bluuebunny/crossref_metadata_2025 huggingface dataset:
The DHC1b (DHC2) Isoform of Cytoplasmic Dynein Is Required for Flagellar Assembly
Authors: Pazour Gregory J. , Dickert Bethany L. , Witman George B.
Published: July 2002

Dyneins are microtubule-based molecular motors involved in many different types of cell movement. Most dynein heavy chains (DHCs) clearly group into cytoplasmic or axonemal isoforms. However, DHC1b has been enigmatic. To learn more about this isoform, we isolated Chlamydomonas cDNA clones encoding a portion of DHC1b, and used these clones to identify a Chlamydomonas cell line with a deletion mutation in DHC1b. The mutant grows normally and appears to have a normal Golgi apparatus, but has very short flagella. The deletion also results in a massive redistribution of raft subunits from a peri-basal body pool (Cole, D.G., D.R. Diener, A.L. Himelblau, P.L. Beech, J.C. Fuster, and J.L. Rosenbaum. 1998. J. Cell Biol. 141:993–1008) to the flagella. Rafts are particles that normally move up and down the flagella in a process known as intraflagellar transport (IFT) (Kozminski, K.G., K.A. Johnson, P. Forscher, and J.L. Rosenbaum. 1993. Proc. Natl. Acad. Sci. USA. 90:5519–5523), which is essential for assembly and maintenance of flagella. The redistribution of raft subunits apparently occurs due to a defect in the retrograde component of IFT, suggesting that DHC1b is the motor for retrograde IFT. Consistent with this, Western blots indicate that DHC1b is present in the flagellum, predominantly in the detergent- and ATP-soluble fractions. These results indicate that DHC1b is a cytoplasmic dynein essential for flagellar assembly, probably because it is the motor for retrograde IFT.
Exogenous Expression of β-Catenin Regulates Contact Inhibition, Anchorage-Independent Growth, Anoikis, and Radiation-Induced Cell Cycle Arrest
Authors: Orford Keith , Orford Caroline C. , Byers Stephen W.
Published: July 2002

β-Catenin is an important regulator of cell–cell adhesion and embryonic development that associates with and regulates the function of the LEF/TCF family of transcription factors. Mutations of β-catenin and the tumor suppressor gene, adenomatous polyposis coli, occur in human cancers, but it is not known if, and by what mechanism, increased β-catenin causes cellular transformation. This study demonstrates that modest overexpression of β-catenin in a normal epithelial cell results in cellular transformation. These cells form colonies in soft agar, survive in suspension, and continue to proliferate at high cell density and following γ-irradiation. Endogenous cytoplasmic β-catenin levels and signaling activity were also found to oscillate during the cell cycle. Taken together, these data demonstrate that β-catenin functions as an oncogene by promoting the G1 to S phase transition and protecting cells from suspension-induced apoptosis (anoikis).
Pak-Family Kinases Regulate Cell and Actin Polarization Throughout the Cell Cycle of Saccharomyces cerevisiae
Authors: Holly Stephen P. , Blumer Kendall J.
Published: July 2002

During the cell cycle of the yeast Saccharomyces cerevisiae, the actin cytoskeleton and cell surface growth are polarized, mediating bud emergence, bud growth, and cytokinesis. We have determined whether p21-activated kinase (PAK)-family kinases regulate cell and actin polarization at one or several points during the yeast cell cycle. Inactivation of the PAK homologues Ste20 and Cla4 at various points in the cell cycle resulted in loss of cell and actin cytoskeletal polarity, but not in depolymerization of F-actin. Loss of PAK function in G1 depolarized the cortical actin cytoskeleton and blocked bud emergence, but allowed isotropic growth and led to defects in septin assembly, indicating that PAKs are effectors of the Rho–guanosine triphosphatase Cdc42. PAK inactivation in S/G2 resulted in depolarized growth of the mother and bud and a loss of actin polarity. Loss of PAK function in mitosis caused a defect in cytokinesis and a failure to polarize the cortical actin cytoskeleton to the mother-bud neck. Cla4–green fluorescent protein localized to sites where the cortical actin cytoskeleton and cell surface growth are polarized, independently of an intact actin cytoskeleton. Thus, PAK family kinases are primary regulators of cell and actin cytoskeletal polarity throughout most or all of the yeast cell cycle. PAK-family kinases in higher organisms may have similar functions.
The Tetraspan Molecule Cd151, a Novel Constituent of Hemidesmosomes, Associates with the Integrin α6β4 and May Regulate the Spatial Organization of Hemidesmosomes
Authors: Sterk Lotus M.Th. , Geuijen Cecile A.W. , Oomen Lauran C.J.M. , Calafat Jero , Janssen Hans , Sonnenberg Arnoud
Published: July 2002

