bluuebunny/crossref_metadata_2025 huggingface dataset:
Compromised Cytoarchitecture and Polarized Trafficking in Autosomal Dominant Polycystic Kidney Disease Cells
Authors: Charron Audra J. , Nakamura Sakie , Bacallao Robert , Wandinger-Ness Angela
Published: July 2002

Cystogenesis associated with autosomal dominant polycystic kidney disease (ADPKD) is characterized by perturbations in the polarized phenotype and function of cyst-lining epithelial cells. The polycystins, the protein products of the genes mutated in the majority of ADPKD cases, have been described recently, but the pathological mechanism by which causal mutations result in the mislocalization of cell membrane proteins has remained unclear. This report documents the dissociation from the ADPKD cell basolateral membrane of three molecules essential for spatial organization and exocytosis. The adherens junction protein E-cadherin, the subcellular disposition of which governs intercellular and intracellular architecture, was discovered sequestered in an internal ADPKD cell compartment. At the same time, sec6 and sec8, components of a complex critical for basolateral cargo delivery normally arrayed at the apico-lateral apex, were depleted from the ADPKD cell plasma membrane. An analysis of membrane transport revealed that basolateral trafficking of proteins and lipids was impaired as a result of delayed cargo exit from the ADPKD cell Golgi apparatus. Apical transport proceeded normally. Taken together with recent documentation of an association between polycystin-1 and E-cadherin (Huan and van Adelsberg 1999), the data suggest that causal mutations disrupt E-cadherin–dependent cytoarchitecture, adversely affecting protein assemblies crucial for basolateral trafficking.
A fluorescent resonant energy transfer–based biosensor reveals transient and regional myosin light chain kinase activation in lamella and cleavage furrows
Authors: Chew Teng-Leong , Wolf Wendy A. , Gallagher Patricia J. , Matsumura Fumio , Chisholm Rex L.
Published: July 2002

Approaches with high spatial and temporal resolution are required to understand the regulation of nonmuscle myosin II in vivo. Using fluorescence resonance energy transfer we have produced a novel biosensor allowing simultaneous determination of myosin light chain kinase (MLCK) localization and its [Ca2+]4/calmodulin-binding state in living cells. We observe transient recruitment of diffuse MLCK to stress fibers and its in situ activation before contraction. MLCK is highly active in the lamella of migrating cells, but not at the retracting tail. This unexpected result highlights a potential role for MLCK-mediated myosin contractility in the lamella as a driving force for migration. During cytokinesis, MLCK was enriched at the spindle equator during late metaphase, and was maximally activated just before cleavage furrow constriction. As furrow contraction was completed, active MLCK was redistributed to the poles of the daughter cells. These results show MLCK is a myosin regulator in the lamella and contractile ring, and pinpoints sites where myosin function may be mediated by other kinases.
Crucial Role of the Residue R280 at the F′–G′ Loop of the Human Granulocyte/Macrophage Colony-stimulating Factor Receptor α Chain for Ligand Recognition
Authors: Rajotte D. , Cadieux C. , Haman A. , Wilkes B.C. , Clark S.C. , Hercus T. , Woodcock J.A. , Lopez A. , Hoang T.
Published: July 2002

The receptor for granulocyte/macrophage colony-stimulating factor (GM-CSF) is composed of two chains, α and βc. Both chains belong to the superfamily of cytokine receptors characterized by a common structural feature, i.e., the presence of at least two fibronectin-like folds in the extracellular domain, which was first identified in the growth hormone receptor. The GM-CSF receptor (GMR)-α chain confers low affinity binding only (5–10 nM), whereas the other chain, βc, does not bind GM-CSF by itself but confers high affinity binding when associated with GMR-α (25–100 pM). The present study was designed to define the assembly of the GMR complex at the molecular level through site-directed mutagenesis guided by homology modeling with the growth hormone receptor complex. In our three-dimensional model, R280 of GMR-α, located in the F′–G′ loop and close to the WSSWS motif, is in the vicinity of the ligand Asp112, suggesting the possibility of electrostatic interaction between these two residues. Through site directed mutagenesis, we provide several lines of evidence indicating the importance of electrostatic interaction in ligand–receptor recognition. First, mutagenesis of GMR-αR280 strikingly ablated ligand binding in the absence of β common (βc); ligand binding was restored in the presence of βc with, nonetheless, a significant shift from high (26 pM) toward low affinity (from 2 to 13 nM). The rank order of the dissociation constant for the different GMR-αR280 mutations where Lys > Gln > Met > Asp, suggesting the importance of the charge at this position. Second, a mutant GM-CSF with charge reversal mutation at position Asp112 exhibited a 1,000-fold decrease in affinity in receptor binding, whereas charge ablation or conservative mutations were the least affected (10–20-fold). Third, removal of the charge at position R280 of GMR-α introduced a 10-fold decrease in the association rate constant and only a 2-fold change in the dissociation rate constant, suggesting that R280 is implicated in ligand recognition, possibly through interaction with Asp112 of GM-CSF. For all R280 mutants, the half-efficient concentrations of GM-CSF required for membrane (receptor binding) to nuclear events (c-fos promoter activation) and cell proliferation (thymidine incorporation) were in the same range, indicating that the threshold for biologic activity is governed mainly by the affinity of ligand–receptor interaction. Furthermore, mutation of other residues in the immediate vicinity of R280 was less drastic. Sequence alignment and modeling of interleukin (IL)-3R and IL-5R identified an arginine residue at the tip of a β turn in a highly divergent context at the F′–G′ loop, close to a conserved structural element, the WSXWS motif, suggesting the possibility of a ligand association mechanism similar to the one described herein for GMR.
Activation of CPP32-like Proteases Is Not Sufficient to Trigger Apoptosis: Inhibition of Apoptosis by Agents that Suppress Activation of AP24, but Not CPP32-like Activity
Authors: Wright Susan C. , Schellenberger Ute , Wang Hong , Kinder David H. , Talhouk Jamil W. , Larrick James W.
Published: July 2002

