomolecular size and asymmetry (amphiphilicity) of the fullerene complexes. The degree and mechanism of phototoxicity was found to depend on intracellular concentrations and singlet oxygen quantum yields.
Distinct Responses of Chloroplasts to Blue and Green Laser Microbeam Irradiations in the Centric Diatom Pleurosira laevis
Authors: Shihira‐Ishikawa Ikuko , Nakamura Takanori , Higashi Sho‐ichi , Watanabe Masakatsu
Published: July 2007

The centric diatomPleurosira laevis is a large unicellular alga, in which ca 200 chloroplasts migrate toward the nuclear cytoplasm through the transvacuolar cytoplasmic strands in response to blue‐light irradiation and, on the contrary, toward the cortical cytoplasm in response to green‐light irradiation. We analyzed these light‐induced chloroplast migrations using a scanning laser microbeam provided by a confocal microscope for intracellular irradiation. Spot irradiation of a blue laser microbeam induced rapid assemblage of chroloplasts into the nuclear cytoplasm regardless of the spot position and spot number. On the other hand, one or two spots of green laser microbeam induced chloroplast accumulation at the spots, although increasing spot numbers suppressed chloroplast accumulation at each spot. In our experimental condition, ca 1 min of blue‐light irradiation was sufficient to stimulate movement, whereas green‐light irradiation required uninterrupted and longer irradiation time (ca 15 min). Chloroplast assemblage induced by blue‐light required extracellular Ca2+, and was inhibited by Ca2+channel antagonists. Furthermore, higher efficiencies of chloroplast migration were obtained when a single beam spot was fragmented and scattered over wider area of plasma membrane. These observations suggested that blue‐light induced a response at the plasma membrane, which subsequently activated Ca2+permeable channels. This sequence of physiological events is identical to what was previously observed with chloroplast movement in response to mechanical stimulation. Furthermore, experiments with the cytoskeleton‐disrupting agents, colchicine and cytochalasin D, indicated that blue‐light‐induced chloroplast movement required microtubules whereas the green‐light‐induced response to beam spot required actin filaments.
Study of UV Radiation Dose Received by the Spanish Population
Authors: Gurrea Gonzalo , Cañada Javier
Published: July 2007

Excess exposure to UV radiation can affect our health by causing sunburn, skin cancer, etc. It is therefore useful to determine the UV dosage received by people as a way of protecting them from the possible negative effects that this kind of radiation can cause. In this work, the personal outdoor percentage, which shows the time spent in outdoor activities, as well as personal UV doses, has been calculated by means of global UV radiation on a horizontal plane. A database of average daily UVB radiation on the horizontal plane given by the National Institute of Meteorology has been used. In this work we evaluate the standard erythema dose of the Spanish population throughout the year.
Ratiometric Analysis of Fluorescence Lifetime for Probing Binding Sites in Albumin with Near‐Infrared Fluorescent Molecular Probes
Authors: Berezin Mikhail Y. , Lee Hyeran , Akers Walter , Nikiforovich Gregory , Achilefu Samuel
Published: July 2007

A number of diseases have been linked to abnormal conformation of albumin, a major extracellular protein in blood. Current protein structural analysis requires pure isolated samples, thereby limiting their use for albumin analysis in blood. In this study, we report a new approach for high‐throughput structure‐related analysis of albumin by using the fluorescence lifetime properties of near‐infrared (NIR) polymethine dyes. Based on molecular modeling, polymethine dyes are bound to two binding sites with different polarities on albumin. As a result, an NIR molecular probe exhibits two distinct lifetimes with two corresponding fluorescent fractional contributions. The distribution of fractional contributions along with individual fluorescence lifetimes represents unique parameters for characterizing albumin architecture by ratiometric analysis. After screening a small library of NIR polymethine dyes, we identified and used a polymethine dye with optimal fluorescence lifetime properties to assess structure‐related differences in commercially available bovine serum albumin as model systems. The results show that changes in the lifetime of NIR dyes reflect the perturbation of the tertiary structures of albumin and that albumin prepared by different methods has slightly altered tertiary structures. Because of the reduced absorption of light by blood in the NIR region, the method developed can be used to determine structural changes in albumin in whole blood without prior isolation of the pure protein.
Effect of localized innervation of the dendritic trees of feline motoneurons on the amplification of synaptic input: a computational study
Authors: Grande Giovanbattista , Bui Tuan V. , Rose P. Ken
Published: July 2007

