bluuebunny/crossref_metadata_2025 huggingface dataset:
Boron neutron capture therapy (BNCT): Implications of neutron beam and boron compound characteristics
Authors: Wheeler Floyd J. , Nigg David W. , Capala Jacek , Watkins Peter R. D. , Vroegindeweij Corine , Auterinen Iiro , Seppälä Tiina , Bleuel Darren
Published: July 2002

The potential efficacy of boron neutron capture therapy (BNCT) for malignant glioma is a significant function of epithermal‐neutron beam biophysical characteristics as well as boron compound biodistribution characteristics. Monte Carlo analyses were performed to evaluate the relative significance of these factors on theoretical tumor control using a standard model. The existing, well‐characterized epithermal‐neutron sources at the Brookhaven Medical Research Reactor (BMRR), the Petten High Flux Reactor (HFR), and the Finnish Research Reactor (FiR‐1) were compared. Results for a realistic accelerator design by the E. O. Lawrence Berkeley National Laboratory (LBL) are also compared. Also the characteristics of the compound p‐Boronophenylaline Fructose (BPA‐F) and a hypothetical next‐generation compound were used in a comparison of the BMRR and a hypothetical improved reactor. All components of dose induced by an external epithermal‐neutron beam fall off quite rapidly with depth in tissue. Delivery of dose to greater depths is limited by the healthy‐tissue tolerance and a reduction in the hydrogen‐recoil and incident gamma dose allow for longer irradiation and greater dose at a depth. Dose at depth can also be increased with a beam that has higher neutron energy (without too high a recoil dose) and a more forward peaked angular distribution. Of the existing facilities, the FiR‐1 beam has the better quality (lower hydrogen‐recoil and incident gamma dose) and a penetrating neutron spectrum and was found to deliver a higher value of Tumor Control Probability (TCP) than other existing beams at shallow depth. The greater forwardness and penetration of the HFR the FiR‐1 at greater depths. The hypothetical reactor and accelerator beams outperform at both shallow and greater depths. In all cases, the hypothetical compound provides a significant improvement in efficacy but it is shown that the full benefit of improved compound is not realized until the neutron beam is fully optimized.
Dose measurements compared with Monte Carlo simulations of narrow 6 MV multileaf collimator shaped photon beams
Authors: De Vlamynck K. , Palmans H. , Verhaegen F. , De Wagter C. , De Neve W. , Thierens H.
Published: July 2002

Small fields where electronic equilibrium is not achieved are becoming increasingly important in clinical practice. These complex situations give rise to problems and inaccuracies in both dosimetry and analytical/empirical dose calculation, and therefore require other than conventional methods. A natural diamond detector and a Markus parallel plate ionization chamber have been selected for clinical dosimetry in 6 MV photon beams. Results of simulations using the Monte Carlo system BEAM/EGS4 to model the beam geometry have been compared with dose measurements. A modification of the existing component module for multileaf collimators (MLCs) allowed the modeling of a linear accelerator SL 25 (Elekta Oncology Systems) equipped with a MLC with curved leaf‐ends. A mechanical measurement method with spacer plates and a light‐field edge detection technique are described as methods to obtain geometrical data of collimator openings for application in the Monte Carlo system. Generally a good agreement is found between measurements and calculations of depth dose distributions and deviations are typically less than 1%. Calculated lateral dose profiles slightly exceed measured dose distributions near the higher level of the penumbras for a field, but agree well with the measurements for all other cases. The simulations are also able to predict variations of output factors and ratios of output factors as a function of field width and field‐offset. The Monte Carlo results demonstrate that qualitative changes in energy spectra are too small to explain these variations and that especially geometrical factors affect the output factors and depth dose curves and profiles.
Nonlinear dynamics: A tutorial on the method of normal forms
Authors: Kahn Peter B. , Zarmi Yair
Published: July 2002

We consider a variety of nonlinear systems, described by linear differential equations, subjected to small nonlinear perturbations. Approximate solutions are sought in terms of expansions in a small parameter. The method of normal forms is developed and shown to be capable of constructing a series expansion in which the individual terms in the series correctly incorporate the essential aspects of the full solution. After an extensive introduction, we discuss a series of examples. Most of our attention is given to autonomous systems with imaginary eigenvalues for the unperturbed problem. But, we also analyze a system of equations with negative eigenvalues; one zero and one negative eigenvalue; two nonautonomous problems and phase locking in a coupled-oscillator system. We conclude with a brief section on an integral formulation of the method.
The Ewald–Oseen extinction theorem and extinction lengths
Authors: Ballenegger Vincent C. , Weber T. A.
Published: July 2002

We give an elementary demonstration of the extinction theorem for electromagnetic waves at normal incidence on a plane surface of a medium. We stress that the extinction of the incident wave and its replacement with a wave of index of refraction n takes place throughout the medium rather than in the surface layers. Although the extinction theorem is usually thought to apply only to dielectrics, we extend the theorem to include conductors. We use the macroscopic fields in which the contributions of the oscillating dipoles in a dielectric or the induced currents in a conductor are already summed. Our elementary derivation of the extinction theorem should be readily accessible to advanced undergraduates since it depends only on the superposition principle and the solution of the wave equation. An analogy is made between this extinction and the cancellation of the electric field inside a conductor placed in a static electric field. We also study the more advanced case of propagation of radiation in a dilute random medium in which the wavelength is small relative to the interparticle distance and find that an analogous extinction of the incident wave takes place. Furthermore, for the dilute random medium, we estimate the length into the medium for which a large fraction, (1−1/e), of the incident radiation has interacted with the particles making up the medium. This length is much larger than any lengths associated with the extinction theorem itself.
Interference from degraded auditory stimuli: Linear effects of changing-state in the irrelevant sequence
Authors: Jones Dylan M. , Alford David , Macken William J. , Banbury Simon P. , Tremblay Sébastien
Published: July 2002