The 24-kD apoptotic protease (AP24) is a serine protease that is activated during apoptosis and has the capacity to activate internucleosomal DNA fragmentation in isolated nuclei. This study examined the following: (a) the functional relationship between AP24 and the CPP32-like proteases of the caspase family; and (b) whether activation of CPP32-like proteases is sufficient to commit irreversibly a cell to apoptotic death. In three different leukemia cell lines, we showed that agents that directly (carbobenzoxy-Ala-Ala-borophe (DK120) or indirectly inhibit activation of AP24 (protein kinase inhibitors, basic fibroblast growth factor, tosylphenylalaninechloromethylketone, and caspase inhibitors) protected cells from apoptosis induced by TNF or UV light. Only the caspase inhibitors, however, prevented activation of CPP32-like activity as revealed by cleavage of the synthetic substrate, DEVD-pNa, by cell cytosols, and also by in vivo cleavage of poly (ADP-ribosyl) polymerase, a known substrate of CPP32. Activation of DEVD-pNa cleaving activity without apoptosis was also demonstrated in two variants derived from the U937 monocytic leukemia in the absence of exogenous inhibitors. Cell-permeable peptide inhibitors selective for CPP32-like proteases suppressed AP24 activation and apoptotic death. These findings indicate that CPP32-like activity is one of several upstream signals required for AP24 activation. Furthermore, activation of CPP32-like proteases alone is not sufficient to commit irreversibly a cell to apoptotic death under conditions where activation of AP24 is inhibited.
P-loop Flexibility in Na+ Channel Pores Revealed by Single- and Double-cysteine Replacements
Authors: Tsushima Robert G. , Li Ronald A. , Backx Peter H.
Published: July 2002

Replacement of individual P-loop residues with cysteines in rat skeletal muscle Na+ channels (SkM1) caused an increased sensitivity to current blockade by Cd2+ thus allowing detection of residues lining the pore. Simultaneous replacement of two residues in distinct P-loops created channels with enhanced and reduced sensitivity to Cd2+ block relative to the individual single mutants, suggesting coordinated Cd2+ binding and cross-linking by the inserted sulfhydryl pairs. Double-mutant channels with reduced sensitivity to Cd2+ block showed enhanced sensitivity after the application of sulfhydryl reducing agents. These results allow identification of residue pairs capable of approaching one another to within less than 3.5 Å. We often observed that multiple consecutive adjacent residues in one P-loop could coordinately bind Cd2+ with a single residue in another P-loop. These results suggest that, on the time-scale of Cd2+ binding to mutant Na+ channels, P-loops show a high degree of flexibility.
A fast algorithm for Gaussian type quadrature formulae with mixed boundary conditions and some lumped mass spectral approximations
Authors: Ezzirani Abdelkrim , Guessab Allal
Published: July 2002

After studying Gaussian type quadrature formulae with mixed boundary conditions, we suggest a fast algorithm for computing their nodes and weights. It is shown that the latter are computed in the same manner as in the theory of the classical Gauss quadrature formulae. In fact, all nodes and weights are again computed as eigenvalues and eigenvectors of a real symmetric tridiagonal matrix. Hence, we can adapt existing procedures for generating such quadrature formulae. Comparative results with various methods now in use are given. In the second part of this paper, new algorithms for spectral approximations for second-order elliptic problems are derived. The key to the efficiency of our algorithms is to find an appropriate spectral approximation by using the most accurate quadrature formula, which takes the boundary conditions into account in such a way that the resulting discrete system has a diagonal mass matrix. Hence, our algorithms can be used to introduce explicit resolutions for the time-dependent problems. This is the so-called lumped mass method. The performance of the approach is illustrated with several numerical examples in one and two space dimensions.
SSMAL: similarity searching with alignment graphs.
Authors: Nicod√®me P
Published: July 2002