CD151 is a cell surface protein that belongs to the tetraspan superfamily. It associates with other tetraspan molecules and certain integrins to form large complexes at the cell surface. CD151 is expressed by a variety of epithelia and mesenchymal cells. We demonstrate here that in human skin CD151 is codistributed with α3β1 and α6β4 at the basolateral surface of basal keratinocytes. Immunoelectron microscopy showed that CD151 is concentrated in hemidesmosomes. By immunoprecipitation from transfected K562 cells, we established that CD151 associates with α3β1 and α6β4. In β4-deficient pyloric atresia associated with junctional epidermolysis bullosa (PA-JEB) keratinocytes, CD151 and α3β1 are clustered together at the basal cell surface in association with patches of laminin-5. Focal adhesions are present at the periphery of these clusters, connected with actin filaments, and they contain both CD151 and α3β1. Transient transfection studies of PA-JEB cells with β4 revealed that the integrin α6β4 becomes incorporated into the α3β1-CD151 clusters where it induces the formation of hemidesmosomes. As a result, the amount of α3β1 in the clusters diminishes and the protein becomes restricted to the peripheral focal adhesions. Furthermore, CD151 becomes predominantly associated with α6β4 in hemidesmosomes, whereas its codistribution with α3β1 in focal adhesions becomes partial. The localization of α6β4 in the pre-hemidesmosomal clusters is accompanied by a strong upregulation of CD151, which is at least partly due to increased cell surface expression. Using β4 chimeras containing the extracellular and transmembrane domain of the IL-2 receptor and the cytoplasmic domain of β4, we found that for recruitment of CD151 into hemidesmosomes, the β4 subunit must be associated with α6, confirming that integrins associate with tetraspans via their α subunits. CD151 is the only tetraspan identified in hemidesmosomal structures. Others, such as CD9 and CD81, remain diffusely distributed at the cell surface.

In conclusion, we show that CD151 is a major component of (pre)-hemidesmosomal structures and that its recruitment into hemidesmosomes is regulated by the integrin α6β4. We suggest that CD151 plays a role in the formation and stability of hemidesmosomes by providing a framework for the spatial organization of the different hemidesmosomal components.
Hsp90
Authors: Young Jason C. , Moarefi Ismail , Hartl F. Ulrich
Published: July 2002

Hsp90 is unique among molecular chaperones. The majority of its known substrates are signal transduction proteins, and recent work indicates that it uses a novel protein-folding strategy.
Intraflagellar transport balances continuous turnover of outer doublet microtubules
Authors: Marshall Wallace F. , Rosenbaum Joel L.
Published: July 2002

A central question in cell biology is how cells determine the size of their organelles. Flagellar length control is a convenient system for studying organelle size regulation. Mechanistic models proposed for flagellar length regulation have been constrained by the assumption that flagella are static structures once they are assembled. However, recent work has shown that flagella are dynamic and are constantly turning over. We have determined that this turnover occurs at the flagellar tips, and that the assembly portion of the turnover is mediated by intraflagellar transport (IFT). Blocking IFT inhibits the incorporation of tubulin at the flagellar tips and causes the flagella to resorb. These results lead to a simple steady-state model for flagellar length regulation by which a balance of assembly and disassembly can effectively regulate flagellar length.
Phosphorylation of the AP2 μ subunit by AAK1 mediates high affinity binding to membrane protein sorting signals
Authors: Ricotta Doris , Conner Sean D. , Schmid Sandra L. , von Figura Kurt , Höning Stefan
Published: July 2002

During receptor-mediated endocytosis, AP2 complexes act as a bridge between the cargo membrane proteins and the clathrin coat by binding to sorting signals via the μ2 subunit and to clathrin via the β subunit. Here we show that binding of AP2 to sorting signals in vitro is regulated by phosphorylation of the μ2 subunit of AP2. Phosphorylation of μ2 enhances the binding affinity of AP2 for sorting motifs as much as 25-fold compared with dephosphorylated AP2. The recognition of sorting signals was not affected by the phosphorylation status of the α or β2 subunit, suggesting that phosphorylation of μ2 is critical for regulation of AP2 binding to sorting signals. Phosphorylation of μ2 occurs at a single threonine residue (Thr-156) and is mediated by the newly discovered adaptor-associated kinase, AAK1, which copurifies with AP2. We propose that phosphorylation of the AP2 μ2 subunit by AAK1 ensures high affinity binding of AP2 to sorting signals of cargo membrane proteins during the initial steps of receptor-mediated endocytosis.
An Antagonist of Monocyte Chemoattractant Protein 1 (MCP-1) Inhibits Arthritis in the MRL-lpr Mouse Model
Authors: Gong Jiang-Hong , Ratkay Leslie G. , Waterfield J. Douglas , Clark-Lewis Ian
Published: July 2002

