bluuebunny/crossref_metadata_2025 huggingface dataset:
Histidine-tagged wild-type yeast actin: Its properties and use in an approach for obtaining yeast actin mutants
Authors: Buzan Jenny , Du Jinyan , Karpova Tatiana , Frieden Carl
Published: July 2002

Wild-type and an N-terminal 6-histidine-tagged actin have each been expressed by using a yeast strain that contains the actin gene on a plasmid and not on the chromosome. Yeast strains have also been constructed that use two plasmids, one expressing the wild-type protein and the other the 6-histidine-tagged protein. Yeast cells can be grown with either plasmid alone or with both plasmids together and appear to be normal in that the growth rates of all the yeast strains are quite similar, as is the morphology of the yeast cells. The polymerization properties of the 6-histidine-tagged actin appear almost identical to wild-type actin expressed from the chromosome. When the wild-type and 6-histidine-tagged actin are coexpressed, they can be purified by standard techniques and then separated using nickel-nitrilotriacetate chromatography. The method can be used to prepare actin mutants including those that are nonfunctional or might not support yeast growth for other reasons.
Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site
Authors: Shriver Zachary , Raman Rahul , Venkataraman Ganesh , Drummond Katherine , Turnbull Jeremy , Toida Toshihiko , Linhardt Robert , Biemann Klaus , Sasisekharan Ram
Published: July 2002

Heparin- and heparan sulfate-like glycosaminoglycans (HLGAGs) represent an important class of molecules that interact with and modulate the activity of growth factors, enzymes, and morphogens. Of the many biological functions for this class of molecules, one of its most important functions is its interaction with antithrombin III (AT-III). AT-III binding to a specific heparin pentasaccharide sequence, containing an unusual 3-O sulfate on a N-sulfated, 6-O sulfated glucosamine, increases 1,000-fold AT-III's ability to inhibit specific proteases in the coagulation cascade. In this manner, HLGAGs play an important biological and pharmacological role in the modulation of blood clotting. Recently, a sequencing methodology was developed to further structure-function relationships of this important class of molecules. This methodology combines a property-encoded nomenclature scheme to handle the large information content (properties) of HLGAGs, with matrix-assisted laser desorption ionization MS and enzymatic and chemical degradation as experimental constraints to rapidly sequence picomole quantities of HLGAG oligosaccharides. Using the above property-encoded nomenclature-matrix-assisted laser desorption ionization approach, we found that the sequence of the decasaccharide used in this study is ΔU
2S
H
NS,6S
I
2S
H
NS,6S
I
2S
H
NS,6S
IH
NAc,6S
GH
NS,3S,6S
(±DDD4–7). We confirmed our results by using integral glycan sequencing and one-dimensional proton NMR. Furthermore, we show that this approach is flexible and is able to derive sequence information on an oligosaccharide mixture. Thus, this methodology will make possible both the analysis of other unusual sequences in HLGAGs with important biological activity as well as provide the basis for the structural analysis of these pharamacologically important group of heparin/heparan sulfates.
Colonizing nature: scientific knowledge, colonial power and the incorporation of India into the modern world‐system
Authors: Baber Zaheer
Published: July 2002

In this paper, the role of scientific knowledge, institutions and colonialism in mutually co‐producing each other is analysed. Under the overarching rubric of colonial structures and imperatives, amateur scientists sought to deploy scientific expertise to expand the empire while at the same time seeking to take advantage of the opportunities to develop their careers as ‘scientists’. The role of a complex interplay of structure and agency in the development of modern science, not just in India but in Britain too is analysed. The role of science and technology in the incorporation of South Asian into the modern world system, as well as the consequences of the emergent structures in understanding the trajectory of modern science in post‐colonial India is examined. Overall, colonial rule did not simply diffuse modern science from the core to the periphery. Rather the colonial encounter led to the development of new forms of scientific knowledge and institutions both in the periphery and the core.
The Tercentenary of Henry Martyn'sConsiderations upon the East-India Trade
Authors: Maneschi Andrea
Published: July 2002

Henry Martyn'sConsiderations Upon the East-India Trade, published anonymously in 1701, stands out as a major contribution to the field of political economy that took root in Britain in the eighteenth century, and to the demonstration of the gains from free trade (Martyn 1701). Martyn provided one of the earliest formulations (and by far the clearest) of what Jacob Viner termed the “eighteenth-century rule” for the gains from trade, that “it pays to import commodities from abroad whenever they can be obtained in exchange for exports at a smaller real cost than their production at home would entail” (Viner 1937, p. 440). The numerical examples that Martyn used to illustrate it went even beyond the case for free trade advanced seventy-five years later by Adam Smith inThe Wealth of Nations. Martyn's tract contains other remarkable insights that became important features of classical political economy, such as the nature and advantages of the division of labor, the dependence of the latter on the extent of the market, the workings of a market economy, the role of money, and the impact of international trade on resource allocation, on productivity, and on economic welfare.
Salivary cortisol measurements during a medically assisted alcohol withdrawal
Authors: Keedwell Paul A. , Poon Lucia , Papadopoulos Andrew S. , Marshall E. JANE , Checkley Stuart A.
Published: July 2002