Previous studies show that the activation of voltage‐dependent channels is dependent on the local density of synapses in the dendritic region containing voltage‐dependent channels. We hypothesized that the selective innervation of excitatory vestibulospinal (VST) neurons on the medial dendrites of contralateral splenius motoneurons is designed to enhance the activation of persistent inward currents (PICs) mediated by dendritic L‐type Ca2+ channels. Using compartmental models of splenius motoneurons we compared the synaptic current reaching the soma in response to excitatory input generated by synapses with two different distribution patterns. The medial distribution was based on the arrangement of VST synapses on the dendrites of contralateral splenius motoneurons and the uniform distribution was based on an arrangement of synapses with no particular bias to any region of the dendritic tree. The number of synapses in each distribution was designed to match estimates of the number of VST synapses activated by head movements. In the absence of PICs, the current delivered by the synapses in the uniform distribution was slightly greater. However, the maximal currents were small, ≤ 4.1 nA, regardless of the distribution of synapses. In models equipped with L‐type Ca2+ channels, PIC activation was largely determined by the local density of synapses in proximity to the L‐type Ca2+ channels. In 3 of 5 cells, this led to a 2‐ to 4‐fold increase in the current generated by synapses in the medial distribution compared to the uniform distribution. In the other two cells, the amplification bias was in favour of the medial distribution but was either small or restricted to a narrow range of frequencies. These simulations suggest that the innervation pattern of VST axons on contralateral splenius motoneurons is arranged to strengthen an otherwise weak synaptic input by increasing the likelihood of activating PICs. Additional simulations suggest that this prediction can be tested using common experimental protocols.
Accuracy of tumor motion compensation algorithm from a robotic respiratory tracking system: A simulation study
Authors: Seppenwoolde Yvette , Berbeco Ross I. , Nishioka Seiko , Shirato Hiroki , Heijmen Ben
Published: July 2007

The Synchrony™ Respiratory Tracking System (RTS) is a treatment option of the CyberKnife robotic treatment device to irradiate extra‐cranial tumors that move due to respiration. Advantages of RTS are that patients can breath normally and that there is no loss of linac duty cycle such as with gated therapy. Tracking is based on a measured correspondence model (linear or polynomial) between internal tumor motion and external (chest/abdominal) marker motion. The radiation beam follows the tumor movement via the continuously measured external marker motion. To establish the correspondence model at the start of treatment, the 3D internal tumor position is determined at 15 discrete time points by automatic detection of implanted gold fiducials in two orthogonal x‐ray images; simultaneously, the positions of the external markers are measured. During the treatment, the relationship between internal and external marker positions is continuously accounted for and is regularly checked and updated. Here we use computer simulations based on continuously and simultaneously recorded internal and external marker positions to investigate the effectiveness of tumor tracking by the RTS. The Cyberknife does not allow continuous acquisition of x‐ray images to follow the moving internal markers (typical imaging frequency is once per minute). Therefore, for the simulations, we have used data for eight lung cancer patients treated with respiratory gating. All of these patients had simultaneous and continuous recordings of both internal tumor motion and external abdominal motion. The available continuous relationship between internal and external markers for these patients allowed investigation of the consequences of the lower acquisition frequency of the RTS. With the use of the RTS, simulated treatment errors due to breathing motion were reduced largely and consistently over treatment time for all studied patients. A considerable part of the maximum reduction in treatment error could already be reached with a simple linear model. In case of hysteresis, a polynomial model added some extra reduction. More frequent updating of the correspondence model resulted in slightly smaller errors only for the few recordings with a time trend that was fast, relative to the current x‐ray update frequency. In general, the simulations suggest that the applied combined use of internal and external markers allow the robot to accurately follow tumor motion even in the case of irregularities in breathing patterns.
Self‐consistent tumor control probability and normal tissue complication probability models based on generalized EUDa)
Authors: Zhou Su‐Min , Das Shiva K. , Wang Zhiheng , Sun Xuejun , Dewhirst Mark , Yin Fang‐Fang , Marks Lawrence B.
Published: July 2007

Traditional methods to compute the tumor control probability (TCP) or normal tissue complication probability (NTCP) typically require a heterogeneous radiation dose distribution to be converted into a simple uniform dose distribution with an equivalent biological effect. Several power‐law type dose‐volume‐histogram reduction schemes, particularly Niemierko's generalized equivalent uniform dose model [Med. Phys. 26, 1000 (1999)], have been proposed to achieve this goal. In this study, we carefully examine the mathematical outcome of these schemes. We demonstrate that (1) for tumors, with each tumor cell independently responding to local radiation dose, a closed‐form analytical solution for tumor survival fraction and TCP can be obtained; (2) for serial structured normal tissues, an exponential power‐law form relating survival to functional sub‐unit (FSU) radiation is required, and a closed‐form analytical solution for the related NTCP is provided; (3) in the case of a parallel structured normal tissue, when NTCP is determined solely by the number of the surviving FSUs, a mathematical solution is available only when there is a non‐zero threshold dose and/or a finite critical dose defining the radiotherapy response. Some discussion is offered for the partial irradiation effect on normal tissues in this category; (4) for normal tissues with alternative architectures, where the radiation response of FSU is inhomogeneous, there is no exact global mathematical solution for SF or NTCP within the available schemes. Finally, numerical fits of our models to some experimental data are also presented.
Optimization of slice sensitivity profile for radiographic tomosynthesis
Authors: Li Baojun , Avinash Gopal B. , Eberhard Jeffrey W. , Claus Bernhard E. H.
Published: July 2007