MOTIVATION: We want to provide biologists with a fast and sensitive scanning tool for searching local alignments of a protein query sequence against databases of protein multiple alignments, such as ProDom. Conversely, we want to provide a tool for locally aligning a protein multiple alignment query against a protein database such as SWISSPROT. RESULTS: We developed the program SSMAL (Shuffling Similarities with Multiple Alignments) which utilizes features of the Blast (Altschul et al., J. Mol. Biol., 215, 403-410, 1990) algorithm and part of the Blast code. Our software allows both scanning of multiple alignments and searching with a multiple alignment. Deletions in the multiple alignment only are handled and a SSMAL search may miss some similarities found by a profile search. However, an SSMAL scan of a database such as ProDom would be 20-30 times faster that a profile scan. In the worst case, a SSMAL search is approximately 9 times faster than a profile search. AVAILABILITY: http://www.dkfz-heidelberg.de/tbi/ people/nicodeme and follow the hyperlink SSMAL. CONTACT: p.nicodeme@DKFZ-Heidelberg.de
A model system for studying the integration of molecular biology databases.
Authors: Macauley J , Wang H , Goodman N
Published: July 2002

MOTIVATION: Integration of molecular biology databases remains limited in practice despite its practical importance and considerable research effort. The complexity of the problem is such that an experimental approach is mandatory, yet this very complexity makes it hard to design definitive experiments. This dilemma is common in science, and one tried-and-true strategy is to work with model systems. We propose a model system for this problem, namely a database of genes integrating diverse data across organisms, and describe an experiment using this model. RESULTS: We attempted to construct a database of human and mouse genes integrating data from GenBank and the human and mouse genome-databases. We discovered numerous errors in these well-respected databases: approximately 15% of genes are apparently missing from the genome-databases; links between the sequence and genome-databases are missing for another 5-10% of the cases; about a third of likely homology links are missing between the genome-databases; 10-20% of entries classified as 'genes' are apparently misclassified. By using a model system, we were able to study the problems caused by anomalous data without having to face all the hard problems of database integration. CONTACT: nat@jax.org
A new method to predict the consensus secondary structure of a set of unaligned RNA sequences.
Authors: Bouthinon D , Soldano H
Published: July 2002

MOTIVATION: To predict the consensus secondary structure, possibly including pseudoknots, of a set of RNA unaligned sequences. RESULTS: We have designed a method based on a new representation of any RNA secondary structure as a set of structural relationships between the helices of the structure. We refer to this representation as a structural pattern. In a first step, we use thermodynamic parameters to select, for each sequence, the best secondary structures according to energy minimization and we represent each of them using its corresponding structural pattern. In a second step, we search for the repeated structural patterns, i.e. the largest structural patterns that occur in at least one sequence, i.e. included in at least one of the structural patterns associated to each sequence. Thanks to an efficient encoding of structural patterns, this search comes down to identifying the largest repeated word suffixes in a dictionary. In a third step, we compute the plausibility of each repeated structural pattern by checking if it occurs more frequently in the studied sequences than in random RNA sequences. We then suppose that the consensus secondary structure corresponds to the repeated structural pattern that displays the highest plausibility. We present several experiments concerning tRNA, fragments of 16S rRNA and 10Sa RNA (including pseudoknots); in each of them, we found the putative consensus secondary structure.
Sequence-structure specificity of a knowledge based energy
function at the secondary structure level
Authors: Xu Dong , Unseren Michael A. , Xu Ying , Uberbacher Edward C.
Published: July 2002

*To whom correspondence should be addressed.

Motivation: This paper investigates the sequence-structure specificity of a representative knowledge based energy function by applying it to threading at the level of secondary structures of proteins. Assessing the strengths and weaknesses of an energy function at this fundamental level provides more detailed and insightful information than at the tertiary structure level and the results obtained can be useful in tertiary level threading.

Results: We threaded each of the 293 non-redundant proteins onto the secondary structures contained in its respective native protein (host template). We also used 68 pairs of proteins with similar folds and low sequence identity. For each pair, we threaded the sequence of one protein onto the secondary structures of the other protein. The discerning power of the total energy function and its one-body, pairwise, and mutation components is studied. We then applied our energy function to a recent study which demonstrated how a designed 11-amino acid sequence can replace distinct segments (one segment is an α-helix, the other is a β-sheet) of a protein without changing its fold. We conducted random mutations of the designed sequence to determine the patterns for favorable mutations. We also studied the sequence-structure specificity at the boundaries of a secondary structure. Finally, we demonstrated how to speed up tertiary level threading by filtering out alignments found to be energetically unfavorable during the secondary structure threading.

Availability: The program is available on request from the authors.

Contact: xud@ornl.gov
Bioinformatics and the theoretical foundations of molecular
biology
Authors: Ouzounis Christos
Published: July 2002

1 Email: ouzounis@ebi.ac.uk; URL: http://www.genomes.org
An oscillatory route to extinction for solid fuel combustion waves due to heat losses
Authors: Mercer G. N. , Weber R. O. , Sidhu H. S.
Published: July 2002

A numerical method is used to show that heat loss increases can lead to a period–doubling route to the cessation of propagation of solid fuel combustion. Oscillatory combustion waves are found in certain regions of the parameter space. The behaviour of these oscillatory waves becomes more complex as the heat loss is increased until extinction of the combustion reaction occurs. Large excursions in temperature, above the adiabatic temperature, are possible in the non–adiabatic case close to this extinction point.
Epithelial carcinogenesis in the mouse: correlating the genetics and the biology
Authors: Frame Sheelagh , Crombie Robbie , Liddell Jennie , Stuart Debbie , Linardopoulos Spiros , Nagase Hiroki , Portella Giuseppe , Brown Ken , Street Alasdair , Akhurst Rosemary , Balmain Allan
Published: July 2002