Cognitive performance, particularly on a number of tasks involving short-term memory for order, is impaired by the mere presence of irrelevant background sound. The current study examines the features of the irrelevant sound that determine its disruptive potency. Previous research suggests that the amount of variability in an irrelevant stream is related to the degree of disruption of memory. The present experiments used a parametric approach to manipulate degree of change more precisely. Increasing levels of degradation, effected either by low-pass filtering (speech) or by digital manipulation (speech and nonspeech), monotonically decreased the degree of interference. The findings support the following propositions: (i) the degree of physical change within an auditory stream is the primary determinant of the degree of disruption; and, (ii) the effects of irrelevant speech and irrelevant nonspeech sounds are functionally similar.
Fluctuations of spherical waves in a turbulent atmosphere: effect of the axisymmetric approximation in computational methods
Authors: Salomons Erik M.
Published: July 2002

The validity of the axisymmetric parabolic-equation (PE) method for line-of-sight sound propagation in a turbulent atmosphere is investigated. The axisymmetric PE method is a finite-difference method for solving a 2D parabolic wave equation, which follows from the 3D wave equation by the assumption of axial symmetry around the vertical axis through the source. It is found that this axisymmetric approximation has a considerable spurious effect on the fluctuations of the sound field. This is concluded from analytical expressions for the log-amplitude and phase variances, derived both for isotropic turbulence and for axisymmetric turbulence. The expressions for axisymmetric turbulence are compared with the results of numerical computations with the PE method.
Modeling of high-frequency scattering from objects using a hybrid Kirchhoff/diffraction approach
Authors: Fawcett J. A.
Published: July 2002

In this paper a numerical discretization and transformation into the time domain of a hybrid Kirchhoff/diffraction method is presented for the modeling of high-frequency pulse scattering from rigid bodies. A series of benchmark cases, for smooth and rough spheres and cylinders, is presented to establish the accuracy of the method in the time domain.
Broadband parametric imaging of breaking ocean waves
Authors: Andrew Rex K. , Farmer David M. , Kirlin R. Lynn
Published: July 2002

An acoustic array was deployed in the near-surface layer of a fetch-limited coastal inlet to image breaking waves using only the sound radiated in the band (400 Hz to 2000 Hz) from the breaking region. The breakers were assumed to possess predominantly spiller characteristics. For this frequency band, the wavelength of sound in bubble-free water is much larger than the surface wave height and the depth of the breaker bubble plume, so both were considered insignificant. The 15-element array was configured as a sparse horizontal cross with an 8 m aperture, bottom moored, and positioned nominally 3 m beneath the surface. Propagation from the source to the array elements assumed dipole sources, an acoustically flat surface, and an acoustically thin bubble plume. The radiating region was parameterized by a broadband two-dimensional Gaussian profile: information from up to six independent frequencies was combined to yield a maximum-likelihood image. Analysis shows that the images align closely with the wind and can be observed moving downwind with a speed roughly equal to 70% of the phase speed of the dominant wind waves. A model of acoustic source strength which is linear in log frequency is found fit the data reasonably well, and model parameters are provided for a single wind speed. Unlike other imaging experiments, this technique provides measurements of the size and shape of the bubble-creation region at or near the peak of the radiated autospectrum.
Articulation index predictions for hearing-impaired listeners with and without cochlear dead regions
Authors: Rankovic Christine M.
Published: July 2002

Vickers, Moore, and Baer [J. Acoust. Soc. Am. 110, 1164–1175 (2001)] reported that hearing-impaired subjects with cochlear “dead regions” benefited from amplification of frequencies up to an octave above the estimated edge frequency of the dead region, but not beyond, whereas hearing-impaired subjects without dead regions did show benefit beyond this boundary. Dead regions are thought to have no functioning inner hair cells. Vickers et al. indicated that a clinical test for detecting dead regions would provide supplementary information that is important for hearing aid fitting. Furthermore, they suggested that the articulation index (AI) may overestimate the potential benefit of amplification for listeners with dead regions because the AI does not account for the presence of dead regions. To evaluate their claims, we conducted an AI analysis [H. Fletcher, Speech and Hearing in Communication (Van Nostrand, New York, 1953); H. Fletcher and R. H. Galt, J. Acoust. Soc. Am. 22, 89–151 (1950)]. Results show that the AI is generally accurate in predicting the consonant recognition test scores of Vickers et al.’s subjects irrespective of the presence/absence of dead regions. This suggests that audiogram differences account for the observed performance differences; it was not necessary to invoke dead regions to explain the speech test results. The results of the AI analysis are sufficiently accurate to call in to question whether a clinical test for dead regions would offer additional predictive information.
The relationship between localization and the Franssen effect
Authors: Yost William A. , Mapes-Riordan Dan , Guzman Sandra J.
Published: July 2002