Similar to other tomographic imaging modalities, the slice sensitivity profile (SSP) is an important image quality metric for radiographic tomosynthesis. In this study, the relationship between the acquisition angular range and the SSP for the linear trajectory system was carefully investigated from both theoretical and experimental perspectives. A mathematical SSP model was derived for arbitrary points in the reconstructed volume. We used a newly developed flat‐panel tomosynthesis prototype system to experimentally validate the mathematical model from to angular ranges. The SSP was measured by imaging an edge phantom placed at an angle with respect to the detector plane using the modulation transfer function degradation (MTF‐d) method. In addition to the experiments, computer simulations were performed to investigate the relationship in a wider angular range ( to ). Furthermore, image data from an anthropomorphic phantom were collected to corroborate the system analysis. All the images in this study were constructed using a 3D view‐weighted cone‐beam filtered backprojection algorithm (3D VW CB‐FBP). The theoretical analysis reveals that the SSP of linear trajectory tomosynthesis is inversely proportional to . This theory was supported by both simulation (, , ) and phantom experiment (, ) and was further confirmed by an analysis of the reconstructed images of an anthropomorphic phantom. The results imply that the benefit of narrower SSP by increasing angular range quickly diminishes once beyond . The advantages of the MTF‐d method were also demonstrated.
Determination of subjective similarity for pairs of masses and pairs of clustered microcalcifications on mammograms: Comparison of similarity ranking scores and absolute similarity ratings
Authors: Muramatsu Chisako , Li Qiang , Schmidt Robert A. , Shiraishi Junji , Suzuki Kenji , Newstead Gillian M. , Doi Kunio
Published: July 2007

The presentation of images that are similar to that of an unknown lesion seen on a mammogram may be helpful for radiologists to correctly diagnose that lesion. For similar images to be useful, they must be quite similar from the radiologists’ point of view. We have been trying to quantify the radiologists’ impression of similarity for pairs of lesions and to establish a “gold standard” for development and evaluation of a computerized scheme for selecting such similar images. However, it is considered difficult to reliably and accurately determine similarity ratings, because they are subjective. In this study, we compared the subjective similarities obtained by two different methods, an absolute rating method and a 2‐alternative forced‐choice (2AFC) method, to demonstrate that reliable similarity ratings can be determined by the responses of a group of radiologists. The absolute similarity ratings were previously obtained for pairs of masses and pairs of microcalcifications from five and nine radiologists, respectively. In this study, similarity ranking scores for eight pairs of masses and eight pairs of microcalcifications were determined by use of the 2AFC method. In the first session, the eight pairs of masses and eight pairs of microcalcifications were grouped and compared separately for determining the similarity ranking scores. In the second session, another similarity ranking score was determined by use of mixed pairs, i.e., by comparison of the similarity of a mass pair with that of a calcification pair. Four pairs of masses and four pairs of microcalcifications were grouped together to create two sets of eight pairs. The average absolute similarity ratings and the average similarity ranking scores showed very good correlations in the first study (Pearson's correlation coefficients: 0.94 and 0.98 for masses and microcalcifications, respectively). Moreover, in the second study, the correlations between the absolute ratings and the ranking scores were also very high (0.92 and 0.96), which implies that the observers were able to compare the similarity of a mass pair with that of a calcification pair consistently. These results provide evidence that the concept of similarity for pairs of images is robust, even across different lesion types, and that radiologists are able to reliably determine subjective similarity for pairs of breast lesions.
Evaluation of the precision of portal‐image‐guided head‐and‐neck localization: An intra‐ and interobserver study
Authors: Court Laurence E. , Allen Aaron , Tishler Roy
Published: July 2007

There is increasing evidence that, for some patients, image‐guided intensity‐modulated radiation therapy (IMRT) for head‐and‐neck cancer patients may maintain target dose coverage and critical organ (e.g., parotids) dose closer to the planned doses than setup using lasers alone. We investigated inter‐ and intraobserver uncertainties in patient setup in head‐and‐neck cancer patients. Twenty‐two sets of orthogonal digital portal images (from five patients) were selected from images used for daily localization of head‐and‐neck patients treated with IMRT. To evaluate interobserver variations, five radiation therapists compared the portal images with the plan digitally reconstructed radiographs and reported shifts for the isocenter and for a supraclavicular reference point. One therapist repeated the procedure a month later to evaluate intraobserver variations. The procedure was then repeated with teams of two therapists. The frequencies for which agreement between the shift reported by the observer and the daily mean shift (average of all observers for a given image set) were less than 1.5 and were calculated. Standard errors of measurement for the intra‐ and interobserver uncertainty ( and ) for the individual and teams were calculated. The data showed that there was very little difference between individual therapists and teams. At isocenter, 80%–90% of all reported shifts agreed with the daily average within , showing consistency in the ways both individuals and teams interpret the images . This dropped to 65% for the supraclavicular point . Uncertainties increased for larger setup errors. In conclusion, image‐guided patient positioning allows head‐and‐neck patients to be controlled within . This is similar to the setup uncertainties found for most head‐and‐neck patients, but may provide some improvement for the subset of patients with larger setup uncertainties.
An investigation of dose changes for therapeutic kilovoltage x‐ray beams with underlying lead shielding
Authors: Hill Robin , Healy Brendan , Holloway Lois , Baldock Clive
Published: July 2007