Tumour formation relies on a complex combination of genetic and environmental factors. In particular, the contributions from inherited predisposition genes as well as carcinogens, for example from cigarettes or in the diet, are amongst the major contributors to tumorigenesis. Since the study of such processes is particularly difficult in human cancers, the availability of a well–defined model system is of obvious benefit. The mouse skin model of multistage carcinogenesis offers an excellent tool for the study of the target cells, the target genes and the biological events associated with neoplasia. In this system, tumorigenesis occurs in a series of defined stages, each of which is characterized by specific and reproducible alterations in genes such as H–ras, cyclin D1,p53andp16INK4A. Additional changes occur in the production of, or response to, factors such as transforming growth factorβ (TGFβ). These genetic and biological alterations are mirrored in human tumours of epithelial origin. Hence, research into the general principles of tumour initiation, promotion and progression in the context of the mouse skin model is likely to prove valuable in the continual search for new methods for the diagnosis, prevention, and therapeutic treatment of human cancers.
Genetic analysis of phenotype in
Trypanosoma brucei
: a classical approach to potentially complex traits
Authors: Tait Andy , Masiga Dan , Ouma Johnstone , MacLeod Annette , Sasse Juergen , Melville Sara , Lindegard Gabbi , McIntosh Anne , Turner Mike
Published: July 2002

The genome of the African trypanosome,
Trypanosoma brucei
, is currently being sequenced, raising the question of how the data generated can be used to determine the function of the large number of genes that will be identified. There is a range of possible approaches, and in this paper we discuss the use of a classical genetic approach coupled with positional cloning based on the ability of trypanosomes to undergo genetic exchange. The genetics of these parasites is essentially similar to a conventional diploid Mendelian system with allelic segregation and an independent assortment of markers on different chromosomes. Data are presented showing that recombination occurs between markers on the same chromosome allowing the physical size of the unit of recombination to be determined. Analysis of the available progeny clones from a series of crosses shows that, in principal, large numbers of progeny can readily be isolated from existing cryopreserved products of mating and, taking these findings together, it is clear that genetic mapping of variable phenotypes is feasible. The available phenotypes for analysis are outlined and most are relevant to the transmission and pathogenesis of the parasite. Genetic maps from two crosses are presented based on the use of the technique of AFLP; these maps comprise 146 and 139 markers in 30 and 21 linkage groups respectively. Segregation distortion is exhibited by some of the linkage groups and the possible reasons for this are discussed. The general conclusion, from the results presented, is that a genetic-mapping approach is feasible and will, in the future, allow the genes determining a number of important traits to be identified.
Experimental study of geo-acoustic inversion uncertainty due to ocean sound-speed fluctuations
Authors: Siderius Martin , Nielsen Peter L. , Sellschopp Jürgen , Snellen Mirjam , Simons Dick
Published: July 2002

Acoustic data measured in the ocean fluctuate due to the complex time-varying properties of the channel. When measured data are used for model-based, geo-acoustic inversion, how do acoustic fluctuations impact estimates for the seabed properties? In May 1999 SACLANT Undersea Research Center and TNO-Physics and Electronics Laboratory (FEL), conducted a shallow-water experiment on the Adventure Bank off the southwest coast of Sicily, Italy to assess the effects of a time-varying ocean on acoustic propagation and geo-acoustic inversion. A favorable area for acoustic propagation was identified which had slight internal wave activity and a weakly range-dependent bathymetry with sand-like bottom properties. Oceanographic and acoustic measurements were performed continuously over a 3-day period. Broadband (0.2–3.8 kHz) acoustic signals from a bottom-moored source were transmitted over fixed paths and received on a moored vertical hydrophone array. During the transmissions extensive environmental measurements (e.g., sound speed, current, sea-surface waveheight, etc.) were made to correlate the time-varying environmental and acoustic data. Modeled acoustic data show time variability which agrees with the measurements. Results illustrate severe problems when modeling shallow-water acoustic propagation at ranges beyond a few kilometers in the frequency band considered. Further, the acoustic fluctuations in time caused erroneous time variability in inverted seabed properties.
Asymmetry of masking revisited: Generalization of masker and probe bandwidth
Authors: Hall Joseph L.
Published: July 2002