The relationship between localization and the Franssen effect was studied for noise and tones in a sound-deadened and in a live room. The noise was wideband and the tones were 250, 500, 1000, 1500, 2500, and 4000 Hz. Listeners were asked to determine the location of the stimuli in a localization task and to discriminate the difference between a pair of stimuli used to generate the Franssen illusion and a steady-state tone in a Franssen-effect discrimination task. Poor performance in the Franssen-effect discrimination task is consistent with the stimulus conditions leading to a strong Franssen illusion. Poor performance in both the Franssen effect and localization tasks was obtained for midfrequency tones (near 1500 Hz) and in the live room. Thus, the Franssen illusion is strongest for a live room and for midfrequency tones consistent with the difficulty listeners have in localizing sounds under these conditions. These results are consistent with those of Hartmann and Rakerd [J. Acoust. Soc. Am. 86, 1366–1373 (1989)] and support their suggestion of a correlation between the Franssen effect and localization in rooms.
Measurements of small-caliber ballistic shock waves in air
Authors: Stoughton Roland
Published: July 2002

Megahertz bandwidth pressure measurements of airborne ballistic shock waves from bullets are presented which confirm weak-shock theoretical predictions of waveform shape, period, amplitude, and the scaling of these quantities with shock propagation distance. Wavefront distortions and amplitude variations are quantified versus shock propagation distances of 3–55 m and agree with predictions based on linear acoustic propagation through simple turbulence models. Observed rise times probably exhibit a mix of turbulence and molecular relaxation effects.
TV holography measurements of underwater acoustic fields
Authors: Rustad Rolf , Lo/kberg Ole Johan , Pedersen Hans Magne , Klepsvik Kristin , Sto/ren Trude
Published: July 2002

Members of our group have previously demonstrated that TV holography may be used to measure the amplitude and the phase distributions of a sound field in air. This technique is not limited to acoustic fields in air, but may be applied to acoustic fields in any transparent medium. Its applicability to ultrasonic fields in water is demonstrated in this Letter.
The domain of phrase-final lengthening in English
Authors: Shattuck-Hufnagel Stefanie , Turk Alice
Published: July 2002

Intonational phrase final lengthening is well established for the final syllable rhyme in English [Klatt (1976), Wightman (1992), Campbell and Isard (1991)]; there is some evidence for lengthening extending further leftward [Langeveld (1997) for Dutch, Berkowitz (1993) for Hebrew], and for post-boundary lengthening of the initial consonant of a new prosodic constituent [Fougeron and Keating (1997), Fougeron (1997), Gow and Gordon (1995), and A. Cooper (1991)]. It is asked whether boundary-related duration lengthening extends further in both directions from a prosodic constituent boundary, using prosodically disambiguated sentence pairs like ‘‘Please say ‘Thomasburg or Terraceville and Watertown will play’ ’’ and ‘‘Please say ‘Michigan or Madison and Vatican will play,’ ’’ in which pitch-accent and main-word-stress-related lengthening can be distinguished from boundary-related lengthening. Results will be presented for 40 sentence pairs produced by four speakers (normal and reiterant forms) for individual time segments measured across the full extent of each target phrase. Preliminary results from a single speaker suggest that preboundary lengthening can extend leftward to the primary stress of a polysyllabic word. [Work supported by EPSRC.]
When bad amplification is good: Distortion as an artistic tool for guitar players
Authors: Zwicker Tilmann , Buus So/ren
Published: July 2002

This presentation surveys the development of and the approaches to distortion for electric guitars, which plays an extremely important role in modern popular music, particularly in Rock, Blues, Jazz, and Pop. The signal processing for guitar amplification has always included nonlinear effects that are usually heard as distortion, but also lends other important characteristics to the guitar tone. Originally, distortion occurred as musicians tried to coax more volume out of their amplifiers than they were designed to deliver. However, this ‘‘design flaw’’ soon became a tremendous asset. Guitarists discovered that, if handled properly, distortion gave their instruments an expressive, harmonically rich, and highly controllable voice rivaling that of horn players. Today, distortion for electric guitars has been cultivated to the extent that it is deliberately designed into every guitar amplifier. Characteristics of electric-guitar signals and distortion devices will be discussed and illustrated with examples. The reasons why distortion is a desirable artistic tool and related psychoacoustic aspects also will be discussed.
Perception of glottalized consonants in Babine/Witsuwit’en
Authors: Davis Katharine , Hargus Sharon
Published: July 2002

Previous studies of Babine/Witsuwit’en have shown speaker differences in the production of glottalized stops [Davis and Hargus, J. Acoust. Soc. Am. 100, 2690 (1996)]. The present study investigates native listeners’ perception of the glottal/nonglottal contrast. Ten subjects were presented with 16 naturally produced minimal pairs contrasting glottalized and voiceless unaspirated stops or affricates. These tokens, interspersed with 18 control minimal pairs, were presented in random order. Listeners’ judgments were recorded on a forced-choice answer sheet. The task was performed twice, once with a male voice and once with a female voice. Subjects showed greater confusion when identifying members of the glottal/nonglottal contrast than when identifying members of the control contrasts (84% correct versus 93% correct). Among control items, voiceless unaspirated and voiceless aspirated pairs were correctly distinguished 97% of the time. ANOVA results considering all experimental factors (subject, speaker, place of articulation, etc.) will be presented. In addition, acoustic analyses of correctly identified versus confused glottal/nonglottal pairs will be presented. Particular attention will be paid to significant factors (VOT, F0) from earlier production studies.
Thermal analysis of high drive transducer elements
Authors: Montgomery Robert , Butler Stephen C.
Published: July 2002