Kilovoltage x‐ray beams are used to treat cancer on or close to the skin surface. Many clinical cases use high atomic number materials as shielding to reduce dose to underlying healthy tissues. In this work, we have investigated the effect on both the surface dose and depth doses in a water phantom with lead shielding at depth in the phantom. The EGSnrc Monte Carlo code was used to simulate the water phantom and to calculate the surface doses and depth doses using primary x‐ray beam spectra derived from an analytical model. The x‐ray beams were in the energy range of 75–with field sizes of 2, 5 anddiameter. The lead sheet was located beneath the water surface at depths ranging from 0.5–. The surface dose decreased as the lead was positioned closer to the water surface and as the field size was increased. The variation in surface dose as a function of x‐ray beam energy was only small but the maximum reduction occurred for thex‐ray beam. For the 8 cm diameter field with the lead atdepth and using thex‐ray beam, the surface dose was reduced to 0.898 of the surface dose in the water phantom only. Measured surface dose changes, using a Farmer‐type ionization chamber, agreed with the Monte Carlo calculated doses. Calculated depth doses in water with a lead sheet positioned below the surface showed that the dose fall‐off increased as the lead was positioned closer to the water surface as compared to the depth dose in the water phantom only. Monte Carlo calculations of the total x‐ray beam spectrum at the water surface showed that the total fluence decreased due to a reduction in backscatter from within the water and very little backscatter from the lead. The mean energy of the x‐ray spectrum varied less than, with the lead atbeneath the water phantom surface. As the Monte Carlo calculations showed good agreement with the measured results, this method can be used to verify surface dose changes in clinical situations where measurements are difficult. The clinical impact of the use of lead must be considered in the dose prescription for patients being treated with kilovoltage x‐ray beams.
Characteristics of surface sound pressure and absorption of a finite impedance strip for a grazing incident plane wave
Authors: Sum K. S. , Pan J.
Published: July 2007

Distributions of sound pressure and intensity on the surface of a flat impedance strip flush-mounted on a rigid baffle are studied for a grazing incident plane wave. The distributions are obtained by superimposing the unperturbed wave (the specularly reflected wave as if the strip is rigid plus the incident wave) with the radiated wave from the surface vibration of the strip excited by the unperturbed pressure. The radiated pressure interferes with the unperturbed pressure and distorts the propagating plane wave. When the plane wave propagates in the baffle-strip-baffle direction, it encounters discontinuities in acoustical impedance at the baffle-strip and strip-baffle interfaces. The radiated pressure is highest around the baffle-strip interface, but decreases toward the strip-baffle interface where the plane wave distortion reduces accordingly. As the unperturbed and radiated waves have different magnitudes and superimpose out of phase, the surface pressure and intensity increase across the strip in the plane wave propagation direction. Therefore, the surface absorption of the strip is nonzero and nonuniform. This paper provides an understanding of the surface pressure and intensity behaviors of a finite impedance strip for a grazing incident plane wave, and of how the distributed intensity determines the sound absorption coefficient of the strip.
Theoretical simulation of electroacoustic borehole logging in a fluid-saturated porous formation
Authors: Hu Hengshan , Guan Wei , Harris Jerry M.
Published: July 2007

Electroacoustic (E-A) logging describes the acoustic response to an electromagnetic (EM) source in a fluid-filled borehole surrounded by a porous medium. The E-A response is simulated by two different methods in this paper. In the coupled method, the EM field and the acoustic field are modeled using Pride’s model, which couples Maxwell’s equations and Biot’s equations. In the uncoupled method, the EM field is uninfluenced by the converted acoustic field, resulting in separate acoustic formulation with an electrokinetic source term derived from the primary EM field. The difference of the transient full waveforms between the above two methods is remarkably small for all examples, thus confirming the validity of using the computationally simpler uncoupled method. It is shown from the simulated waveforms that an EM-accompanying acoustic field is coupled to the EM field and appears with an apparent phase velocity of the EM wave in the formation. Acoustic waves with the conventional acoustic velocities are also seen in the converted full waveforms. For the sandstone models used in this paper, when permeability is less than 1Darcy, the E-A Stoneley wave amplitude increases with porosity, which is different from that in conventional acoustic-to-acoustic logging.
Sound quality characteristics of refrigerator noise in real living environments with relation to psychoacoustical and autocorrelation function parameters
Authors: Sato Shin-ichi , You Jin , Jeon Jin Yong
Published: July 2007