A band of noise masked by a tone is audible at a much lower intensity increment between masker alone and masker plus just-detectable probe than is a tone masked by a band of noise. To better understand the mechanisms responsible for this asymmetry of masking, we measured thresholds of probe signals ranging in bandwidth from 0 to 256 Hz in the presence of masking signals also ranging in bandwidth from 0 to 256 Hz. Masker and probe center frequencies were 1 kHz in all cases. Two versions of the experiment are reported: (1) masker intensity constant at 70 dB SPL and (2) masker intensity roved over the range 65–75 dB SPL. The results confirm and extend previous results. For a fixed masker bandwidth, threshold intensity increments are essentially constant, and accounted for by a model based on long-term average energy, so long as probe bandwidth does not exceed masker bandwidth. If probe bandwidth exceeds masker bandwidth, threshold intensity increments decrease sharply for all masker bandwidths tested. Roved-intensity results are consistent with the hypothesis that detection is based on long-term average energy for probe bandwidth equal to or less than masker bandwidth, but that for probe bandwidth greater than masker bandwidth other cues are utilized. In addition, we investigated the possible contribution of off-frequency listening by developing and presenting results from a frequency-selective model of peripheral masking. Model results argue against detection based on spectral cues associated with off-frequency listening for signal bandwidths less than a critical band. The conclusion is that detection must utilize the temporal structure of the signal for probe bandwidth greater than masker bandwidth.
A generalized internal source density method for the forward and backward projection of harmonic pressure fields from complex bodies
Authors: Stepanishen Peter R.
Published: July 2002

A generalized internal source density (GISD) method is presented to address the forward and backward projection of harmonic pressure fields from complex three-dimensional bodies. The GISD approach is based on decomposing the field on a closed surface of revolution in the fluid into a summation of circumferential orders where the pressure field for each order is associated with an internal linear distribution of ring sources on the axis of revolution of the surface. Both Dirichlet and Neumann boundary value problems may be addressed using the approach in which the axial variation of each ring source distribution is formulated as the solution of a minimum mean square error problem which is subsequently solved using SVD methods. The resulting linear distributions of ring sources can be simply used to determine the entire pressure and velocity fields of a complex harmonically vibrating body. In particular, the pressure and/or normal velocity on a vibrating body can be readily obtained from the pressure field over a closed surface. Local intensity and radiated power can thus be simply obtained. Far field pressures are simply obtained from the axial Fourier transforms of the ring source distributions. Several examples are presented to illustrate the behaviour of the source distributions for spherical geometries. The analytical results obtained via the GISD method agree with those obtained via classical methods.
Signal processing of the echo signatures returned by submerged shells insonified by dolphin “clicks:” Active classification
Authors: Gaunaurd Guillermo C. , Brill Donald , Huang Hanson , Moore Patrick W. B. , Strifors Hans C.
Published: July 2002

A large set of dolphin-emitted acoustic pulses (“echolocation clicks”) have been examined, which were reflected from various elastic shells that were suspended, underwater, 4.5 m in front of the animal in a large test site in Kaneohe Bay, Hawaii. A carefully instrumented analog-to-digital system continuously captured the emitted clicks and also the returned, backscattered echoes (A/D conversion at 500 kHz). Using standard conditioning techniques and food reinforces, the dolphin is taught to push an underwater paddle when the “correct” target—the one he has been trained to identify—is presented to him. He communicates his consistently correct identifying choices in this manner. Many echoes returned by three types of cylindrical shells in both the time and frequency domains as well as in the joint time-frequency (t-f) domain, by means of Wigner-type distributions have been examined. It will be shown exactly how specific features observable in these displays are directly related to the physical characteristics of the shells. This processing takes advantage of certain fundamental resonance principles to show which echo features contain information about the size, shape, wall thickness, and material composition of both the shell and its filler substance. In the same fashion that these resonance features give the identifying characteristics of each shell, it is believed they may also give them to the dolphin. These echo features may allow him to extract the target properties by inspection without any need for computations. It is claimed that this may be the fundamental physical explanation of the dolphin’s amazing target ID feats, upon which they base their recognition choices. This claim may be substantiated by the detailed analysis of many typical echoes returned by various shells, when they are interrogated by several dolphins. Thus far, this analysis of many echoes from many shells has only been carried out for a single dolphin.
Bilingual exposure and some consequences on native-language recognition processes at four months
Authors: Bosch Laura
Published: July 2002

Evidence of language-specific influences on infants’ speech perception presupposes the existence of a basic level of native-language representation. Findings from a language discrimination task, indicating that two-month-old infants perform successfully only when one of the two languages is the native one, but not when both are unfamiliar languages, have been interpreted as evidence that a primary representation of the structure of the native language has been reached, and is probably based on the prosodic/rhythmic properties of the input language (Mehler et al., 1996). The capacity to discriminate languages seems also to be dependent on their prosodic distance. Recent research in this laboratory has addressed the issue of language discrimination for a prosodically close pair of Romance languages, i.e., Spanish and Catalan. While four-month-old infants from monolingual environments seem able to recognize their native language, either Spanish or Catalan, infants from bilingual families did not show a preference for either language. In a second series of experiments, infants from bilingual environments were tested with the same procedure, this time selecting one of their familiar languages to be contrasted with a completely unfamiliar one (English and also Italian). When compared to infants from monolingual families, they showed slower orientation latencies toward the familiar language.
Broadband model-based processing for shallow ocean environments
Authors: Candy J. V. , Sullivan E. J.
Published: July 2002