An antagonist of human monocyte chemoattractant protein (MCP)-1, which consists of MCP-1(9-76), had previously been characterized and shown to inhibit MCP-1 activity in vitro. To test the hypothesis that, by inhibiting endogenous MCP-1, the antagonist has antiinflammatory activity in vivo, we examined its effect in the MRL-lpr mouse model of arthritis. This strain spontaneously develops a chronic inflammatory arthritis that is similar to human rheumatoid arthritis. Daily injection of the antagonist, MCP-1(9-76), prevented the onset of arthritis as monitored by measuring joint swelling and by histopathological evaluation of the joints. In contrast, controls treated with native MCP-1 had enhanced arthritis symptoms, indicating that the inhibitory effect is specific to the antagonist. In experiments where the antagonist was given only after the disease had already developed, there was a marked reduction in symptoms and histopathology, although individuals varied in the magnitude of the response. The mechanism of inhibition of disease is not known, although the results suggest that it could be more complex than the competitive inhibition of ligand binding that is observed in vitro. The demonstration of the beneficial effects of an MCP-1 antagonist in arthritis suggests that chemokine receptor antagonists could have therapeutic application in inflammatory diseases.
Development of a Natural Model of Cutaneous Leishmaniasis: Powerful Effects of  Vector Saliva and Saliva Preexposure on the Long-Term Outcome of Leishmania major Infection in the Mouse Ear Dermis
Authors: Belkaid Yasmine , Kamhawi Shaden , Modi Govind , Valenzuela Jesus , Noben-Trauth Nancy , Rowton Edgar , Ribeiro José , Sacks David L.
Published: July 2002

We have developed a model of cutaneous leishmaniasis due to Leishmania major that seeks to mimic the natural conditions of infection. 1,000 metacyclic promastigotes were coinoculated with a salivary gland sonicate (SGS) obtained from a natural vector, Phlebotomus papatasii, into the ear dermis of naive mice or of mice preexposed to SGS. The studies reveal a dramatic exacerbating effect of SGS on lesion development in the dermal site, and a complete abrogation of this effect in mice preexposed to salivary components. In both BALB/c and C57Bl/6 (B/6) mice, the dermal lesions appeared earlier, were more destructive, and contained greater numbers of parasites after infection in the presence of SGS. Furthermore, coinoculation of SGS converted B/6 mice into a nonhealing phenotype. No effect of SGS was seen in either IL-4– deficient or in SCID mice. Disease exacerbation in both BALB/c and B/6 mice was associated with an early (6 h) increase in the frequency of epidermal cells producing type 2 cytokines. SGS did not elicit type 2 cytokines in the epidermis of mice previously injected with SGS. These mice made antisaliva antibodies that were able to neutralize the ability of SGS to enhance infection and to elicit IL-4 and IL-5 responses in the epidermis. These results are the first to suggest that for individuals at risk of vector-borne infections, history of exposure to vector saliva might influence the outcome of exposure to transmitted parasites.
Antigen-dependent CD28 Signaling Selectively Enhances Survival and Proliferation in Genetically Modified Activated Human Primary T Lymphocytes
Authors: Krause Anja , Guo Hong-Fen , Latouche Jean-Baptiste , Tan Cuiwen , Cheung Nai-Kong  V. , Sadelain Michel
Published: July 2002

Most tumor cells function poorly as antigen-presenting cells in part because they do not express costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for GD2, a ganglioside overexpressed on the surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors. Recognition of GD2 was provided by a single-chain antibody derived from the GD2-specific monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides CD28 signaling upon specific recognition of the GD2 antigen on tumor cells. Human primary T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8+ lymphocytes expressing 3G6-CD28 are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with GD2. Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.
Recognition of the Class Ib Molecule Qa-1b by Putative Activating Receptors Cd94/Nkg2c and Cd94/Nkg2e on Mouse Natural Killer Cells
Authors: Vance Russell E. , Jamieson Amanda M. , Raulet David H.
Published: July 2002

The heterodimeric CD94/NKG2A receptor, expressed by mouse natural killer (NK) cells, transduces inhibitory signals upon recognition of its ligand, Qa-1b, a nonclassical major histocompatibility complex class Ib molecule. Here we clone and express two additional receptors, CD94/NKG2C and CD94/NKG2E, which we show also bind to Qa-1b. Within their extracellular carbohydrate recognition domains, NKG2C and NKG2E share extensive homology with NKG2A (93–95% amino acid similarity); however, NKG2C/E receptors differ from NKG2A in their cytoplasmic domains (only 33% similarity) and contain features that suggest that CD94/NKG2C and CD94/NKG2E may be activating receptors. We employ a novel blocking anti-NKG2 monoclonal antibody to provide the first direct evidence that CD94/NKG2 molecules are the only Qa-1b receptors on NK cells. Molecular analysis reveals that NKG2C and NKG2E messages are extensively alternatively spliced and ∼20-fold less abundant than NKG2A message in NK cells. The organization of the mouse Cd94/Nkg2 gene cluster, presented here, shows striking similarity with that of the human, arguing that the entire CD94/NKG2 receptor system is relatively primitive in origin. Analysis of synonymous substitution frequencies suggests that within a species, NKG2 genes may maintain similarities with each other by concerted evolution, possibly involving gene conversion–like events. These findings have implications for understanding NK cells and also raise new possibilities for the role of Qa-1 in immune responses.
Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation
Authors: Read Simon , Malmström Vivianne , Powrie Fiona
Published: July 2002