Psychoacoustical and autocorrelation function (ACF) parameters were employed to describe the temporal fluctuations of refrigerator noise during starting, transition into/from the stationary phase and termination of operation. The temporal fluctuations of refrigerator noise include a click at start-up, followed by a rapid increase in volume, a change of pitch, and termination of the operation. Subjective evaluations of the noise of 24 different refrigerators were conducted in a real living environment. The relationship between objective measures and perceived noisiness was examined by multiple regression analysis. Sound quality indices were developed based on psychoacoustical and ACF parameters. The psychoacoustical parameters found to be important for evaluating noisiness in the stationary phase were loudness and roughness. The relationship between noisiness and ACF parameters shows that sound energy and its fluctuations are important for evaluating noisiness. Also, refrigerator sounds that had a fluctuation of pitch were rated as more annoying. The tolerance level for the starting phase of refrigerator noise was found to be 33dBA, which is the level where 65% of the participants in the subjective tests were satisfied.
Plane wave source with minimal harmonic distortion for investigating nonlinear acoustic properties
Authors: Lloyd Christopher W. , Wallace Kirk D. , Holland Mark R. , Miller James G.
Published: July 2007

The objective of this investigation is to introduce and validate a practical ultrasound source to be used in the investigation of the nonlinear material properties of liquids and soft tissues studied in vitro. Methods based on the progressive distortion of finite amplitude ultrasonic waves in the low megahertz frequency range are most easily implemented under the assumption of plane wave propagation. However, achieving an approximately planar ultrasonic field over substantial propagation distances can be challenging. Furthermore, undesired harmonic distortion of the ultrasonic field prior to insonification of the specified region of interest represents another serious limitation. This paper introduces an approach based on the use of the ultrasonic field emanating from a stainless-steel delay line. Both simulation and direct experimental measurement demonstrate that such a field exhibits relatively planar wave fronts to a good approximation (such that a 3-mm-diam receiver would be exposed to no more than 3dB of loss across its face) and is free from the significant harmonic distortion that would occur in a conventional water path.
Comparison of biomechanical modeling of register transitions and voice instabilities with excised larynx experiments
Authors: Tokuda Isao T. , Horáček Jaromir , Švec Jan G. , Herzel Hanspeter
Published: July 2007

Voice instabilities were studied using excised human larynx experiments and biomechanical modeling. With a controlled elongation of the vocal folds, the experiments showed registers with chest-like and falsetto-like vibrations. Observed instabilities included abrupt jumps between the two registers exhibiting hysteresis, aphonic episodes, subharmonics, and chaos near the register transitions. In order to model these phenomena, a three-mass model was constructed by adding a third mass on top of the simplified two-mass model. Simulation studies showed that the three-mass model can vibrate in both chest-like and falsetto-like patterns. Variation of tension parameters which mimic activities of laryngeal muscles could induce transitions between both registers. For reduced prephonatory areas and damping constants, extended coexistence of chest and falsetto registers was found, in agreement with experimental data. Subharmonics and deterministic chaos were observed close to transitions between the registers. It is concluded that the abrupt changes between chest and falsetto registers can be understood as shifts in dominance of eigenmodes of the vocal folds.
Underwater sound pressure variation and bottlenose dolphin (Tursiops truncatus) hearing thresholds in a small pool
Authors: Finneran James J. , Schlundt Carolyn E.
Published: July 2007

Studies of underwater hearing are often hampered by the behavior of sound waves in small experimental tanks. At lower frequencies, tank dimensions are often not sufficient for free field conditions, resulting in large spatial variations of sound pressure. These effects may be mitigated somewhat by increasing the frequency bandwidth of the sound stimulus, so effects of multipath interference average out over many frequencies. In this study, acoustic fields and bottlenose dolphin (Tursiops truncatus) hearing thresholds were compared for pure tone and frequency modulated signals. Experiments were conducted in a vinyl-walled, seawater-filled pool approximately 3.7×6×1.5m. Acoustic signals were pure tone and linear and sinusoidal frequency modulated tones with bandwidths/modulation depths of 1%, 2%, 5%, 10%, and 20%. Thirteen center frequencies were tested between 1 and 100kHz. Acoustic fields were measured (without the dolphin present) at three water depths over a 60×65cm grid with a 5-cm spacing. Hearing thresholds were measured using a behavioral response paradigm and up/down staircase technique. The use of FM signals significantly improved the sound field without substantially affecting the measured hearing thresholds.
Overexposure effects of a 1-kHz tone on the distortion product otoacoustic emission in humans
Authors: Reuter Karen , Ordoñez Rodrigo , Hammershøi Dorte
Published: July 2007