Previous studies using plasma cortisol estimations have suggested that hypothalmo‐pituitary‐axis (HPA) activation occurs in alcohol‐dependent patients during alcohol withdrawal. The present study set out to confirm this finding using salivary cortisol assays, which are a better indicator of plasma free cortisol, the fraction which exerts its physiological effects. Nine alcohol dependent patients provided four saliva samples (at 10 a.m., 2 p.m., 6 p.m. and 10 p.m.) on days 1, 3 and 7 of a medically assisted alcohol withdrawal (corresponding to 1, 3 and 7 days following the last drink, respectively).Withdrawal symptom severity, craving and mood disturbance were also measured. A group of non‐alcohol‐dependent individuals, without psychiatric or medical disorder, gave four samples at the same times on one day only. Mean daily cortisol levels in our alcohol‐dependent population, as calculated by the area under the curve (AUC), decreased significantly over time (mean AUC (nmol/l/hour) on day 1 = 149, on day 7 = 85.7, p = 0.009) and were significantly higher than controls on each day (mean AUC in controls = 28.3, p = 0.001). The cortisol response showed a similar temporal trend to withdrawal symptom severity and mood disturbance. This is consistent with previous studies measuring plasma cortisol in alcohol withdrawal. However, the magnitude of the effect in our study was greater, and in contrast to some previous studies, levels were far from normal by day 7. The comparatively low cortisol response in our one mildly dependent patient suggests that there may be a relationship between dependence severity and the size of the cortisol response to withdrawal. Salivary cortisol sampling could prove to be a useful prognostic tool, with implications for subsequent withdrawal symptom severity, mood disturbances, risk of relapse and alcohol‐related cognitive decline. There are implications for developing new treatments for alcohol withdrawal but more studies are needed.
Identification of a Novel Stage of Ribosome/Nascent Chain Association with the Endoplasmic Reticulum Membrane
Authors: Murphy Edwin C. , Zheng Tianli , Nicchitta Christopher V.
Published: July 2002

Protein translocation in the mammalian endoplasmic reticulum (ER) occurs cotranslationally and requires the binding of translationally active ribosomes to components of the ER membrane. Three candidate ribosome receptors, p180, p34, and Sec61p, have been identified in binding studies with inactive ribosomes, suggesting that ribosome binding is mediated through a receptor-ligand interaction. To determine if the binding of nascent chain-bearing ribosomes is regulated in a manner similar to inactive ribosomes, we have investigated the ribosome/nascent chain binding event that accompanies targeting. In agreement with previous reports, indicating that Sec61p displays the majority of the ER ribosome binding activity, we observed that Sec61p is shielded from proteolytic digestion by native, bound ribosomes. The binding of active, nascent chain bearing ribosomes to the ER membrane is, however, insensitive to the ribosome occupancy state of Sec61p. To determine if additional, Sec61p independent, stages of the ribosome binding reaction could be identified, ribosome/nascent chain binding was assayed as a function of RM concentration. At limiting RM concentrations, a protease resistant ribosome-membrane junction was formed, yet the nascent chain was salt extractable and cross-linked to Sec61p with low efficiency. At nonlimiting RM concentrations, bound nascent chains were protease and salt resistant and cross-linked to Sec61p with higher efficiency. On the basis of these and other data, we propose that ribosome binding to the ER membrane is a multi-stage process comprised of an initial, Sec61p independent binding event, which precedes association of the ribosome/nascent chain complex with Sec61p.
Constitutive Proteolysis of the ErbB-4 Receptor Tyrosine Kinase by a Unique, Sequential Mechanism
Authors: Vecchi Manuela , Carpenter Graham
Published: July 2002

The heregulin receptor tyrosine kinase ErbB-4 is constitutively cleaved, in the presence or absence of ligand, by an exofacial proteolytic activity producing a membrane-anchored cytoplasmic domain fragment of 80 kD. Based on selective sensitivity to inhibitors, the proteolytic activity is identified as that of a metalloprotease. The 80-kD product is tyrosine phosphorylated and retains tyrosine kinase activity. Importantly, the levels of this fragment are controlled by proteasome function. When proteasome activity is inhibited for 6 h, the kinase-active 80-kD ErbB-4 fragment accumulates to a level equivalent to 60% of the initial amount of native ErbB-4 (∼106 receptors per cell). Hence, proteasome activity is essential to prevent the accumulation of a significant level of ligand-independent, active ErbB-4 tyrosine kinase generated by metalloprotease activity. Proteasome activity, however, does not act on the native ErbB-4 receptor before the metalloprotease-mediated cleavage, as no ErbB-4 fragments accumulate when metalloprotease activity is blocked. Although no ubiquitination of the native ErbB-4 is detected, the 80-kD fragment is polyubiquitinated. The data, therefore, describe a unique pathway for the processing of growth factor receptors, which involves the sequential function of an exofacial metalloprotease and the cytoplasmic proteasome.
Apoptotic Cleavage of Cytoplasmic Dynein Intermediate Chain and P150GluedStops Dynein-Dependent Membrane Motility
Authors: Lane Jon D. , Vergnolle Maïlys A.S. , Woodman Philip G. , Allan Victoria J.
Published: July 2002