Most acoustic sources found in the ocean environment are spatially complex and broadband. In the case of shallow water propagation, these source characteristics complicate the analysis of received acoustic data considerably. A common approach to the broadband problem is to decompose the received signal into a set of narrow-band lines. This then allows the problem to be treated as a multiplicity of narrow-band problems. Here a model-based approach is developed for the processing of data received on a vertical array from a broadband source where it is assumed that the propagation is governed by the normal-mode model. The goal of the processor is to provide an enhanced (filtered) version of the pressure at the array and the modal functions. Thus a pre-processor is actually developed, since one could think of several applications for these enhanced quantities such as localization, modal estimation, etc. It is well-known that in normal-mode theory a different modal structure evolves for each temporal frequency; thus it is not surprising that the model-based solution to this problem results in a scheme that requires a “bank” of narrow-band model-based processors—each with its own underlying modal structure for the narrow frequency band it operates over. The “optimal” Bayesian solution to the broadband pressure field enhancement and modal function extraction problem is developed. It is shown how this broadband processor can be implemented (using a suboptimal scheme) in pseudo real time due to its inherent parallel structure. A set of noisy broadband data is synthesized to demonstrate how to construct the processor and achieve a minimum variance (optimal Bayesian) design. It is shown that both broadband pressure-field and modal function estimates can be extracted illustrating the feasibility of this approach.
Overview of the infrasound monitoring system for the Comprehensive Nuclear-Test-Ban Treaty
Authors: Christie Douglas R.
Published: July 2002

A global network of 60 infrasonic array stations is being established as part of a global monitoring system for verification of the Comprehensive Nuclear-Test-Ban Treaty. These ultrasensitive stations, which are distributed as uniformly as possible over the surface of the globe, will be capable of detecting and locating any nuclear explosion in the atmosphere with yields of 1 Kt or more. In addition to nuclear explosions, this network will detect infrasound from a wide range of man-made and naturally occurring sources, including large chemical explosions, meteors, volcanic explosions, aerodynamic infrasound associated with orographic features, and auroral-generated infrasound. The propagation of infrasound in the atmosphere is not, as yet, fully understood. The analysis of data from this network should provide considerable insight into the detailed long-range propagation properties of low-frequency sound in a temporally and spatially inhomogeneous medium.
Neural responses to the onset of voicing are unrelated to other measures of temporal resolution
Authors: Sinex Donal G. , Chen Guang-Di
Published: July 2002

Voice onset time (VOT) is a temporal cue that can distinguish consonants such as /d/ from /t/. It has previously been shown that neurons’ responses to the onset of voicing are strongly dependent on their static spectral sensitivity. This study examined the relation between temporal resolution, determined from responses to sinusoidally amplitude-modulated (SAM) tones, and responses to syllables with different VOTs. Responses to syllables and SAM tones were obtained from low-frequency neurons in the inferior colliculus (IC) of the chinchilla. VOT and modulation period varied from 10 to 70 ms in 10-ms steps, and discharge rates elicited by stimuli whose amplitude envelopes were modulated over the same temporal interval were compared. Neurons that respond preferentially to syllables with particular VOTs might be expected to respond best to the SAM tones with comparable modulation periods. However, no consistent agreement between responses to VOT syllables and to SAM tones was obtained. These results confirm the previous suggestion that IC neurons’ selectivity for VOT is determined by spectral rather than temporal sensitivity.
Sound cancellation by the use of secondary multipoles: Experiments
Authors: Beauvilain Thierry A. , Bolton J. Stuart , Gardner Bryce K.
Published: July 2002

Theory related to global, free-field cancellation of a primary monopole field by the use of a displaced, secondary multipole was presented previously: a corresponding experimental investigation is presented here. The construction of multipole source components to octopole order is described, as are procedures for determining their source strengths. Dipoles, longitudinal quadrupoles, and longitudinal octopoles that conformed closely to their theoretical models were constructed using arrays of unbaffled loudspeakers. Two methods of calculating the multipole strengths required to cancel a primary monopole field were implemented in an open-loop manner: a “direct” approach based on a multipole expansion of the primary field, and a least-squares procedure based on fitting the secondary field to the primary field either along a circle enclosing a secondary source, or along a segment of that circle. Cancellation measurements were made on a 1-m-radius circle centered on the secondary source: the primary-to-secondary source separation was approximately 0.2 wavelengths. It was found both that a secondary multipole could provide far greater cancellation than a monopole placed at the same distance from the primary source and that the least-squares approach resulted in greater far-field cancellation than did the direct approach.
Imaging a moving target using forward-look synthetic aperture sonar
Authors: Edelson Geoffrey S. , Gedney Charles J. , Abbot Philip A. , Dyer Ira , Rolt Kenneth D.
Published: July 2002