The effects of overexposure on the properties of distortion product otoacoustic emissions (DPOAEs) are investigated. In total, 39 normal-hearing humans were monaurally exposed to a 1-kHz tone lasting for 3min at an equivalent threshold sound-pressure level of 105.5dB. The effects of overexposure were studied in two experiments (1) on the broadband DPOAE and (2) on the DPOAE fine structure, measured using a higher frequency resolution in a narrower frequency range. The obtained DPOAE shifts were compared to temporary threshold shift (TTS) obtained after a similar exposure. Similarities between DPOAE shifts and TTS were found in the affected frequency range and the time course of recovery. The amount of TTS was higher in the early recovery time (1–4-min postexposure), but similar to the DPOAE shift (even in absolute terms) at later recovery times (5–20-min postexposure). The DPOAE fine structure was not systematically changed after the exposure.
Response to Comment on "The Spatial Extent of 20th-Century Warmth in the Context of the Past 1200 Years"
Authors: Osborn Timothy J. , Briffa Keith R.
Published: July 2007

Reconsidering the basis for selecting proxy records according to their correlation with local temperature has no substantive influence on the statistical significance of 20th-century warming that we reported, provided that the degree of selectivity is correctly estimated. The conclusion that recent warming is unusually widespread compared with the past 1200 years therefore remains valid.
Label-Free, Single-Molecule Detection with Optical Microcavities
Authors: Armani Andrea M. , Kulkarni Rajan P. , Fraser Scott E. , Flagan Richard C. , Vahala Kerry J.
Published: July 2007

Current single-molecule detection techniques require labeling the target molecule. We report a highly specific and sensitive optical sensor based on an ultrahigh quality (
Q
) factor (
Q
> 10
8
) whispering-gallery microcavity. The silica surface is functionalized to bind the target molecule; binding is detected by a resonant wavelength shift. Single-molecule detection is confirmed by observation of single-molecule binding events that shift the resonant frequency, as well as by the statistics for these shifts over many binding events. These shifts result from a thermo-optic mechanism. Additionally, label-free, single-molecule detection of interleukin-2 was demonstrated in serum. These experiments demonstrate a dynamic range of 10
12
in concentration, establishing the microcavity as a sensitive and versatile detector.
Plant Hormone Signaling Receptor
Authors: Hines Pamela J.
Published: July 2007

The hormone abscisic acid (ABA) regulates a variety of developmental and physiological processes in higher plants. Liu
et al
. (see the Perspective by Grill and Christmann) have now identified a membrane-bound protein that functions as an ABA receptor. The protein, GCR2, has features of a G protein-coupled receptor, which has thousands of variants in animal cells but very few known variants in plant cells.

X. Liu, Y. Yue, B. Li, Y. Nie, W. Li, W.-H. Wu, L. Ma, A G protein-coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid.
Science
315
, 1712-1716 (2007).
[Abstract]
[Full Text]

E. Grill, A. Christmann, A plant receptor with a big family.
Science
315
, 1676-1677 (2007).
[Summary]
[Full Text]
Calpain Cleaves a Memory Inhibitor
Authors: Gough Nancy R.
Published: July 2007

Calpain, a calcium-dependent protease, has been implicated in neuronal responses to various stimuli, and Shimizu
et al
. provide evidence that calpain contributes to certain types of learning and memory. Shimizu
et al
. (see commentary by Bolshakov) found that suprachiasmatic nucleus circadian oscillatory protein (SCOP) was abundant in the hippocampus of mice and rats. Overexpression of SCOP in cultured hippocampal neurons decreased the expression of an adenosine 3′,5′-monophosphate (cAMP) response element (CRE)-regulated reporter gene stimulated by brain-derived neurotrophic factor (BDNF), whereas knockdown of the endogenous protein using RNA interference enhanced reporter gene expression in the presence or absence of BDNF. CRE-mediated gene expression is downstream of activation of mitogen-activated protein kinases (MAPKs) and contributes to synaptic changes involved in learning and memory. SCOP was previously reported to inhibit K-Ras by sequestering the nucleotide-free form, thereby inhibiting MAPK activation. The authors found that SCOP abundance was decreased in cultured hippocampal neurons stimulated with BDNF, the glutamate receptor agonist NMDA, or KCl. Assays for SCOP cleavage in cell-free extracts in the presence of various protease pharmacological inhibitors indicated that calpains, not caspase 3 or the proteasome, cleaved SCOP and that SCOP cleavage required calcium. In cultured hippocampal neurons, calpain inhibition blocked SCOP degradation and decreased the phosphorylation (and activation) of the MAPK ERK-2 stimulated by BDNF. In mice, memory for new objects was associated with a decrease in the abundance of SCOP (in whole hippocampal extracts). Mice overexpressing SCOP using an inducible promoter showed decreased memory for new objects 24 hours after object training but no deficiency in short-term memory. Consistent with a role for calpain in memory, administration of a calpain inhibitor into the hippocampus blocked new object memory after 24 hours but had no effect on short-term memory measured after 8 minutes.