Cytoplasmic dynein is the major minus end–directed microtubule motor in animal cells, and associates with many of its cargoes in conjunction with the dynactin complex. Interaction between cytoplasmic dynein and dynactin is mediated by the binding of cytoplasmic dynein intermediate chains (CD-IC) to the dynactin subunit, p150Glued. We have found that both CD-IC and p150Glued are cleaved by caspases during apoptosis in cultured mammalian cells and in Xenopus egg extracts. Xenopus CD-IC is rapidly cleaved at a conserved aspartic acid residue adjacent to its NH2-terminal p150Glued binding domain, resulting in loss of the otherwise intact cytoplasmic dynein complex from membranes. Cleavage of CD-IC and p150Glued in apoptotic Xenopus egg extracts causes the cessation of cytoplasmic dynein–driven endoplasmic reticulum movement. Motility of apoptotic membranes is restored by recruitment of intact cytoplasmic dynein and dynactin from control cytosol, or from apoptotic cytosol supplemented with purified cytoplasmic dynein–dynactin, demonstrating the dynamic nature of the association of cytoplasmic dynein and dynactin with their membrane cargo.
Suppression of p53 function in normal human mammary epithelial cells increases sensitivity to extracellular matrix–induced apoptosis
Authors: Seewaldt Victoria L. , Mrózek Krzysztof , Sigle Randy , Dietze Eric C. , Heine Kevin , Hockenbery David M. , Hobbs Katherine B. , Caldwell L. Elizabeth
Published: July 2002

Little is known about the fate of normal human mammary epithelial cells (HMECs) that lose p53 function in the context of extracellular matrix (ECM)–derived growth and polarity signals. Retrovirally mediated expression of human papillomavirus type 16 (HPV-16) E6 and antisense oligodeoxynucleotides (ODNs) were used to suppress p53 function in HMECs as a model of early breast cancer. p53+ HMEC vector controls grew exponentially in reconstituted ECM (rECM) until day 6 and then underwent growth arrest on day 7. Ultrastructural examination of day 7 vector controls revealed acinus-like structures characteristic of normal mammary epithelium. In contrast, early passage p53− HMEC cells proliferated in rECM until day 6 but then underwent apoptosis on day 7. p53− HMEC-E6 passaged in non-rECM culture rapidly (8–10 passages), lost sensitivity to both rECM-induced growth arrest and polarity, and also developed resistance to rECM-induced apoptosis. Resistance was associated with altered expression of α3-integrin. Treatment of early passage p53− HMEC-E6 cells with either α3- or β1-integrin function-blocking antibodies inhibited rECM-mediated growth arrest and induction of apoptosis. Our results indicate that suppression of p53 expression in HMECs by HPV-16 E6 and ODNs may sensitize cells to rECM-induced apoptosis and suggest a role for the α3/β1-heterodimer in mediating apoptosis in HMECs grown in contact with rECM.
Distinct regions in the 3′ untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells
Authors: Gramolini Anthony O. , Bélanger Guy , Jasmin Bernard J.
Published: July 2002

In this study, we have sought to determine whether utrophin transcripts are targeted to a distinct subcellular compartment in skeletal muscle cells, and have examined the role of the 3′ untranslated region (UTR) in regulating the stability and localization of utrophin transcripts. Our results show that utrophin transcripts associate preferentially with cytoskeleton-bound polysomes via actin microfilaments. Because this association is not evident in myoblasts, our findings also indicate that the localization of utrophin transcripts with cytoskeleton-bound polysomes is under developmental influences. Transfection of LacZ reporter constructs containing the utrophin 3′UTR showed that this region is critical for targeting chimeric mRNAs to cytoskeleton-bound polysomes and controlling transcript stability. Deletion studies resulted in the identification of distinct regions within the 3′UTR responsible for targeting and stabilizing utrophin mRNAs. Together, these results illustrate the contribution of posttranscriptional events in the regulation of utrophin in skeletal muscle. Accordingly, these findings provide novel targets, in addition to transcriptional events, for which pharmacological interventions may be envisaged to ultimately increase the endogenous levels of utrophin in skeletal muscle fibers from Duchenne muscular dystrophy (DMD) patients.
Transforming Growth Factor β (TGF-β)-dependent Inhibition of T Helper Cell 2 (Th2)-induced Autoimmunity by Self–Major Histocompatibility Complex (MHC) Class II–specific, Regulatory CD4+ T Cell Lines
Authors: Bridoux Frank , Badou Abdallah , Saoudi Abdelhadi , Bernard Isabelle , Druet Elvira , Pasquier Régine , Druet Philippe , Pelletier Lucette
Published: July 2002