Mid-frequency active, surface ship sonar data from a recent shallow-water sea trial have been processed using synthetic aperture sonar (SAS) algorithms. The target of opportunity closed head-on directly toward the surface ship at a relative speed of 13 knots through an acoustic environment that was characterized by a downward refracting sound speed profile in 100-m-depth water over a sand/mud bottom during calm seas. This situation represents an endfire (90-degree squint angle) scenario for which the resolution of any line array (synthetic or real) is considerably degraded relative to the broadside case. The test was not designed for SAS application so the aperture is significantly undersampled. The processing approach utilizes signal adaptive, ping-to-ping correlation autofocusing to correct for the effects of platform and target motion, and for ocean instabilities. The processing is tuned to the specific environment by setting the cross-correlation window size based on the two-way group arrival structure of the channel. The aliasing that results from the undersampled aperture is reduced to acceptable levels through the appropriate use of cross-range matched field processing. Images formed by processing the data from a forward-look synthetic aperture measuring 2200 wavelengths with a mean target distance of 9.5 km are presented.
Refined multiload method for measuring acoustical source characteristics of an intake or exhaust system
Authors: Jang Seung-Ho , Ih Jeong-Guon
Published: July 2002

The one-port source characteristics in a duct system, viz., source impedance and strength, can be determined by using the four-load method. In this paper, to avoid the instability problem of the conventional four-load method, a new formulation for the multiload method has been proposed, which employs an error function based on the linear, time-invariant source model. It is shown that the method is less sensitive to input errors compared to the previous methods. For a 10% input error, the proposed method yields a relative error in the source resistance that is about 1/100 times smaller than for the conventional method. The effectiveness of the present method is demonstrated by two test examples, a loudspeaker and a blower, each operating in a duct. It is observed that the conventional and least-squares methods result in large errors, whereas the present method yields far better agreement with the actual source parameters, as measured by the direct method. The present method is then used to obtain the source parameters on the exhaust side of an operating internal combustion engine. The radiated sound spectrum from the exhaust opening is predicted by using the measured source parameters and the calculated result agrees very well with the measured one.
Transient response of concentrated suspensions after shear reversal
Authors: Narumi Takatsune , See Howard , Honma Yuichi , Hasegawa Tomiichi , Takahashi Tsutomu , Phan-Thien Nhan
Published: July 2002

We have examined the transient stress response under shear flow of concentrated suspensions of non-Brownian spheres. We focused on the experiment where the shearing is momentarily stopped and restarted in the opposite direction. We found that the normalized stress recovery curves for different values of the initial and subsequent shear rates could be collapsed quite well if plotted against the strain. This behavior agrees with the basic concept that the transient stress behavior is a function only of the imposed strain, as predicted by some recent constitutive models of concentrated suspensions. We also found that the transient behavior of the normal stress difference showed similar data collapse. Further, there appeared to be little qualitative difference in the behavior of particulate systems with a high degree of size monodispersity and those more polydisperse.
The Design and Calibration of a Stress Relaxation Ball Indentation Penetrometer
Authors: Chapoy L. Lawrence , Aklonis John J.
Published: July 2002

A stress relaxation ball indentation penetrometer was designed and constructed with the intent of measuring the time-dependent stress relaxation modulus of materials incapable of supporting their own weight. An equation is derived to relate the modulus to the geometry of a deformation by a sphere into a plane. The relevance of this equation to creep experiments is discussed.
Shear-Induced Thinning and Thickening of Raw Cement Slurries: Effect of Simple Ions and Polyelectrolytes
Authors: Yaron I. , Ishshalom M.
Published: July 2002

Additions of some polyelectrolytes intended to induce thinning of slurries sometimes cause the opposite effect. At a given level of ion concentration in the slurry water, increasing the amount of polyelectrolyte (sodium tripolyphosphate or sodium humate) additions caused inversion from shear-induced thinning to shear-induced thickening. The concentration of polyelectrolytes at inversion shifted towards lower values with reduced concentration of ions in the slurry water. A qualitative interpretation of the mechanism of the phenomenon is proposed, based on the effects of the structure of montmorillonite clays. These involve facilitating shear-induced flow orientation (thinning) by polyanionic adsorption at the edges and chemically promoted shear-induced breakdown of tactoids leading to thickening.
Powder diffraction of the cubic perovskite La0.2Sr0.8Fe0.8Co0.1Cr0.1O3−δ
Authors: Koster Herman , McCool Ben A.
Published: July 2002

The powder diffraction pattern of the new cubic perovskite material La0.2Sr0.8Fe0.8Co0.1Cr0.1O3−δ is described. The compound has a unit cell parameter of a=3.875 27(1) Å with Z=1 and Dx=5.75 g/cm3.
The antiviral drug telaprevir induces cell death by reducing FOXA1 expression in estrogen receptor α (ERα)‐positive breast cancer cells
Authors: Bartoloni Stefania , Leone Stefano , Pescatori Sara , Cipolletti Manuela , Acconcia Filippo
Published: August 2022

