bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins
Authors: Mechtersheimer Sabine , Gutwein Paul , Agmon-Levin Nancy , Stoeck Alexander , Oleszewski Matthias , Riedle Svenja , Postina Rolf , Fahrenholz Falk , Fogel Mina , Lemmon Vance , Altevogt Peter
Published: July 2002

The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to αvβ5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by αvβ5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via αvβ5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.
TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal
Authors: Majdan Marta , Walsh Gregory S. , Aloyz Raquel , Miller Freda D.
Published: July 2002

Developmental sympathetic neuron death is determined by functional interactions between the TrkA/NGF receptor and the p75 neurotrophin receptor (p75NTR). A key question is whether p75NTR promotes apoptosis by directly inhibiting or modulating TrkA activity, or by stimulating cell death independently of TrkA. Here we provide evidence for the latter model. Specifically, experiments presented here demonstrate that the presence or absence of p75NTR does not alter Trk activity or NGF- and NT-3–mediated downstream survival signaling in primary neurons. Crosses of p75NTR−/− and TrkA−/− mice indicate that the coincident absence of p75NTR substantially rescues TrkA−/− sympathetic neurons from developmental death in vivo. Thus, p75NTR induces death regardless of the presence or absence of TrkA expression. These data therefore support a model where developing sympathetic neurons are “destined to die” by an ongoing p75NTR-mediated apoptotic signal, and one of the major ways that TrkA promotes neuronal survival is by silencing this ongoing death signal.
B Lymphocytes of Xeroderma Pigmentosum or Cockayne Syndrome Patients with Inherited Defects in Nucleotide Excision Repair Are Fully Capable of Somatic Hypermutation of Immunoglobulin Genes
Authors: Kim Nayun , Kage Karen , Matsuda Fumihiko , Lefranc Marie-Paule , Storb Ursula
Published: July 2002

Recent experiments have strongly suggested that the process of somatic mutation is linked to transcription initiation. It was postulated that a mutator factor loads onto the RNA polymerase and, during elongation, causes transcriptional arrest that activates DNA repair, thus occasionally causing errors in the DNA sequence. We report the analysis of the role of one of the known DNA repair systems, nucleotide excision repair (NER), in somatic mutation. Epstein–Barrvirus-transformed B cells from patients with defects in NER (XP-B, XP-D, XP-V, and CS-A) were studied. Their heavy and light chain genes show a high frequency of point mutations in the variable (V), but not in the constant (C) regions. This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER. Thus, it is doubtful that NER is an essential part of the mechanism of somatic hypermutation of Ig genes. As an aside, NER seems also not involved in Ig gene switch recombination.
p46, a Novel Natural Killer Cell–specific Surface Molecule That Mediates Cell Activation
Authors: Sivori Simona , Vitale Massimo , Morelli Luigia , Sanseverino Lorenza , Augugliaro Raffaella , Bottino Cristina , Moretta Lorenzo , Moretta Alessandro
Published: July 2002

Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK cell–specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A. Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex–restricted cytolysis mediated by human NK cells.
The CD3-γδε and CD3-ζ/η Modules Are Each Essential for Allelic Exclusion at the T Cell Receptor β Locus but Are Both Dispensable for the Initiation of  V to (D)J Recombination at the T Cell Receptor–β, –γ, and –δ Loci
Authors: Ardouin Laurence , Ismaili Jamila , Malissen Bernard , Malissen Marie
Published: July 2002

The pre–T cell receptor (TCR) associates with CD3-transducing subunits and triggers the selective expansion and maturation of T cell precursors expressing a TCR-β chain. Recent experiments in pre-Tα chain-deficient mice have suggested that the pre-TCR may not be required for signaling allelic exclusion at the TCR-β locus. Using CD3-ε– and CD3-ζ/η–deficient mice harboring a productively rearranged TCR-β transgene, we showed that the CD3-γδε and CD3-ζ/η modules, and by inference the pre-TCR/CD3 complex, are each essential for the establishment of allelic exclusion at the endogenous TCR-β locus. Furthermore, using mutant mice lacking both the CD3-ε and CD3-ζ/η genes, we established that the CD3 gene products are dispensable for the onset of V to (D)J recombination (V, variable; D, diversity; J, joining) at the TCR-β, TCR-γ, and TCR-δ loci. Thus, the CD3 components are differentially involved in the sequential events that make the TCR-β locus first accessible to, and later insulated from, the action of the V(D)J recombinase.
Mechanism of Gram-positive Shock: Identification of Peptidoglycan and Lipoteichoic Acid Moieties Essential in the Induction of Nitric Oxide Synthase, Shock, and Multiple Organ Failure
Authors: Kengatharan Ken M. , De Kimpe Sjef , Robson Caroline , Foster Simon J. , Thiemermann Christoph
Published: July 2002