It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25+CD45RBlowCD4+) as those that control autoimmunity. Previous studies have failed to identify how CD25+ Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor β. Strikingly, constitutive expression of CTLA-4 among CD4+ cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.
Essential Role of Signal Transducer and Activator of Transcription (Stat)5a but Not Stat5b for Flt3-Dependent Signaling
Authors: Zhang Shuli , Fukuda Seiji , Lee Younghee , Hangoc Giao , Cooper Scott , Spolski Rosanne , Leonard Warren J. , Broxmeyer Hal E.
Published: July 2002

The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic stem and progenitor cells. Although some post-receptor signaling events of Flt3 have been characterized, the involvement of the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in Flt3 signaling has not been thoroughly evaluated. To this aim, we examined whether Flt3 activates the Jak/Stat pathway in Baf3/Flt3 cells, a line stably expressing human Flt3 receptor. Stat5a, but not Stats 1–4, 5b, or 6, was potently activated by Flt3 ligand (FL) stimulation. Interestingly, FL did not activate any Jaks. Activation of Stat5a required the kinase activity of Flt3. A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a−/− mice, but did stimulate/costimulate proliferation of these cells from Stat5a+/+, Stat5b−/−, and Stat5b+/+ mice. Thus, Stat5a is essential for at least certain effects of FL. Moreover, our data confirm that Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.
Conditional Vascular Cell Adhesion Molecule 1 Deletion in Mice
Authors: Koni Pandelakis A. , Joshi Sunil K. , Temann Ulla-Angela , Olson Dian , Burkly Linda , Flavell Richard A.
Published: July 2002

We generated vascular cell adhesion molecule (VCAM)-1 “knock-in” mice and Cre recombinase transgenic mice to delete the VCAM-1 gene (vcam-1) in whole mice, thereby overcoming the embryonic lethality seen with conventional vcam-1–deficient mice. vcam-1 knock-in mice expressed normal levels of VCAM-1 but showed loss of VCAM-1 on endothelial and hematopoietic cells when interbred with a “TIE2Cre” transgene. Analysis of peripheral blood from conditional vcam-1–deficient mice revealed mild leukocytosis, including elevated immature B cell numbers. Conversely, the bone marrow (BM) had reduced immature B cell numbers, but normal numbers of pro-B cells. vcam-1–deficient mice also had reduced mature IgD+ B and T cells in BM and a greatly reduced capacity to support short-term migration of transferred B cells, CD4+ T cells, CD8+ T cells, and preactivated CD4+ T cells to the BM. Thus, we report an until now unappreciated dominant role for VCAM-1 in lymphocyte homing to BM.
Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor β1
Authors: Lee Chun Geun , Homer Robert J. , Zhu Zhou , Lanone Sophie , Wang Xiaoman , Koteliansky Victor , Shipley J. Michael , Gotwals Philip , Noble Paul , Chen Qingsheng , Senior Robert M. , Elias Jack A.
Published: July 2002

Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-β. To test this hypothesis we compared the regulation of TGF-β in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-β1 production in transgenic animals and macrophages were the major site of TGF-β1 production and deposition in these tissues. IL-13 also activated TGF-β1 in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-β–binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-β1 activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13–induced fibrosis was also significantly ameliorated by treatment with the TGF-β antagonist soluble TGFβR-Fc (sTGFβR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-β1 in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9–dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-β pathway.
c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Have Distinct Roles in CD8+ T Cell Activation
Authors: Conze Dietrich , Krahl Troy , Kennedy Norman , Weiss Linda , Lumsden Joanne , Hess Patricia , Flavell Richard A. , Le Gros Graham , Davis Roger J. , Rincón Mercedes
Published: July 2002

The c-Jun NH2-terminal kinase (JNK) signaling pathway is induced by cytokines and stress stimuli and is implicated in cell death and differentiation, but the specific function of this pathway depends on the cell type. Here we examined the role of JNK1 and JNK2 in CD8+ T cells. Unlike CD4+ T cells, the absence of JNK2 causes increased interleukin (IL)-2 production and proliferation of CD8+ T cells. In contrast, JNK1-deficient CD8+ T cells are unable to undergo antigen-stimulated expansion in vitro, even in the presence of exogenous IL-2. The hypoproliferation of these cells is associated with impaired IL-2 receptor α chain (CD25) gene and cell surface expression. The reduced level of nuclear activating protein 1 (AP-1) complexes in activated JNK1-deficient CD8+ T cells can account for the impaired IL-2 receptor α chain gene expression. Thus, JNK1 and JNK2 play different roles during CD8+ T cell activation and these roles differ from those in CD4+ T cells.
Imperatoxin A Induces Subconductance States in Ca2+ Release Channels (Ryanodine Receptors) of Cardiac and Skeletal Muscle
Authors: Tripathy Ashutosh , Resch Wolfgang , Le Xu  , Valdivia Hector H. , Meissner Gerhard
Published: July 2002