Autoreactive anti–MHC class II T cells are found in Brown Norway (BN) and Lewis (LEW) rats that receive either HgCl2 or gold salts. These T cells have a T helper cell 2 (Th2) phenotype in the former strain and are responsible for Th2-mediated autoimmunity. In contrast, T cells that expand in LEW rats produce IL-2 and prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune disease. The aim of this work was to investigate, using T cell lines derived from HgCl2-injected LEW rats (LEWHg), the effect of these autoreactive T cells on the development of Th2-mediated autoimmunity. The five LEWHg T cell lines obtained protect against Th2-mediated autoimmunity induced by HgCl2 in (LEW × BN)F1 hybrids. The lines produce, in addition to IL-2, IFN-γ and TGF-β, and the protective effect is TGF-β dependent since protection is abrogated by anti-TGF-β treatment. These results identify regulatory, TGF-β–producing, autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediated autoimmune diseases.
Elf-1 Contributes to the Function of the Complex Interleukin (IL)-2–responsive Enhancer in the Mouse IL-2 Receptor α Gene
Authors: Serdobova Irina , Pla Maria , Reichenbach Patrick , Sperisen Peter , Ghysdael Jacques , Wilson Anne , Freeman Jonathan , Nabholz Markus
Published: July 2002

Lymphocytes regulate their responsiveness to IL-2 through the transcriptional control of the IL-2Rα gene, which encodes a component of the high affinity IL-2 receptor. In the mouse IL-2Rα gene this control is exerted via two regulatable elements, a promoter proximal region, and an IL-2–responsive enhancer (IL-2rE) 1.3 kb upstream. In vitro and in vivo functional analysis of the IL-2rE in the rodent thymic lymphoma-derived, CD4−CD8− cell line PC60 demonstrated that three separate elements, sites I, II, and III, were necessary for IL-2 responsiveness; these three sites demonstrate functional cooperation. Site III contains a consensus binding motif for members of the Ets family of transcription factors. Here we demonstrate that Elf-1, an Ets-like protein, binds to site III and participates in IL-2 responsiveness. In vitro site III forms a complex with a protein constitutively present in nuclear extracts from PC60 cells as well as from normal CD4−CD8− thymocytes. We have identified this molecule as Elf-1 according to a number of criteria. The complex possesses an identical electrophoretic mobility to that formed by recombinant Elf-1 protein and is super-shifted by anti–Elf-1 antibodies. Biotinylated IL-2rE probes precipitate Elf-1 from PC60 extracts provided site III is intact and both recombinant and PC60-derived proteins bind with the same relative affinities to different mutants of site III. In addition, by introducing mutations into the core of the site III Ets-like motif and comparing the corresponding effects on the in vitro binding of Elf-1 and the in vivo IL-2rE activity, we provide strong evidence that Elf-1 is directly involved in IL-2 responsiveness. The nature of the functional cooperativity observed between Elf-1 and the factors binding sites I and II remains unresolved; experiments presented here however suggest that this effect may not require direct interactions between the proteins binding these three elements.
Regulation of Anti–double-stranded DNA B Cells in Nonautoimmune Mice: Localization to the T–B Interface of the Splenic Follicle
Authors: Mandik-Nayak Laura , Bui Anh , Noorchashm Hooman , Eaton Ashlyn , Erikson Jan
Published: July 2002

Systemic lupus erythematosus (SLE) and the MRL-lpr/lpr murine model for SLE are characterized by the presence of serum anti–double-stranded (ds)DNA antibodies (Abs), whereas nonautoimmune individuals have negligible levels of these Abs. To increase the frequency of anti-DNA B cells and identify the mechanisms involved in their regulation in nonautoimmune mice, we have used Ig transgenes (tgs). In the present study, we used the VH3H9 heavy (H) chain tg which expresses an H chain that was repeatedly isolated from anti-dsDNA Abs from MRL-lpr/lpr mice. Because the VH3H9 H chain can pair with endogenous L chains to generate anti–single-stranded DNA, anti-dsDNA, and non-DNA B cells, this allowed us to study the regulation of anti-dsDNA B cells in the context of a diverse B cell repertoire. We have identified anti-dsDNA B cells that are located at the T–B interface in the splenic follicle where they have an increased in vivo turnover rate. These anti-dsDNA B cells exhibit a unique surface phenotype suggesting developmental arrest due to antigen exposure.
Negative Selection during the Peripheral Immune Response to Antigen
Authors: Anderton Stephen M. , Radu Caius G. , Lowrey Pauline A. , Ward E. Sally , Wraith David C.
Published: July 2002

Thymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen–major histocompatibility complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 Au-restricted, acetylated NH2-terminal nonameric peptide (Ac1-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for Au. In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with the same activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications for immunotherapy and vaccine design.
Localized Gene-Specific Induction of Accessibility to V(D)j Recombination Induced by E2a and Early B Cell Factor in Nonlymphoid Cells
Authors: Goebel Peter , Janney Noel , Valenzuela Joaquín R. , Romanow William J. , Murre Cornelis , Feeney Ann J.
Published: July 2002

Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VκI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vκ locus was accessible. However, here we show that Ig loci are not opened globally but that recombination is localized. Gene families are interspersed in the DH, Vκ, and Vλ loci, and we show that certain families and individual genes undergo high levels of recombination after ectopic expression of E2A or EBF, while other families within the same locus are not induced to rearrange. Furthermore, in some families, induction of germline transcription correlates with the level of induced recombination, while in others there is no correlation, suggesting that recombination is not simply initiated by induction of germline transcription. The induced repertoire seen at 24 hours does not change significantly over time indicating the absence of many secondary rearrangements and also suggesting a direct targeting mechanism. We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments.
β2-Adrenergic Receptor Signaling Acts via No Release to Mediate Ach-Induced Activation of Atp-Sensitive K+ Current in Cat Atrial Myocytes
Authors: Wang Yong G. , Dedkova Elena N. , Steinberg Susan F. , Blatter Lothar A. , Lipsius Stephen L.
Published: July 2002

In atrial myocytes, an initial exposure to isoproterenol (ISO) acts via cAMP to mediate a subsequent acetylcholine (ACh)-induced activation of ATP-sensitive K+ current (IK,ATP). In addition, β-adrenergic receptor (β-AR) stimulation activates nitric oxide (NO) release. The present study determined whether the conditioning effect of β-AR stimulation acts via β1- and/or β2-ARs and whether it is mediated via NO signaling. 0.1 μM ISO plus ICI 118,551 (ISO-β1-AR stimulation) or ISO plus atenolol (ISO-β2-AR stimulation) both increased L-type Ca2+ current (ICa,L) markedly, but only ISO-β2-AR stimulation mediated ACh-induced activation of IK,ATP. 1 μM zinterol (β2-AR agonist) also increased ICa,L and mediated ACh-activated IK,ATP. Inhibition of NO synthase (10 μM L-NIO), guanylate cyclase (10 μM ODQ), or cAMP-PKA (50 μM Rp-cAMPs) attenuated zinterol-induced stimulation of ICa,L and abolished ACh-activated IK,ATP. Spermine-NO (100 μM; an NO donor) mimicked β2-AR stimulation, and its effects were abolished by Rp-cAMPs. Intracellular dialysis of 20 μM protein kinase inhibitory peptide (PKI) abolished zinterol-induced stimulation of ICa,L. Measurements of intracellular NO ([NO]i) using the fluorescent indicator DAF-2 showed that ISO-β2-AR stimulation or zinterol increased [NO]i. L-NIO (10 μM) blocked ISO- and zinterol-induced increases in [NO]i. ISO-β1-AR stimulation failed to increase [NO]i. Inhibition of Gi-protein by pertussis toxin significantly inhibited zinterol-mediated increases in [NO]i. Wortmannin (0.2 μM) or LY294002 (10 μM), inhibitors of phosphatidylinositol 3′-kinase (PI-3K), abolished the effects of zinterol to both mediate ACh-activated IK,ATP and stimulate [NO]i. We conclude that both β1- and β2-ARs stimulate cAMP. β2-ARs act via two signaling pathways to stimulate cAMP, one of which is mediated via Gi-protein and PI-3K coupled to NO-cGMP signaling. Only β2-ARs acting exclusively via NO signaling mediate ACh-induced activation of IK,ATP. NO signaling also contributes to β2-AR stimulation of ICa,L. The differential effects of β1- and β2-ARs can be explained by the coupling of these two β-ARs to different effector signaling pathways.
Finite element analysis of compressible and incompressible fluid-solid systems
Authors: Bermúdez Alfredo , Durán Ricardo , Rodríguez Rodolfo
Published: July 2002

This paper deals with a finite element method to solve interior fluid-structure vibration problems valid for compressible and incompressible fluids. It is based on a displacement formulation for both the fluid and the solid. The pressure of the fluid is also used as a variable for the theoretical analysis yielding a well posed mixed linear eigenvalue problem. Lowest order triangular Raviart-Thomas elements are used for the fluid and classical piecewise linear elements for the solid. Transmission conditions at the fluid-solid interface are taken into account in a weak sense yielding a nonconforming discretization. The method does not present spurious or circulation modes for nonzero frequencies. Convergence is proved and error estimates independent of the acoustic speed are given. For incompressible fluids, a convenient equivalent stream function formulation and a post-process to compute the pressure are introduced.
Motion perception: from phi to omega
Authors: Rose David , Blake Randolph
Published: July 2002

When human observers view dynamic random noise, such as television ‘snow’, through a curved or annular aperture, they experience a compelling illusion that the noise is moving smoothly and coherently around the curve (‘the omega effect’). In several series of experiments, we have investigated the conditions under which this effect occurs and the possible mechanisms that might cause it. We contrast the omega effect with ‘phi motion’, seen when an object suddenly changes position. Our conclusions are that the visual scene is first segmented into objects before a coherent velocity is assigned to the texture on each object' surface. The omega effect arises because there are motion mechanisms that deal specifically with object rotation and these interact with pattern mechanisms sensitive to curvature.
Properties of polyglutamine expansion in vitro and in a cellular model for Huntington's disease
Authors: Lunkes Astrid , Trottier Yvon , Fagart Jerôme , Schultz Patrick , Zeder-Lutz Gabrielle , Moras Dino , Mandel Jean-Louis
Published: July 2002