Previously, we found that telaprevir (Tel), the inhibitor of hepatitis C virus NS3/4A serine protease, reduces estrogen receptor α (ERα) content at the transcriptional level without binding to the receptor, prevents ERα transcriptional activity, and inhibits basal and 17β‐estradiol (E2)‐dependent cell proliferation in different breast cancer (BC) cell lines. Here, we further characterize the Tel action mechanisms on ERα levels and function, identify a possible molecular target of Tel in BC cells, and evaluate Tel as an antiproliferative agent for BC treatment. Tel‐dependent reduction in ERα levels and function depends on a Tel‐dependent decrease in FOXA1 levels and activity. The effect of Tel is transduced by the IGF1‐R/AKT/FOXA1 pathway, with the antiviral compound interacting with IGF1‐R. Tel prevents the proliferation of several BC cell lines, while it does not affect the proliferation of normal nontransformed cell lines, and its antiproliferative effect is correlated with the ratio of FOXA1/IGF1‐R expression. In conclusion, Tel interferes with the IGF1‐R/AKT/FOXA1 pathway and induces cell death in ERα‐expressing BC cells. Thus, we propose that this antiviral could be repurposed for the treatment of ERα‐expressing BC.
Reducing Optical Reflection Loss for Perovskite Solar Cells Via Printable Mesoporous SiO2 Antireflection Coatings
Authors: Wang Xiadong , Wang Wei , Liu Jiale , Qi Jianhang , He Yue , Wang Yifan , Hu Wenjing , Cheng Yanjie , Chen Kai , Hu Yue , Mei Anyi , Han Hongwei
Published: August 2022

The power conversion efficiency (PCE) of single‐junction perovskite solar cells (PSCs) is being rapidly promoted towards their theoretical limit, with a certified value of 25.7%. Reducing optical loss will further contribute to PCE improvement. Here, the optical loss including reflection loss, absorption loss, and transmission loss in printable mesoscopic perovskite solar cells (p‐MPSCs) is analyzed. A printable mesoporous SiO2 antireflection coating for improving the transmittance of the fluorine‐doped tin oxide (FTO) glass substrate by reducing optical reflection at the air/glass interface is reported. With modulated porosity and thickness, the mesoporous SiO2 film constructs a graded refractive index interface and increases the transmittance of FTO glass by ≈2%–4% in the spectral range of 350–800 nm at normal incident angle with the highest transmittance improved from 85% to 89%. The SiO2 coating also exhibits wide‐angle and broadband antireflection properties. The coatings successfully help p‐MPSCs obtain about an average 3% enhancement in the short‐circuit current density (JSC) and PCE. This study demonstrates the necessity of optical management for efficient solar cells and provides a cost‐effective and scalable antireflection coating for the future realistic application of PSCs.
Hollow Cu2O@CoMn2O4 Nanoreactors for Electrochemical NO Reduction to NH3: Elucidating the Void‐Confinement Effects on Intermediates
Authors: Bai Chunpeng , Fan Shiying , Li Xinyong , Niu Zhaodong , Wang Jing , Liu Zhiyuan , Zhang Dongke
Published: August 2022

Hollow nanoreactors show great potential in catalysis due to the void‐confinement effect. Yet few studies have investigated the void‐confinement effect of hollow nanoreactors on intermediates. Herein, electrochemical NO reduction to NH3 (ENOR) is used as a probe reaction to study the void‐confinement effect of hollow Cu2O@CoMn2O4 nanoreactors on intermediates. Combined with the results of catalytic activity, H2‐treated in situ diffusion Fourier transform infrared spectroscopy and the finite‐element method simulation confirm that the void‐confinement effect on the intermediate is the main reason for enhanced ENOR efficiency. Additionally, theoretical calculations also show that the Cu sites of Cu2O@CoMn2O4 nanoreactors are favorable for the formation of *NOH intermediates. This work not only gives an insight into void‐confinement effect of hollow nanoreactors on intermediates but also provides a valuable strategy for improving ENOR.
Interstitial Photothermal Therapy Generates Durable Treatment Responses in Neuroblastoma
Authors: Ledezma Debbie K. , Balakrishnan Preethi B. , Shukla Anshi , Medina Jacob A. , Chen Jie , Oakley Emily , Bollard Catherine M. , Shafirstein Gal , Miscuglio Mario , Fernandes Rohan
Published: August 2022

Photothermal therapy (PTT) represents a promising modality for tumor control typically using infrared light‐responsive nanoparticles illuminated by a wavelength‐matched external laser. However, due to the constraints of light penetration, PTT is generally restricted to superficially accessible tumors. With the goal of extending the benefits of PTT to all tumor settings, interstitial PTT (I‐PTT) is evaluated by the photothermal activation of intratumorally administered Prussian blue nanoparticles with a laser fiber positioned interstitially within the tumor. This interstitial fiber, which is fitted with a terminal diffuser, distributes light within the tumor microenvironment from the “inside‐out” as compared to from the “outside‐in” traditionally observed during superficially administered PTT (S‐PTT). I‐PTT improves the heating efficiency and heat distribution within a target treatment area compared to S‐PTT. Additionally, I‐PTT generates increased cytotoxicity and thermal damage at equivalent thermal doses, and elicits immunogenic cell death at lower thermal doses in targeted neuroblastoma tumor cells compared to S‐PTT. In vivo, I‐PTT induces significantly higher long‐term tumor regression, lower rates of tumor recurrence, and improved long‐term survival in multiple syngeneic murine models of neuroblastoma. This study highlights the significantly enhanced therapeutic benefit of I‐PTT compared to traditional S‐PTT as a promising treatment modality for solid tumors.