Single-channel and [3H]ryanodine binding experiments were carried out to examine the effects of imperatoxin activator (IpTxa), a 33 amino acid peptide isolated from the venom of the African scorpion Pandinus imperator, on rabbit skeletal and canine cardiac muscle Ca2+ release channels (CRCs). Single channel currents from purified CRCs incorporated into planar lipid bilayers were recorded in 250 mM KCl media. Addition of IpTxa in nanomolar concentration to the cytosolic (cis) side, but not to the lumenal (trans) side, induced substates in both ryanodine receptor isoforms. The substates displayed a slightly rectifying current–voltage relationship. The chord conductance at −40 mV was ∼43% of the full conductance, whereas it was ∼28% at a holding potential of +40 mV. The substate formation by IpTxa was voltage and concentration dependent. Analysis of voltage and concentration dependence and kinetics of substate formation suggested that IpTxa reversibly binds to the CRC at a single site in the voltage drop across the channel. The rate constant for IpTxa binding to the skeletal muscle CRC increased e-fold per +53 mV and the rate constant of dissociation decreased e-fold per +25 mV applied holding potential. The effective valence of the reaction leading to the substate was ∼1.5. The IpTxa binding site was calculated to be located at ∼23% of the voltage drop from the cytosolic side. IpTxa induced substates in the ryanodine-modified skeletal CRC and increased or reduced [3H]ryanodine binding to sarcoplasmic reticulum vesicles depending on the level of channel activation. These results suggest that IpTxa induces subconductance states in skeletal and cardiac muscle Ca2+ release channels by binding to a single, cytosolically accessible site different from the ryanodine binding site.
Nonselfadjoint operators generated by the equation of a nonhomogeneous damped string
Authors: Shubov Marianna
Published: July 2002

We consider a one-dimensional wave equation, which governs the vibrations of a damped string with spatially nonhomogeneous density and damping coefficients. We introduce a family of boundary conditions depending on a complex parameter

h
h

. Corresponding to different values of

h
h

, the problem describes either vibrations of a finite string or propagation of elastic waves on an infinite string. Our main object of interest is the family of non-selfadjoint operators

A
h

A_h

in the energy space of two-component initial data. These operators are the generators of the dynamical semigroups corresponding to the above boundary-value problems. We show that the operators

A
h

A_h

are dissipative, simple, maximal operators, which differ from each other by rank-one perturbations. We also prove that the operator

A
1

(
h
=
1
)

A_1 (h=1)

coincides with the generator of the Lax-Phillips semigroup, which plays an important role in the aforementioned scattering problem. The results of this work are applied in our two forthcoming papers both to the proof of the Riesz basis property of the eigenvectors and associated vectors of the operators

A
h

A_h

and to establishing the exact and approximate controllability of the system governed by the damped wave equation.
When encodong yields remembering: insights from event-related neuroimaging
Authors: Wagner Anthony D. , Koutstaal Wilma , Schacter Daniel L.
Published: July 2002

To understand human memory, it is important to determine why some experiences are remembered whereas others are forgotten. Until recently, insights into the neural bases of human memory encoding, the processes by which information is transformed into an enduring memory trace, have primarily been derived from neuropsychological studies of humans with select brain lesions. The advent of functional neuroimaging methods, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), has provided a new opportunity to gain additional understanding of how the brain supports memory formation. Importantly, the recent development of event–related fMRI methods now allows for examination of trial–by–trial differences in neural activity during encoding and of the consequences of these differences for later remembering. In this review, we consider the contributions of PET and fMRI studies to the understanding of memory encoding, placing a particular emphasis on recent event–related fMRI studies of the Dm effect: that is, differences in neural activity during encoding that are related to differences in subsequent memory. We then turn our attention to the rich literature on the Dm effect that has emerged from studies using event–related potentials (ERPs). It is hoped that the integration of findings from ERP studies, which offer higher temporal resolution, with those from event–related fMRI studies, which offer higher spatial resolution, will shed new light on when and why encoding yields subsequent remembering.
Abnormalities in the awareness and control of action
Authors: Frith Christopher D. , Blakemore Sarah-Jayne , Wolpert Daniel M.
Published: July 2002

Much of the functioning of the motor system occurs without awareness. Nevertheless, we are aware of some aspects of the current state of the system and we can prepare and make movements in the imagination. These mental representations of the actual and possible states of the system are based on two sources: sensory signals from skin and muscles, and the stream of motor commands that have been issued to the system. Damage to the neural substrates of the motor system can lead to abnormalities in the awareness of action as well as defects in the control of action. We provide a framework for understanding how these various abnormalities of awareness can arise. Patients with phantom limbs or with anosognosia experience the illusion that they can move their limbs. We suggest that these representations of movement are based on streams of motor commands rather than sensory signals. Patients with utilization behaviour or with delusions of control can no longer properly link their intentions to their actions. In these cases the impairment lies in the representation of intended movements. The location of the neural damage associated with these disorders suggests that representations of the current and predicted state of the motor system are in parietal cortex, while representations of intended actions are found in prefrontal and premotor cortex.
Molecular definition of the germinal centre stage of B–cell differentiation
Authors: Ma Chi , Staudt Louis M.
Published: July 2002