K. Shimizu, T. Phan, I. M. Mansuy, D. R. Storm, Proteolytic degradation of SCOP in the hippocampus contributes to activation of MAP kinase and memory.
Cell
128
, 1219-1229 (2007).
[Online Journal]

V. Y. Bolshakov, SCOPing out proteases in long-term memory.
Cell
128
, 1029-1030 (2007).
[Online Journal]
Those Anxious Adolescents
Authors: Gough Nancy R.
Published: July 2007

Why are teenagers so prone to moodiness and melodrama? Research by Shen
et al
. on mice suggests that neurosteroids, which potentiate γ-aminobutyric acid (GABA)-mediated chloride conductance and are antianxiety agents in adults, actually act to promote excitability and stimulate anxiety during puberty. Shen
et al
. found that the neurosteroid known as THP (3α-OH-5α[β]-pregnan-20-one) decreased, rather than increased, chloride conductance through a specific GABA receptor composed of α4β2δ subunits when this receptor was expressed in human embryonic kidney (HEK) 293 cells. In female mice, the abundance of the α4 and δ subunits, which were determined as critical for this reversed effect of THP, increased at the onset of puberty, whereas these subunits were barely detectable in prepubertal and adult animals. Electrophysiological recordings of hippocampal slices of pubertal mice confirmed that THP reduced GABA-mediated tonic inhibitory current and increased neuronal excitability, which is consistent with these GABA receptors serving as extrasynaptic tonic inhibitors of neural activity. In contrast, THP increased tonic current and neuronal excitability before puberty or in mice in which the δ subunit was knocked out. In vivo, administration of THP to pubertal mice or induction of stress, which raises endogenous production of THP, increased anxiety, measured as a reduction in the time spent in the open arm of an elevated maze. This was in contrast to the behavior of prepubertal and adult mice in which THP increased time spent in the open arm, representing an anxiolytic effect. Inhibition of THP production prevented the pro- or antianxiety effects of previous exposure to stress, thus confirming that in adults and adolescents THP is produced in response to stress despite causing opposite behavioral responses. In adult animals, withdrawal of THP stimulates the appearance of α4 and δ subunits. At the onset of puberty, THP declined, and administration of THP to the pubertal mice prevented the increase in α4 and δ subunits, thus confirming that THP also controls GABA receptor composition in both adult and adolescent mice. Thus, THP appears to be one of the keys to controlling anxiety and understanding adolescent behavior. The implications of this research for teenagers are discussed by McCarthy.

H. Shen, Q. H. Gong, C. Aoki, M. Yuan, Y. Ruderman, M. Dattilo, K. Williams, S. S. Smith, Reversal of neurosteroid effects at α4β2δ GABA
A
receptors triggers anxiety at puberty.
Nat. Neurosci.
10
, 469-477 (2007).
[PubMed]

M. M. McCarthy, GABA receptors make teens resistant to input.
Nat. Neurosci.
10
, 397-399 (2007).
[PubMed]
Receptors Respond to Metabolic Flux
Authors: Gough Nancy R.
Published: July 2007

Many cell surface proteins, including receptors, are N-glycosylated as they transit through the biosynthetic pathway. Proteins containing branched structures with poly-N-acetyllactosamine show a higher affinity for galectins, cell-surface proteins that bind glycosylated proteins, than proteins with less branched structures. The galectin interaction appears to limit endocytosis of the receptors. The formation of branched structures requires the intermediate formed by the activity of N-acetylglycosaminyltransferase V (Mgat5), which is dependent on the concentration of UDP-N-acetylglucosamine (UDP-GlcNAc), a product of the hexosamine pathway. Lau
et al
. combined mathematical modeling of glycosylation branching and the effects of this on the cell-surface expression and signaling of various types of receptors. They found that supplementation of
Mgat5
–/–
cells with GlcNAc increased the interaction of epidermal growth factor receptors (EGFRs) and transforming growth factor-β receptors (TGFβRs) with galectin and increased their abundance at the cell surface. Surprisingly, the EGFR with eight N-glycosylation sites showed a hyberbolic increase in responsiveness (phosphorylation of its downstream effector ERK), whereas TGFβR (with only one or two glycosylation sites) showed a sigmoid or switchlike increase in responsiveness (nuclear translocation of its downstream effector Smad proteins) when the
Mgat5
–/–
cells were supplemented with increasing concentrations of GlcNAc. Based on this observation, the authors were able to create a mathematical model that described the dependency of cell surface protein abundance on glycosylation state and metabolic flux through the hexosamine pathway. Receptors that promote proliferation generally have higher numbers of glycosylation sites than those that promote growth arrest and differentiation, and these proliferation-inducing receptors show a hyperbolic increase in responsiveness to increased flux through the hexosamine pathway. Modeling suggested that the switch-like behavior of the growth-arresting receptors allows them to be ultrasensitive to metabolic state. Stanley discusses the implications and next steps for testing this model.