The increasing demand for high-power, low-cost, compact transducer packages for underwater acoustic applications is leading to concerns of overheating in the active driving piezoelectric ceramic (lead zirconate titanate) elements and the associated passive materials (epoxies and polyurethanes). Pushing a design to its thermal limits can lead to reduced acoustic performance and reliability. There is not much guidance to be found in the literature that provides an analytical approach to cope with thermal issues of piezoelectric ceramics in the design phase. An analytic modeling effort is presented that addresses the thermal issues for compact high drive 31-mode free-flooded ring underwater sonar transducers. In this particular case, the thermal issues proved to be the limiting design concerns over the field and stress-limited cases. However, with modeling (analytical and finite element) and bench testing of components, the proper choice of materials and configuration parameters were determined and the performance goals were subsequently achieved. The approach addresses both the transient thermal response and the steady-state temperature profile that results from high-power, high duty cycle drive. These results may prove useful for other similar designs. [Work supported by ONR.]
Calculated coherence and extinction of sound waves propagating through anisotropic, shear-induced turbulent velocity fluctuations
Authors: Wilson D. Keith
Published: July 2002

Previous calculations of the coherence and extinction of sound waves propagating through turbulence have almost always used isotropic models for the turbulence. However, low-frequency sound waves are strongly affected by energy-subrange turbulence structure, which is anisotropic by nature. In this paper, coherence and extinction are calculated using several anisotropic models for turbulent velocity fluctuations in the neutral atmospheric shear layer. New anisotropic versions of the Gaussian and von Kármán models are developed. The Kristensen et al. spectral model [Boundary-Layer Meteorol. 47, 149–193 (1989)] and Mann’s rapid-distortion, constant shear model [J. Fluid Mech. 273, 141–168 (1994)] are also considered. The turbulence models all predict that the crosswind extinction distance is longer than the along-wind value, although they disagree as to the extent of the lengthening: depending on the model, the ratio of crosswind to along-wind extinction varies from 2.1 to 13. These results point to the need for good experiments. Similarly, coherence of the propagating wavefronts is predicted to persist over longer distances in the crosswind direction.
Lamb wave characterization of the effects of long-term thermal-mechanical aging on composite stiffness
Authors: Seale Michael D. , Madaras Eric I.
Published: July 2002

Lamb waves offer a promising method of evaluating damage in composite materials. The Lamb wave velocity is directly related to the material parameters, so an effective tool exists to monitor damage in composites by measuring the velocity of these waves. The Lamb Wave Imager™ (LWI) uses a pulse/receive technique that excites an antisymmetric Lamb mode and measures the time-of-flight over a wide frequency range. Given the material density and plate thickness, the bending and out-of-plane shear stiffnesses are calculated from a reconstruction of the dispersion curve. In this study, the time-of-flight as well as the elastic stiffnesses D11, D22, A44, and A55 for composite samples which have undergone combined thermal and mechanical aging are obtained. The samples examined include a baseline specimen with 0 cycles, specimens which have been aged 2350 and 3530 cycles at high strain levels, and one specimen aged 3530 cycles at low strain levels.
Differences in child and adult loudness judgments of rock music
Authors: Fucci Donald , Kabler Heather , Webster Debbie , McColl Doug
Published: July 2002

The present study was concerned with the perceptual processing of complex auditory stimuli in ten children (M_ age=8.1) as compared to ten young adults (M_ age=19.3) and ten older adult subjects (M_ age=54.2). The auditory stimulus used was 10 s of rock music [Led Zeppelin, CD Recording No. 19127−2 (Atlantic Recording Group, New York 1969)]. All three groups provided numerical responses to nine intensity levels of the rock music stimulus (10, 20, 30, 40, 50, 60, 70, 80, and 90 dB above threshold). Results showed that the children demonstrated a wider range of numerical responses than both adult groups. The range of mean numerical responses for the children was 0.54 to 54.24. For the young adults the range was 0.76 to 11.37, and for the older subjects it was 1.6 to 23.31. Results suggest that the children were not bound by the same set of rules as the adults in regard to magnitude estimation scaling of the loudness of the rock music stimulus. Their internal scaling mechanisms appeared to be more flexible and broader based than those of the adults who participated in this study.
Laser interrogation of the air–water interface for in-water sound detection: Initial feasibility tests
Authors: Antonelli Lynn T. , Walsh Kenneth M. , Alberg Andrew
Published: July 2002