Eight neurodegenerative diseases have been shown to be caused by the expansion of a polyglutamine stretch in specific target proteins that lead to a gain in toxic property. Most of these diseases have some features in common. A pathological threshold of 35 to 40 glutamine residues is observed in five of the diseases. The mutated proteins (or a polyglutamine-containing subfragment) form ubiquitinated aggregates in neurons of patients or mouse models, in most cases within the nucleus. We summarize the properties of a monoclonal antibody that recognizes specifically, in a Western blot, polyglutamine stretches longer than 35 glutamine residues with an affinity that increases with polyglutamine length. This indicates that the pathological threshold observed in five diseases corresponds to a conformational change creating a pathological epitope, most probably involved in the aggregation property of the carrier protein. We also show that a fragment of a normal protein carrying 38 glutamine residues is able to aggregate into regular fibrils
in vitro
. Finally, we present a cellular model in which the induced expression of a mutated full-length huntingtin protein leads to the formation of nuclear inclusions that share many characteristics with those observed in patients: those inclusions are ubiquitinated and contain only an N-terminal fragment of huntingtin. This model should thus be useful in studying a processing step that is likely to be important in the pathogenicity of mutated huntingtin.
Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons
Authors: Postigo Antonio , Calella Anna Maria , Fritzsch Bernd , Knipper Marlies , Katz David , Eilers Andreas , Schimmang Thomas , Lewin Gary R. , Klein Rüdiger , Minichiello Liliana
Published: July 2002

Signaling by brain-derived neurotrophic factor (BDNF) via the TrkB receptor, or by neurotrophin-3 (NT3) through the TrkC receptor support distinct populations of sensory neurons. The intracellular signaling pathways activated by Trk (tyrosine kinase) receptors, which in vivo promote neuronal survival and target innervation, are not well understood. Using mice with TrkB or TrkC receptors lacking the docking site for Shc adaptors (trkBshc/shc andtrkCshc/shc mice), we show that TrkB and TrkC promote survival of sensory neurons mainly through Shc site-independent pathways, suggesting that these receptors use similar pathways to prevent apoptosis. In contrast, the regulation of target innervation appears different: in trkBshc/shc mice neurons lose target innervation, whereas in trkCshc/shc mice the surviving TrkC-dependent neurons maintain target innervation and function. Biochemical analysis indicates that phosphorylation at the Shc site positively regulates autophosphorylation of TrkB, but not of TrkC. Our findings show that although TrkB and TrkC signals mediating survival are largely similar, TrkB and TrkC signals required for maintenance of target innervation in vivo are regulated by distinct mechanisms.
Comment on “Walking a charged pith ball perpendicular to an electric field,” by P. J. Ouseph and C. L. Davis [Am. J. Phys. 69 (1), 88–90 (2001)]
Authors: Dolan Paul J.
Published: July 2002

Two geometric arguments are presented that assist in visualizing the fact that a pith ball, between two almost parallel plates, will acquire a net motion in a direction perpendicular to the electric field.
Application of thermodynamic extremum principles
Authors: Fernández-Pineda C. , Velasco S.
Published: July 2002

A simple system is used to illustrate the application of different extremum principles in thermodynamics. The system consists of an ideal gas contained in an adiabatically isolated cylinder interacting with a constant-pressure work device through an adiabatic movable piston. A kinetic model is also used to analyze the time evolution of the system toward the final equilibrium state.
Finding the right cross-correlation peak for locating sounds in multipath environments with a fourth-moment function
Authors: Spiesberger John L.
Published: July 2002

To locate calling animals in reverberant environments from recordings on widely separated receivers, a fourth-moment “Augmented-Template Correlation Function” (ATCF) helps identify which of many peaks in each cross-correlation function is that corresponding to the difference in travel times for the first arrivals (reference-lag). This peak may not be the largest. The ATCF, by providing an approximate correlation between auto- and cross-correlation functions, can be orders of magnitude more efficient in selecting the reference-lag than the alternative of randomly selecting peaks. The ATCF’s efficacy increases with the number of paths and their signal-to-noise ratios.
Seismic properties of Asian elephant (Elephas maximus) vocalizations and locomotion
Authors: O’Connell-Rodwell C. E. , Arnason B. T. , Hart L. A.
Published: July 2002

Seismic and acoustic data were recorded simultaneously from Asian elephants (Elephas maximus) during periods of vocalizations and locomotion. Acoustic and seismic signals from rumbles were highly correlated at near and far distances and were in phase near the elephant and were out of phase at an increased distance from the elephant. Data analyses indicated that elephant generated signals associated with rumbles and “foot stomps” propagated at different velocities in the two media, the acoustic signals traveling at 309 m/s and the seismic signals at 248–264 m/s. Both types of signals had predominant frequencies in the range of 20 Hz. Seismic signal amplitudes considerably above background noise were recorded at 40 m from the generating elephants for both the rumble and the stomp. Seismic propagation models suggest that seismic waveforms from vocalizations are potentially detectable by instruments at distances of up to 16 km, and up to 32 km for locomotion generated signals. Thus, if detectable by elephants, these seismic signals could be useful for long distance communication.
Wave localization on a submerged cylindrical shell with rib aperiodicity
Authors: Marcus Martin H. , Houston Brian H. , Photiadis Douglas M.
Published: July 2002