Genomic–scale gene expression analysis provides views of biological processes as a whole that are difficult to obtain using traditional single–gene experimental approaches. In the case of differentiating systems, gene expression profiling can define a stage of differentiation by the characteristic expression of hundreds of genes. Using specialized DNA microarrays termed ‘Lymphochips’, gene expression during mature B–cell differentiation has been defined. Germinal centre B cells represent a stage of differentiation that can be defined by a gene expression signature that is not shared by other highly proliferative B–cell populations such as mitogenically activated peripheral blood B cells. The germinal centre gene expression signature is maintained to a significant degree in lymphoma cell lines derived from this stage of differentiation, demonstrating that this gene expression programme does not require ongoing interactions with other germinal centre cell types. Analysis of representative cDNA libraries prepared from resting and activated peripheral blood B cells, germinal centre centroblasts, centrocytes and tonsillar memory B cells has confirmed and extended the results of DNA microarray gene expression analysis.
Electron spectra derived from depth dose distributions
Authors: Faddegon B. A. , Blevis I.
Published: July 2002

The technique of extracting electron energy spectra from measured distributions of dose along the central axis of clinical electron beams is explored in detail. Clinical spectra measured with this simple spectroscopy tool are shown to be sufficient in accuracy and resolution for use in Monte Carlo treatment planning. A set of monoenergetic depth dose curves of appropriate energy spacing, precalculated with Monte Carlo for a simple beam model, are unfolded from the measured depth dose curve. The beam model is comprised of a point electron and photon source placed in vacuum with a source‐to‐surface distance of 100 cm. Systematic error introduced by this model affects the calculated depth dose curve by no more than 2%/2 mm. The component of the dose due to treatment head bremsstrahlung, subtracted prior to unfolding, is estimated from the thin‐target Schiff spectrum within 0.3% of the maximum total dose (from electrons and photons) on the beam axis. Optimal unfolding parameters are chosen, based on physical principles. Unfolding is done with the public‐domain code FERDO. Comparisons were made to previously published spectra measured with magnetic spectroscopy and to spectra we calculated with Monte Carlo treatment head simulation. The approach gives smooth spectra with an average resolution for the 27 beams studied of 16±3% of the mean peak energy. The mean peak energy of the magnetic spectrometer spectra was calculated within 2% for the AECL T20 scanning beam accelerators, 3% for the Philips SL25 scattering foil based machine. The number of low energy electrons in Monte Carlo spectra is estimated by unfolding with an accuracy of 2%, relative to the total number of electrons in the beam. Central axis depth dose curves calculated from unfolded spectra are within 0.5%/0.5 mm of measured and simulated depth dose curves, except near the practical range, where 1%/1 mm errors are evident.
Analysis and comparison of four anhysteretic polarization models for lead magnesium niobate
Authors: Piquette Jean C. , Smith Ralph C.
Published: July 2002

Four anhysteretic polarization models that have been used in the literature to evaluate data acquired from lead magnesium niobate (PMN) are analyzed and compared. Derivations of two of the models from assumed spatial distributions of dipole energy states, using first physical principles, are presented. A third model is derived from a suitable integral averaging calculation. These derivations are used as the basis for developing an integral equation for determining an energy-state distribution that produces a fourth model, which was not originally formulated in terms of an assumed distribution. A new polarization function is also presented. Excellent approximations to each of the four polarization functions of interest can be deduced from this new polarization function by adjusting the numerical value of just a single parameter. An application of two of the models to data is presented. It is shown that it can be necessary to consider a sample to be an admixture of two distinct species of poles, in the sense that two polarization functions must be added together in order to accommodate the data.
On ultrasonic guided waves in a thin anisotropic layer lying between two isotropic layers
Authors: Niklasson A. Jonas , Datta Subhendu K. , Dunn Martin L.
Published: July 2002

In this paper, dispersion of guided waves in a three-layered sandwich plate is considered. The focus here is on a configuration consisting of a thin anisotropic layer sandwiched between two identical isotropic layers. This configuration could model, for example, a superconducting tape where the middle layer is a brittle superconductor and the surrounding layers are isotropic and ductile. An approximate dispersion relation correct to O(h) governing the guided waves is obtained by expanding the field inside the thin middle layer in powers of the small thickness h of the layer. Numerical examples are given for two specific systems with superconducting middle layers. Some characteristic features, particularly at low frequencies, are investigated. Comparison between the exact and approximate dispersion relations are made to show that the approximation works well in the frequency interval of interest. The characteristic features may be useful for ultrasonic measurements of the anisotropic elastic constants of the thin layer.
Informational and energetic masking effects in the perception of two simultaneous talkers
Authors: Brungart Douglas S.
Published: July 2002