Proof of concept experimentation recently demonstrated a new laser-based acoustic sonar technique to measure the velocity of the air-water interface using laser Doppler velocimeter technology. The laser acoustic sonar concept is unique since it directs laser light from the air onto the water surface. The light scattered from the interface contains Doppler information from which the boundary velocity is obtained. Data storage and signal processing can then be performed on the detected signal and the acoustic pressure in the water calculated from the measured velocity. The laser-based system presents an alternative means for broadband sonar reception that does not interfere with the water environment. Acoustic pressure signals as low as 119 dB relative to 1 μPa, between 2 and 50 kHz have been detected in the laboratory using the laser velocity sensor on a static water surface. The methods of implementing the laser acoustic velocity sensor to measure pressure fluctuations on a hydrodynamic interface were also explored in a high-velocity water tunnel [sponsored by the Office of Naval Research]. The results from the initial proof of concept experimentation from both the hydrostatic and hydrodynamic air–water interfaces is presented, demonstrating the feasibility of this sensor concept.
The mechanical waveform of the basilar membrane. II. From data to models—and back
Authors: de Boer Egbert , Nuttall Alfred L.
Published: July 2002

Mechanical responses in the basal turn of the guinea-pig cochlea are measured with low-level broad-band noise as the acoustical stimulus [for details see de Boer and Nuttall, J. Acoust. Soc. Am. 101, 3583–3592 (1997)]. Results are interpreted within the framework of a classical three-dimensional model of the cochlea that belongs to a very wide class of nonlinear models. The use of linear-systems analysis for this class of nonlinear models has been justified earlier [de Boer, Audit. Neurosci. 3, 377–388 (1997)]. The data are subjected to inverse analysis with the aim to recover the “effective basilar-membrane impedance.” This is a parameter function that, when inserted into the model, produces a model response, the “resynthesized” response, that is similar to the measured response. With present-day solution methods, resynthesis leads back to an almost perfect replica of the original response in the spatial domain. It is demonstrated in this paper that this also applies to the response in the frequency domain and in the time domain. This paper further reports details with regard to geometrical properties of the model employed. Two three-dimensional models are studied; one has its dimensions close to that of the real cochlea, the other is a stylized model which has homogeneous geometry over its length. In spite of the geometric differences the recovered impedance functions are very similar. An impedance function computed for one model can be used in resynthesis of the response in the other one, and this leads to global amplitude deviations between original and resynthesized response functions not exceeding 8 dB. Discrepancies are much larger (particularly in the phase) when a two-dimensional model is compared with a three-dimensional model. It is concluded that a stylized three-dimensional model with homogeneous geometric parameters will give sufficient information in further work on unraveling cochlear function via inverse analysis. In all cases of a sensitive cochlea stimulated by a signal with a stimulus level of 50 dB SPL per octave or less, the resulting basilar-membrane impedance is found to be locally active, that is, the impedance function shows a region where the basilar membrane is able to amplify acoustic power or to reduce dissipation of power by the organ of Corti. Finally, the influence of deliberate errors added to the data is discussed in order to judge the accuracy of the results.
Line spectral frequencies are poles and zeros of the glottal driving-point impedance of a discrete matched-impedance vocal tract model
Authors: Hasegawa-Johnson Mark
Published: July 2002

This correspondence demonstrates that the line spectral frequencies (LSFs) are the pole and zero frequencies of the glottal driving-point impedance of a discrete matched-impedance vocal-tract model. Several well-known characteristics of the LSFs, including the interlacing of pole and zero frequencies, are shown to follow naturally from this proof.
The role of the error model in the determination of the relaxation time spectrum
Authors: Elster C. , Honerkamp J.
Published: July 2002

The determination of the relaxation time spectrum from noisy experimental data is an ill-posed problem. Methods suitable for the treatment of such problems are regularization methods and maximum entropy methods. The solutions obtained thereby depend on the assumed errors of the given data. In order to obtain reliable results it is therefore necessary to test the correctness of the assumed error model. With the help of the well-known extension of the Shapiro and Wilk’s W test the proposed error model could be tested. The application of this test to synthetic data and experimental data from rheological measurements is investigated.
Linear viscoelastic properties of sucrose ester-stabilized oil-in-water emulsions
Authors: Guerrero A. , Partal P. , Gallegos C.
Published: July 2002

This paper deals with the influence of composition [sucrose ester SE and oil O concentrations] and temperature on the linear viscoelasticity properties of highly concentrated oil-in-water emulsions, using a hydrophilic sucrose palmitate as emulsifier. Different oil-in-water emulsions were prepared using a sucrose palmitate (SE=1–5 wt %) with a hydrophilic–lipophilic balance of 15, sunflower oil (O=60–80 wt %) and water. Oscillatory measurements were carried out in the linear viscoelasticity region. The relaxation time spectra of the emulsions were calculated using regularization techniques and were fitted to an empirical model proposed by Reference 1996. The results obtained are explained on the basis of the relationship among linear viscoelasticity properties, droplet size distribution, and characteristics of the continuous phase. Thus, an increase in sucrose palmitate concentration produces higher values of the linear viscoelasticity functions and a broader plateau region in the relaxation time spectrum, which suggests a certain enhancement of the elastic network.
ALPPL2‐Binding Peptide Facilitates Targeted mRNA Delivery for Efficient Hepatocellular Carcinoma Gene Therapy
Authors: Lei Sibei , Chen Xiaohua , Gao Yan , Shuai Ming , Zhou Weilin , Li Jingmei , Wu Jieping , Men Ke , Duan Xingmei
Published: August 2022