K. S. Lau, E. A. Partridge, A. Grigorian, C. I. Silvescu, V. N. Reinhold, M. Demetriou, J. W. Dennis, Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation.
Cell
129
, 123-134 (2007).
[Online Journal]

P. Stanley, A method to the madness of N-glycan complexity?
Cell
129
, 27-29 (2007).
[Online Journal]
The Mechanism of Action of the Tumor Suppressor HRSL3
Authors: Foley John F.
Published: July 2007

Loss of tumor suppressor function is a critical step in the development of tumors. Two classes of tumor suppressors are known. Loss of function of class I suppressors, such as p53, is achieved through genetic alterations, whereas inhibition of class II suppressors is reversible and leaves their genomic structures unchanged. Nazarenko
et al
. investigated the mechanism of action of the class II suppressor HRSL3. HRSL3 protein is found in normal tissues but is undetectable in human tumors. The authors performed a yeast two-hybrid screen for binding partners for HRSL3 and detected PR65α, the regulatory subunit Aα of protein phosphatase 2A (PP2A), a serine/threonine phosphatase. Using HRSL3 mutants, the authors determined that the N-terminal region of HRSL3 was necessary for binding to PR65α. Coimmunoprecipitation studies in a transfected human ovarian carcinoma cell line (OVCAR-3) demonstrated that HRSL3 did not bind to the catalytic subunit of PP2A, PR36α. The catalytic activity of PP2A isolated from cells that contained HRSL3 was much reduced compared with that of PP2A isolated from cells that contained a noninteracting mutant of HRSL3. Through flow cytometric analysis of nuclear DNA and Western blotting analysis, the authors demonstrated that either increased amounts of HRSL3 or knockdown of PP2A with a PR65-specific siRNA induced apoptosis of OVCAR-3 cells. The presence of HRSL3 in OVCAR-3 cells resulted in increased amounts of phosphorylated PKCζ, a target of PP2A. Blocking PKCζ activity with a pseudosubstrate peptide abrogated HRSL3-induced apoptosis of the OVCAR-3 cells, suggesting a role for PKCζ in regulating cell death in ovarian cancer.

I. Nazarenko, R. Schäfer, C. Sers, Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells.
J. Cell. Sci.
120
, 1393-1404 (2007).
[Abstract]
[Full Text]
Inhibition of IL-13 Signaling in Bronchial Epithelial Cells by LPA
Authors: Foley John F.
Published: July 2007

The cytokine interleukin-13 (IL-13), a Th2-associated cytokine, plays a role in the pathogenesis of bronchial asthma. IL-13 signals through its receptor, a heterodimer of IL-13 receptor α1 (IL-13Rα1) and IL-4 receptor α (IL-4Rα), to activate signal transducer and activator of transcription 6 (STAT6). Another receptor, IL-13Rα2, with higher affinity for IL-13 than that of IL-13Rα1, acts as a decoy receptor for IL-13, blocking its signaling. Phospholipid lysophosphatidic acid (LPA) has been detected in the lung and signals through G protein-coupled receptors to enhance production of epithelial chemokines. To investigate a role for LPA in airway modulation, Zhao
et al
. treated primary cultures of human bronchial epithelial cells (HBEpCs) with LPA for various time periods. Through real-time polymerase chain reaction and Western blotting analyses, the authors found that the abundance of mRNA and protein for IL-13Rα2, but not IL-13Rα1 or IL-4Rα, were increased and that IL-13Rα2 protein was secreted by the cells, with a peak production time after 6 hours of treatment. These effects were blocked if cells were pretreated with pertussis toxin, indicating that the effect of LPA on IL-13Rα2 production was mediated by G proteins of the G
i
family. Treatment of HBEpCs with LPA also blocked the ability of IL-13, but not IL-4, to activate STAT6. Studies with pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that LPA stimulation of IL-13Rα2 production was dependent on the activities of both c-Jun N-terminal kinase and phospholipase D. This study suggests that LPA functions to protect bronchial epithelium during airway inflammation in asthma.

Y. Zhao, D. He, J. Zhao, L. Wang, A. R. Leff, E. W. Spannhake, S. Georas, V. Natarajan, Lysophosphatidic acid induces interleukin-13 (IL-13) receptor α2 expression and inhibits IL-13 signaling in primary human bronchial epithelial cells.
J. Biol. Chem.
282
, 10172-10179 (2007).
[Abstract]
[Full Text]