The results of a numerical study of vibration localization due to stiffener variability in a framed shell are reported. An axisymmetric finite element (FE)–infinite element model is used to obtain predictions in good general agreement with previously reported experimental results. Over the frequency band of this study, up to three times the ring frequency, two structural resonances dominate the vibratory response of the shell for high circumferential orders (n>10). Localization is shown to be linked to the sensitivity of the local resonance frequencies of the system to specific geometrical parameters. Specifically, rib thickness variations strongly affect the first pass band, while rib spacing variations strongly affect the second pass band.
Acoustic radiation from bowed violins
Authors: Wang Lily M. , Burroughs Courtney B.
Published: July 2002

Near-field acoustic holography (NAH) is applied to visualize the acoustic radiation from bowed violins across a frequency range from 294 Hz to 3 kHz. These visualizations are employed to localize regions of acoustic radiation from surfaces of violins. Three violins were tested: a common student instrument by Scherl and Roth; Hutchins violin SUS295, which has been the subject of many previous investigations; and a Hutchins mezzo violin from the Violin Octet set of instruments, which is longer, broader, and thinner than a standard instrument. The violins were bowed continuously with an open-frame mechanical bowing machine, while NAH measurements were made on four planes surrounding the instrument. Mappings of the acoustic intensity are presented that show locations of maximum radiation at low and high frequencies with a spatial resolution smaller than the acoustic wavelength. Comparisons are made of the radiation patterns between the two conventional instruments and the mezzo violin. Radiation patterns from SUS295 at frequencies near to known modal responses are also presented.
Application of multidimensional scaling to subjective evaluation of coded speech
Authors: Hall Joseph L.
Published: July 2002

We present results from a pilot study directed at developing an anchorable subjective speech quality test. The test uses multidimensional scaling techniques to obtain quantitative information about the perceptual attributes of speech. In the first phase of the study, subjects ranked perceptual distances between samples of speech produced by two different talkers, one male and one female, processed by a variety of codecs. The resulting distance matrices were processed to obtain, for each talker, a stimulus space for the various speech samples. This stimulus space has the properties that distances between stimuli in this space correspond to perceptual distances between stimuli and that the dimensions of this space correspond to attributes used by the subjects in determining perceptual distances. Mean opinion scores (MOS) scores obtained in an earlier study were found to be highly correlated with position in the stimulus space, and the three dimensions of the stimulus space were found to have identifiable physical and perceptual correlates. In the second phase of the study, we developed techniques for fitting speech generated by a new codec under investigation into a previously established stimulus space. The user is provided with a collection of speech samples and with the stimulus space for these speech samples as determined by a large-scale listening test. The user then carries out a much smaller listening test to determine the position of the new stimulus in the previously established stimulus space. This system is anchorable, so that different versions of a codec under development can be compared directly, and it provides more detailed information than the single number provided by MOS testing. We suggest that this information could be used to advantage in algorithm development and in development of objective measures of speech quality.
Sound scattering from a moving turbulent medium
Authors: Ye Zhen
Published: July 2002

This paper studies sound scattering by a moving turbulent atmospheric medium, following the work of Clifford and Brown [J. Acoust. Soc. Am. 55, 929–933 (1974)]. A formula for the sound scattering cross section is derived using the Galilean transformation and Snell’s law of wave refraction. Effects of the mean flow on the scattering process are examined. Numerical examples show that, unlike the zero-flow case, there exists a nonzero cross section at right scattering angles for scattering from both velocity and temperature fluctuations. More importantly, the mean flow may give rise to significant contributions to the backscattering from turbulent eddies, in contrast to the zero-flow case and the previous results.
Geoacoustic parameters for high-frequency bottom scattering
Authors: Tang Dajun
Published: July 2002

In order to model scattering of high-frequency sound owing to sediment volume inhomogeneities, several geoacoustic parameters are needed. If the sediment is modeled as a fluid medium, which is believed appropriate for most sediment types, in addition to mean sound-speed profile, mean density profile, and attenuation coefficient as a function of frequency, one needs a set of parameters controlling the stochastic nature of the scatterers. For the minimum, one needs the spatial autocorrelation functions of sound speed and density, and cross-correlation function between sound speed and density. In this presentation, first numerical simulations of volume scattering will be given to highlight the needs of the geoacoustic parameters. Then, in situ and laboratory measurements as well as modeling of the stochastic geoacoustic parameters will be discussed.
Acoustic phase conjugation by nonlinear piezoelectricity. I. Principle and basic experiments
Authors: Ohno Masahiro , Yamamoto Ken , Kokubo Akira , Sakai Keiji , Takagi Kenshiro
Published: July 2002