mRNA‐based gene therapy has emerged as an advanced strategy for hepatocellular carcinoma (HCC) treatment. However, one of its main limitations is lacking delivery precision in vivo. Distinguishing HCC cells from other tissues is crucial for maintaining the high stability, positive therapeutic outcomes, and safety of mRNA therapeutics. Here, a novel HCC specific peptide HCC167 is developed by phage display. It is shown that the HCC167 peptide can specifically recognize variety of HCC substrates including patient samples with high affinity. Modifying nanoparticles with the HCC167 peptide facilitates an effective HCC active targeting ability. When loading with Bims‐encoding mRNA, the systemically administrated DMP‐HCC167/Bims complex efficiently suppresses HCC progression in multiple models including patient‐derived xenografts. Furthermore, the ALPPL2 protein is identified as a specific binding receptor of the HCC167 peptide on the HCC cell membrane, uncovering a new active targeting mechanism based on the HCC167‐ALPPL2 ligand–receptor complex. The binding structure is also investigated by computer‐aided modeling. The study hence exhibits a potent active targeting strategy for mRNA‐based HCC therapy.
Controlling Charge Accumulation Properties of Organic Light‐Emitting Diodes using Dipolar Doping of Hole Transport Layers
Authors: Noguchi Yutaka , Hofmann Alexander , Brütting Wolfgang
Published: August 2022

It is demonstrated that dipolar doping of hole transport layers (HTLs) controls the density and polarity of the accumulated charge at the critical interface between the HTL and the emission layer (EML) in organic light‐emitting diodes (OLEDs). Dipolar doping enables spontaneous orientation polarization (SOP) even in nonpolar HTL, and consequently compensates for the negative interface charge originating from the SOP of the adjacent layer. This concept is applied to a phosphorescent OLED, where bis‐4(N‐carbazolyl)phenylphosphine oxide (BCPO) is employed as a polar dopant for the HTL. The net interface charge is completely compensated at ≈29.5% of doping and further doping even facilitates the positive interface charge. The luminescence loss due to triplet‐polaron quenching is observed for both hole and electron accumulations, and it is suppressed by reducing the net interface charge density. On the other hand, the carrier balance factor linearly decreases with increasing doping ratio of BCPO. The results suggest that besides the energy level offset, SOP and permanent dipole moment of the materials should also be taken into account for realizing efficient carrier blocking interfaces. Dipolar doping is a versatile tool to tune charge accumulation, and to study its influence on device performance as well as the role of SOP in OLEDs.
Real‐Time THz Beam Profiling and Monitoring via Flexible Vertically Aligned Carbon Nanotube Arrays
Authors: Xiao Dongyang , Wang Qian , Wang Zhaosong , Zhang Yili , Wu Jingbo , Fan Kebin , Sun Leimeng , Zhu Minmin , Ng Zhi Kai , Teo Edwin Hang Tong , Hu Fangjing
Published: August 2022

In terahertz (THz) quasi‐optical systems, the real‐time profiling and visualization of THz beams is of great importance for beam focusing and collimation applications. Herein, a cost‐effective and room‐temperature‐operated THz imaging device for this purpose is demonstrated experimentally using a flexible and broadband THz absorber based on a vertically aligned carbon nanotube (VACNT) array. Excellent THz absorption performances with an average power absorptance >96.8% are achieved within 0.1 and 2.5 THz. The energy of the incident THz wave is absorbed by the THz absorber and converted into heat that will re‐radiate and can be detected by an infrared (IR) camera as a result of the THz‐to‐IR conversion mechanism. Real‐time THz beam imaging and monitoring applications are demonstrated by a series of experiments at both 0.1 and 0.3 THz, providing an alternative approach for real‐time beam profiling and monitoring of THz waves.
De Novo Design of an Androgen Receptor DNA Binding Domain‐Targeted peptide PROTAC for Prostate Cancer Therapy
Authors: Ma Bohan , Fan Yizeng , Zhang Dize , Wei Yi , Jian Yanlin , Liu Donghua , Wang Zixi , Gao Yang , Ma Jian , Chen Yule , Xu Shan , Li Lei
Published: August 2022

Androgen receptor splice variant‐7 (AR‐V7), one of the major driving factors, is the most attractive drug target in castration‐resistant prostate cancer (CRPC). Currently, no available drugs efficiently target AR‐V7 in clinical practice. The DNA binding domain (DBD) is indispensable for the transcriptional activity of AR full length and AR splice variants, including AR‐V7. Based on the homodimerization structure of the AR DBD, a novel peptide‐based proteolysis‐targeting chimera (PROTAC) drug is designed to induce AR and AR‐V7 degradation in a DBD and MDM2‐dependent manner, without showing any activity on other hormone receptors. To overcome the short half‐life and poor cell penetrability of peptide PROTAC drugs, an ultrasmall gold (Au)‐peptide complex platform to deliver the AR DBD PROTAC in vivo is developed. The obtained Au‐AR pep‐PROTAC effectively degrades AR and AR‐V7 in prostate cancer cell lines, particularly in CWR22Rv1 cells with DC50 values 48.8 and 79.2 nM, respectively. Au‐AR pep‐PROTAC results in suppression of AR levels and induces tumor regression in both enzalutamide sensitive and resistant prostate cancer animal models. Further optimization of the Au‐AR pep‐PROTAC can ultimately lead to a new therapy for AR‐V7‐positive CRPC.
Preparation and evaluation of bismuth sulfide and magnetite‐based theranostic nanohybrid as drug carrier and dual MRI/CT contrast agent
Authors: Nosrati Hamed , Salehiabar Marziyeh , Mozafari Faezeh , Charmi Jalil , Erdoğan Nuri , Ghaffarlou Mohammadreza , Abhari Fatemeh , Danafar Hossein , Ramazani Ali , Nuri Ertas Yavuz
Published: August 2022