Although most recent multitalker research has emphasized the importance of binaural cues, monaural cues can play an equally important role in the perception of multiple simultaneous speech signals. In this experiment, the intelligibility of a target phrase masked by a single competing masker phrase was measured as a function of signal-to-noise ratio (SNR) with same-talker, same-sex, and different-sex target and masker voices. The results indicate that informational masking, rather than energetic masking, dominated performance in this experiment. The amount of masking was highly dependent on the similarity of the target and masker voices: performance was best when different-sex talkers were used and worst when the same talker was used for target and masker. Performance did not, however, improve monotonically with increasing SNR. Intelligibility generally plateaued at SNRs below 0 dB and, in some cases, intensity differences between the target and masking voices produced substantial improvements in performance with decreasing SNR. The results indicate that informational and energetic masking play substantially different roles in the perception of competing speech messages.
Application of an acoustic backscatter technique for characterizing the roughness of porous soil
Authors: Oelze Michael L. , Sabatier James M. , Raspet Richard
Published: July 2002

An acoustic backscatter technique proposed by Oelze et al. [J. Acoust. Soc. Am. 109, 1826–1832 (2001)] was used to characterize the roughness of porous soil surfaces. Roughness estimation errors are minimized when the effective flow resistivity of the porous soil is high, e.g., above 300 000 mks Rayls/m. Four soil plots were constructed by roughening soil with farming implements. Three plots were sealed using Saran powder dissolved in methyl ethyl ketone (MEK) and then covered to prevent further weathering. A fourth plot was left in the open and exposed to rainfall, which also acted to seal the surface and further change the roughness. In sealing the surface the effective flow resistivity of the surface was increased above 300 000 mks Rayls/m, which is typical for weathered agricultural surfaces. The roughness power spectra of the soil surfaces were measured by acoustic backscatter and alternatively by a laser profiler. Regression analysis was used to approximate each roughness power spectrum versus roughness wave number with a best-fit line. The best-fit line was used to calculate the rms height and the correlation length of the rough surface by integrating the approximate roughness power spectrum over a range of roughness wave number values. The range of roughness wave number values defines the roughness length scales used in the statistical calculations. High-roughness wave numbers correspond to smaller length scales of roughness and low-roughness wave numbers correspond to larger length scales of roughness. Over certain ranges of roughness wave number values the statistics from the acoustic backscatter and laser profiler measurements is in good agreement. However, as the low-cutoff roughness wave number is decreased and the high-cutoff roughness wave number is increased, agreement between the laser and acoustic techniques diminishes.
Individual differences in susceptibility to the “irrelevant speech effect”
Authors: Ellermeier Wolfgang , Zimmer Karin
Published: July 2002

Individual differences in objective effects of noise on performance were analyzed with respect to their distribution, temporal stability, and the precision of measurement to be attained. Seventy-two subjects had to memorize sequences of visually presented digits while being exposed to one of three auditory background conditions which were randomly mixed on a trial-by-trial basis: (1) foreign speech; (2) pink noise; and (3) silence. Individual “irrelevant speech effects,” operationalized by the difference in recall errors under speech and in silence, were normally distributed over a wide range extending from slight facilitation to severe disruption. When 25 subjects repeated the experiment after four weeks, the individual differences were replicated with a reliability of rtt=0.45. Internal consistency, a measure of the precision with which individual effects can be measured in a single session, was moderate (α=0.55). However, both retest, and consistency coefficients are severely attenuated by the use of (sound-minus-silence) difference scores, the reliability of which is bound to be considerably lower than that of the original error scores whenever these are correlated. Given that the original error rates in a specific auditory condition can be determined with reliabilities approaching 0.85, it may be concluded that individual performance decrements due to noise can be reliably measured in the “irrelevant speech” paradigm. Self-report measures of noise susceptibility collected to explore potential sources of the large inter-individual variation exhibited only weak relationships with the objectively measured noise effects: Subjects were quite inaccurate in assessing their individual impairment in the three auditory conditions, and a questionnaire-based measure of general noise sensitivity only accounted for a small portion of the variance in objectively measured performance decrements, although in both cases the predictive relationship was much stronger in female than in male subjects.
Speaker normalization in the perception of Mandarin Chinese tones
Authors: Moore Corinne B. , Jongman Allard
Published: July 2002

This study investigated speaker normalization in perception of Mandarin tone 2 (midrising) and tone 3 (low-falling–rising) by examining listeners’ use of F0 range as a cue to speaker identity. Two speakers were selected such that tone 2 of the low-pitched speaker and tone 3 of the high-pitched speaker occurred at equivalent F0 heights. Production and perception experiments determined that turning point (or inflection point of the tone), and ΔF0 (the difference in F0 between onset and turning point) distinguished the two tones. Three tone continua varying in either turning point, ΔF0, or both acoustic dimensions, were then appended to a natural precursor phrase from each of the two speakers. Results showed identification shifts such that identical stimuli were identified as low tones for the high precursor condition, but as high tones for the low precursor condition. Stimuli varying in turning point showed no significant shift, suggesting that listeners normalize only when the precursor varies in the same dimension as the stimuli. The magnitude of the shift was greater for stimuli varying only in ΔF0, as compared to stimuli varying in both turning point and ΔF0, indicating that normalization effects are reduced for stimuli more closely matching natural speech.
Parametric array in air: Distortion reduction by preprocessing
Authors: Kite Thomas D. , Post John T. , Hamilton Mark F.
Published: July 2002