The principle and the basic experimental results of the acoustic phase conjugation by nonlinear piezoelectricity are described. Acoustic phase conjugate waves at frequency ω are generated as a result of the interaction between incident acoustic waves at ω and pump electric fields at 2ω. An original explanation based on the modulation of sound velocity by the electric field together with the concept of time grating is given. Coupling equations for the PZT ceramics as a nonlinear material are derived. Experimental results of the sound velocity modulation and the phase conjugate generation in nonlinear piezoelectric PZT ceramics are shown. Amplitude reflectivity of the phase conjugation was 23% for the acoustic incidence at 10 MHz.
A zero-order energy finite-element method (EFEM) and its similarity to SEA
Authors: Bernhard Robert J. , Wang Shuo
Published: July 2002

In this investigation it was found that a simple zero-order EFEM procedure using piecewise constant elements has essentially the same form as an SEA approximation. Thus, a relationship between SEA and EFEM can be established and the approximations of the two methods compared. The derivation of the zero-order EFEM approximation also indicates potential new formulations of coupling loss factors for damped and strongly coupled systems. These coupling loss factor formulations were used and verified against analytical solutions with both EFEM and SEA software. The predicted results converge to the analytical result as more elements are used.
Echo suppression in the horizontal and median sagittal planes
Authors: Rakerd Brad , Hartmann William M. , Hsu Joy
Published: July 2002

Experiments were performed to measure two kinds of suppression threshold for running speech: echo threshold, defined here as the minimum level at which it was possible to detect that an echo was present, and masked threshold, defined as the minimum level at which it was possible to detect that a lagging sound was present at all. Both thresholds were measured using a geometry in which sound sources and reflections were distributed over the horizontal plane (left, front, and right locations) and a geometry in which they were distributed over the median sagittal plane (front, overhead, and rear locations). The predominant sound localization cues are different for these two geometries, and the experiments measured the consequences of this difference for suppression. Echo thresholds were found to have a comparable dependence on the delay of the lagging sound for the horizontal and median sagittal planes. Masked thresholds, which were systematically 8–15 dB lower than echo thresholds, also showed a comparable dependence on delay for the two planes. Overall, these results support the idea that echo suppression is functionally similar whether locations are cued by interaural differences in time and intensity, or by spectral features introduced by the head-related transfer function.
Time reversal in a waveguide: Study of the temporal and spatial focusing
Authors: Roux Philippe , Fink Mathias
Published: July 2002

Temporal and spatial focusing properties of time-reversal mirrors (TRMs) are studied in a waveguide. The experiments are done using an ultrasonic TRM in an idealized waveguide. The width of the focal spot, and the spatial and temporal sidelobe levels are experimentally and numerically analyzed with respect to the characteristics of the waveguide-TRM system. An algorithm is developed to compute directly in the time domain the time-reversed field. This algorithm is based on the application of the mirror theorem to both the source and the TRM placed in the waveguide. Because time reversal is a stable and robust process, some of the ultrasonic results can be extended to ocean acoustics. Applications to underwater acoustic transmissions as well as ultrasonic medical imaging are discussed.
The psychomechanics of real and simulated sound sources
Authors: McAdams Stephen
Published: July 2002

Recent advances in the physical acoustics of musical instruments and the development of physically based signal-processing models have opened a new path to the psychological investigation of sound-source perception. In particular, it is now possible to rigorously and systematically study the perceptual results of changes in physical properties that affect the mechanics of a musical instrument. As a first step in this direction, experiments from several laboratories have been conducted on the recognition and classification of sounds produced by real percussive instruments (bars and plates). These results show a surprising sensitivity to geometric properties. However, this sensitivity depends on the materials composing the sources and on the kinds of judgments listeners have to make. Other experiments have been performed on the perceptual dissimilarities among sounds produced by physical models of bars and plates whose material properties such as density, damping, and elasticity are varied. The results also show a very strong sensitivity of listeners to these latter mechanical dimensions, with the relevant perceptual dimensions often being transformations of the mechanical ones. The scope of the psychoacoustics of sound signals appears to be widening to include what might be called the ‘‘psychomechanics’’ of sound sources.
Combustion and acoustic waves—A damaging combination
Authors: Dowling Ann
Published: July 2002

Instability can occur whenever combustion takes place within an acoustic resonator—essentially because the unsteady combustion generates sound, while the resulting acoustic waves perturb the combustion still further. Many combustors have been found to be susceptible to self-excited oscillations: currently the occurrence of instability in lean premixed combustion systems is proving to be a major technological challenge. By burning lean premixed and prevaporized, it is possible to reduce chemical emissions significantly. Unfortunately, these are just the conditions that make a flame particularly sensitive to acoustic disturbances. Coupling between the rate of heat release and the sound waves can lead to self-excited oscillations, and the resulting pressure oscillations and/or enhanced heat transfer may cause structural damage. Modeling of combustion instability requires application of ideas from acoustics, combustion, and systems engineering. A wave analysis will be presented which is useful to describe sound generation in complex geometries with mean flow. The complementary roles of low-order models for unsteady combustion and of computational fluid dynamics (CFD) will be discussed. Particular emphasis will be placed on the effective integration of CFD and acoustic modeling. These solution methods will be illustrated by investigation of oscillations in generic premixed ducted flames and in aeroengine combustors.