Due to the increased incidence and population growth that has been leading to growing number of cases worldwide, early diagnosis and treatment of cancer is crucial. Low density cancer tissue cannot be diagnosed before progressing toward a metastatic stage. Thus, theranostic systems play a significant role in assisting timely diagnosis and treatment. The combination of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents in a single probe is of high importance and necessity, where individual strengths of each approach can be merged while shortcomings of each modality could be compensated. With this motivation, we have developed and synthesized Bi2S3@BSA‐Fe3O4 nanoparticles as a dual MRI/CT contrast agent and carrier of curcumin (CUR) as natural anticancer drug. The nanoparticles shortened both the longitudinal (T1) and transverse (T2), MRI relaxation times, with a more distinct effect on producing negative contrast (T2) images with a relaxivity (r2) of 54.73 mM−1 s−1. The magnetite/bismuth hybrid nanoparticle also was capable of increasing CT image contrast. Further, in vitro cytotoxicity assay showed high biocompatibility of the synthesized nanoparticles. Furthermore, in vitro cytotoxicity assay on cancer cells showed high anticancer activity of the synthesized nanoparticles.
CpXCo(III)‐catalyzed selective C–H alkenylation of indoles with ethynylethylene carbonates
Authors: Niu Ruihan , Zhao Jiakai , Mou Qi , Zhao Ruyuan , Zhang Jing , Wang Meiqi , Sun Bo
Published: August 2022

An efficient and selective insertion of indoles into ethynylethylene carbonates has been achieved via CpXCo(III)‐catalyzed C–H functionalization. Compared with a Cp*Co(III) catalyst, the more sterically hindered CpXCo(III) improved the selectivity of rare 1,2‐insertion. This protocol provides an approach for synthesizing various vinylindoles in good yields with high regioselectivity.
Efficient and green one‐pot synthesis of Knoevenagel condensation catalyzed nano metal–organic frameworks in water
Authors: Mansouri Ghobad , Abdizad Mino , Abbasi Amir Reza , Rezayati Sobhan
Published: August 2022

Metal–organic frameworks (MOFs), Mlam‐NH‐66‐UiO and EtA‐NH‐66‐UiO, were prepared via post‐synthesis of the H2N‐66‐UiO and used as an efficient heterogeneous catalyst for Knoevenagel condensation of various aldehydes with malononitrile in water. The modified MOFs exhibited excellent catalyst activities in heterogeneous phase because of their large pore sizes and surface area, porosity, and the number of catalytically active sites (–NH2) on structures. In addition, the catalysts can be recycled and reused without decomposition of MOF structure and losing catalytic activity.
A unique experiment in undergraduate education in psychoanalysis: The Colorado College class at the Chicago Psychoanalytic Institute
Authors: Riker John H. , Dobson Marcia D.‐S.
Published: August 2022

In this paper we describe how we created an undergraduate course in psychoanalysis for Colorado College students at the Chicago Psychoanalytic Institute, how the course is constructed in terms of meeting with psychoanalysts, how we create an optimal ambiance for the course, how it is part of a psychoanalysis minor, and why it has been so meaningful for the students. We also articulate why we think teaching psychoanalysis to undergraduates is extraordinarily important and the difficulties and risks in doing so.
Apremilast exerts protective effects on stroke outcomes and blood–brain barrier (BBB) dysfunction through regulating Rho‐associated protein kinase 2 expression
Authors: Wang Mingyuan , Meng Xiangyuan , Cheng Zhihua
Published: August 2022

Aims

Stroke is a devastating event and a huge public health concern worldwide. Apremilast (APR) is a selective inhibitor of phosphodiesterase‐4 involved in various neurological diseases, including stroke. However, the protective effects of APR on stroke have not been investigated. Here, we explored the effects of APR on stroke outcomes and blood–brain barrier (BBB) dysfunction using a middle cerebral artery occlusion (MCAO) stroke mice model.

Results

The results show that APR attenuated neurological injury in MCAO mice with decreased neurological deficit scores and infarct size, as well as increased hanging grip time. The increased BBB permeability and decreased expression of the tight junction protein Claudin‐5 in MCAO mice were attenuated by APR treatment. APR treatment also mitigated neuroinflammation in MCAO mice, as shown by the decreased levels of inflammatory cytokines. In vitro assays also proved that APR ameliorated the oxygen/glucose deprivation/reoxygenation (OGD/R)‐induced increase in endothelial permeability and restored the expression of Claudin‐5 in bEnd.3 brain endothelial cells. Moreover, overexpression of ROCK2 in bEnd.3 cells abolished the protective effects of APR on endothelial permeability against OGD/R induction.