In a parametric array, highly directional low-frequency sound is generated by the self-demodulation of an intense, amplitude-modulated high-frequency sound beam as a result of nonlinear propagation effects. The term ‘‘audio spotlight’’ was introduced by Yoneyama et al. [J. Acoust. Soc. Am. 73, 1532 (1983)] for a parametric array in air used to generate directional audio frequency sound with an ultrasonic primary beam. Berktay’s far-field solution [Berktay, J. Sound Vib. 2, 435 (1965)] predicts a demodulated secondary waveform along the axis of the beam that is proportional to the second time derivative of the square of the modulation envelope. The secondary wave is therefore generated with high levels of harmonic distortion, even at moderate modulation indexes [Blackstock, J. Acoust. Soc. Am. 102, 3106(A) (1997)]. Integrating the modulation signal twice and taking the square root removes this distortion; however, the resulting reduction in distortion due to taking the square root is severely limited by the bandwidth of the primary beam transducer. Here, the characteristics of the transducer are taken into account in developing an appropriate predistortion scheme to achieve high quality reproduction. Relationships between distortion, modulation index, secondary bandwidth, and secondary sound-pressure level are also discussed, and results of simulations are presented. [Work supported in part by ARL:UT IR&D.]
On direction finding of an emitting source from time delays
Authors: Berdugo Baruch , Doron Miriam A. , Rosenhouse Judith , Azhari Haim
Published: July 2002

This paper presents a statistically and computationally efficient algorithm for direction finding of a single far-field source using a multi-sensor array. The algorithm extracts the azimuth and elevation angles directly from the estimated time delays between the array elements. Hence, it is referred to herein as the time delay direction finding (TDDF) algorithm. An asymptotic performance analysis, using a small error assumption, is conducted. For any 1-D and 2-D array configurations, it is shown that the TDDF algorithm achieves the Cramer Rao lower bound (CRLB) for the azimuth and elevation estimates provided that the noise is Gaussian and spatially uncorrected and that the time delay estimator achieves the CRLB as well. Moreover, with the suggested algorithm no constraints on the array geometry are required. For the general 3-D case the algorithm does not achieve the CRLB for a general array. However, it is shown that for array geometries which obey certain constraints the CRLB is achieved as well. The TDDF algorithm offers several advantages over the beamforming approach. First, it is more efficient in terms of computational load. Second, the azimuth estimator does not require the a priori knowledge of the wave propagation velocity. Third, the TDDF algorithm is suitable for applications where the arrival time is the only measured input, in contrast to the beamformer, which is not applicable in this case.
Frequency glides in the impulse responses of auditory-nerve fibers
Authors: Carney Laurel H. , McDuffy Megean J. , Shekhter Ilya
Published: July 2002

Previous reports of frequency modulations, or glides, in the impulse responses of the auditory periphery have been limited to analyses of basilar-membrane measurements and responses of auditory-nerve (AN) fibers with best frequencies (BFs) greater than 1.7 kHz. These glides increased in frequency as a function of time. In this study, the instantaneous frequency as a function of time was measured for impulse responses of AN fibers in the cat with a range of BFs (250–4500 Hz). Impulse responses were estimated from responses to wideband noise using the reverse-correlation technique. The impulse responses had increasing frequency glides for fibers with BFs greater than 1500 Hz, nearly constant frequency as a function of time for BFs between 750 and 1500 Hz, and decreasing frequency glides for BFs below 750 Hz. Over the levels tested, the glides for fibers at all BFs were nearly independent of stimulus level, consistent with previous reports of impulse responses of the basilar membrane and AN fibers. Implications of the different glide directions observed for different BFs are discussed, specifically in relation to models for the auditory periphery as well as for the derivation of impulse responses for the human auditory periphery based on psychophysical measurements.
Finite-element analysis of the nonlinear propagation of high-intensity acoustic waves
Authors: Campos-Pozuelo C. , Dubus B. , Gallego-Juárez J. A.
Published: July 2002

This paper deals with a three-dimensional numerical procedure based on the finite-element method for the modeling of finite-amplitude progressive acoustic waves. The method can predict the nonlinear propagation of acoustic fields produced by sources of arbitrary geometry. Based upon a perturbation method, a second-order analytical study is developed and the numerical procedure is formulated. Basic equations are derived and their ranges of validity established. The analytical validation of the numerical development is presented. An experimental validation is also carried out for the nonlinear acoustic field radiated by a stepped-plate transducer.