Conclusion

Taken together, our results demonstrate that APR showed significant efficacy on ischemic stroke outcomes by alleviating enhanced BBB permeability and neuroinflammation by inhibiting ROCK2. These findings suggest a novel therapeutic window for ischemic stroke.
The unintended consequences of remote work and a professional Zoom life
Authors: Zacarese Lawrence M.
Published: August 2022

A group of colleagues and I had just finished a meeting in a conference room last week when there was a knock at the door, and we received a message from a group of coworkers: “We have a meeting in here next.” As we gathered our folders and laptops to vacate the conference room, I was struck by the moment and realized how long it has been since I heard those words.
Make diversity, bias training a positive experience for your officers
Authors: Sutton Halley
Published: August 2022

LAS VEGAS — “This is a training about how to make diversity training and bias training palatable to law enforcement,” Lewis Eakins, Ph.D., CPP, Vice President for Public Safety and Emergency Management at Ivy Tech Community College in Indiana, said. Eakins spoke at the recent annual conference for the International Association of Campus Law Enforcement Administrators.
Polyurethane and polyurethane/hydroxyapatite scaffold in a three‐dimensional culture system
Authors: Ghasroldasht Mohammad M. , Mastrogiacomo Maddalena , Akbarian Fahimeh , Rezaeian Atefeh
Published: August 2022

Designing a new scaffold with an optimal ability of osteogenesis differentiation is a significant step bone tissue engineering along with the growing demands for bone craft in recent decades. Herein, we used Polyurethane (PU), a novel biocompatible and flexible polymer, and Hydroxyapatite (HA), the major component of human hard tissues matrix for developing new scaffolds and analyzing the in vitro osteogenic differentiation potential of human adipose‐derived mesenchymal stem cells (Ad‐MSCs) in basal and induction media. Gene expression analysis was performed to evaluate the expression level of four osteogenic differentiation genes. MTT assays were also done to assess the attachment and proliferation of the cells after 7 and 21 days of seeding to scaffolds. The expression level of RUNX2 was increased in seeded cells on PU/HA scaffolds compared with the PU. Cellular adhesion and proliferation of the Ad‐MSCs were higher in PU/HA than PU scaffolds according to the histology analysis. The PU and PU/HA scaffolds supported the attachment, proliferation, and differentiation of Ad‐MSCs, and they are suitable candidates for producing constructs in bone regeneration. However, further in‐vitro and in‐vivo studies on these scaffolds are needed to introduce an appropriate candidate for clinical bone regeneration.
A 2‐component Camassa‐Holm Equation, Euler‐Bernoulli Beam Problem, and Noncommutative Continued Fractions
Authors: Beals Richard , Szmigielski Jacek
Published: August 2022

A new approach to the Euler‐Bernoulli beam based on an inhomogeneous matrix string problem is presented. Three ramifications of the approach are developed:

motivated by an analogy with the Camassa‐Holm equation a class of isospectral deformations of the beam problem is formulated;

a reformulation of the matrix string problem in terms of a certain compact operator is used to obtain basic spectral properties of the inhomogeneous matrix string problem with Dirichlet boundary conditions;

the inverse problem is solved for the special case of a discrete Euler‐Bernoulli beam. The solution involves a noncommutative generalization of Stieltjes’ continued fractions, leading to the inverse formulas expressed in terms of ratios of Hankel‐like determinants.

© 2022 Courant Institute of Mathematics and Wiley Periodicals LLC.
Preclinical and Phase 1 Assessment of Antisense Oligonucleotide Bepirovirsen in Hepatitis B Virus–Transgenic Mice and Healthy Human Volunteers: Support for Clinical Dose Selection and Evaluation of Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses
Authors: Han Kelong , Theodore Dickens , McMullen Gina , Swayze Eric , McCaleb Michael , Billioud Gaetan , Wieland Stefan , Hood Steve , Paff Melanie , Bennett C. Frank , Kwoh T. Jesse
Published: August 2022

Dose‐dependent reductions in hepatitis B virus (HBV) RNA, DNA, and viral proteins following bepirovirsen administration were observed in HepG2.2.15 cells. In HBV‐transgenic mice treated at 50 mg/kg/wk, hepatic HBV RNA and DNA were reduced by 90% and 99%, respectively. Subsequently, a phase 1 first‐in‐human study assessed pharmacokinetics and tolerability of single (75–450 mg) and multiple (150–450 mg on days 1, 4, 8, 11, 15, and 22) subcutaneous bepirovirsen doses in 96 healthy volunteers. Bepirovirsen at all dose levels was rapidly absorbed (maximum plasma concentration 3–8 hours after dosing), rapidly distributed to peripheral tissues, and slowly eliminated (median plasma terminal half‐life: 22.5–24.6 days across cohorts). Plasma exposure (dose‐proportional at 150–450 mg) and concentration‐time profiles were similar following the first and sixth doses, suggesting little to no plasma accumulation (steady state achieved by day 22). Renal elimination of full‐length bepirovirsen accounted for <2% of the total dose. Across the single and multiple dose cohorts, 197 treatment‐emergent adverse events were reported, with 99% and 65% classified as mild in severity and local injection site reactions, respectively. In conclusion, bepirovirsen showed an acceptable safety profile in humans with observed pharmacokinetics consistent with the chemical class, warranting further evaluation of bepirovirsen in chronic HBV infection.