The incidence of septic shock caused by gram-positive bacteria has risen markedly in the last few years. It is largely unclear how gram-positive bacteria (which do not contain endotoxin) cause shock and multiple organ failure. We have discovered recently that two cell wall fragments of the pathogenic gram-positive bacterium Staphylococcus aureus, lipoteichoic acid (LTA) and peptidoglycan (PepG), synergize to cause the induction of nitric oxide (NO) formation, shock, and organ injury in the rat. We report here that a specific fragment of PepG, N-acetylglucosamine-β-[1→ 4]-N-acetylmuramyl-l-alanine–d-isoglutamine, is the moiety within the PepG polymer responsible for the synergism with LTA (or the cytokine interferon γ) to induce NO formation in the murine macrophage cell line J774.2. However, this moiety is also present in the PepG of the nonpathogenic bacterium Bacillus subtilis. We have discovered subsequently that S. aureus LTA synergizes with PepG from either bacterium to cause enhanced NO formation, shock, and organ injury in the rat, whereas the LTA from B. subtilis does not synergize with PepG of either bacterium. Thus, we propose that the structure of LTA determines the ability of a particular bacterium to cause shock and multiple organ failure (pathogenicity), while PepG acts to amplify any response induced by LTA.
Two New p73 Splice Variants, γ and δ, with Different Transcriptional Activity
Authors: De Laurenzi Vincenzo , Costanzo Antonio , Barcaroli Daniela , Terrinoni Alessandro , Falco Mirella , Annicchiarico-Petruzzelli Margherita , Levrero Massimo , Melino Gerry
Published: July 2002

p73 has been recently identified as a new structural and functional homologue of the transcription factor p53. It is expressed in either a full-length form, α, or a shorter β mRNA variant, with exon 13 spliced out. Here we report the identification and functional characterization of two new p73 splicing variants, γ (splicing out exon 11) and δ (splicing out exons 11, 12, and 13). Both γ and δ p73 variants are expressed in human peripheral blood lymphocytes, primary keratinocytes, and different tumor cell lines, including neuroblastoma, glioblastoma, melanoma, hepatoma, and leukemia. The expression pattern of the four p73 splicing variants differs in both primary cells of different lineage and established cell lines even within the same type of tumor. A two-hybrid assay was used to characterize the homodimeric and heterodimeric interactions between the p73 variants, and showed that neither p73γ nor p73δ interact with p53, whereas p73γ showed strong interactions with all p73 isoforms, and p73δ binds efficiently p73α and p73γ but only weakly p73β. At the functional level, p73γ is significantly less efficient in activating transcription of the p21Waf1/Cip1 promoter than p53 or p73β, whereas the effect of p73δ is intermediate and comparable to that of p73α. The ability of the different p73 variants to affect cell growth in p53 null osteosarcoma SAOS-2 cells correlates with their transcriptional activity on the p21Waf1/Cip1 promoter: p73β is the most efficient in inhibiting colony formation, whereas p73γ is almost ineffective. Our results suggest that p73 isoforms may be differentially regulated, with four different isoforms capable of interacting among themselves and with p53. The relative expression level of each splice variant may modulate p73 transcriptional and growth suppression activities by affecting heterodimer formation.
Identification and Molecular Characterization of Nkp30, a Novel Triggering Receptor Involved in Natural Cytotoxicity Mediated by Human Natural Killer Cells
Authors: Pende Daniela , Parolini Silvia , Pessino Anna , Sivori Simona , Augugliaro Raffaella , Morelli Luigia , Marcenaro Emanuela , Accame Laura , Malaspina Angela , Biassoni Roberto , Bottino Cristina , Moretta Lorenzo , Moretta Alessandro
Published: July 2002

Two major receptors involved in human natural cytotoxicity, NKp46 and NKp44, have recently been identified. However, experimental evidence suggested the existence of additional such receptor(s). In this study, by the generation of monoclonal antibodies (mAbs), we identified NKp30, a novel 30-kD triggering receptor selectively expressed by all resting and activated human natural killer (NK) cells. Although mAb-mediated cross-linking of NKp30 induces strong NK cell activation, mAb-mediated masking inhibits the NK cytotoxicity against normal or tumor target cells. NKp30 cooperates with NKp46 and/or NKp44 in the induction of NK-mediated cytotoxicity against the majority of target cells, whereas it represents the major triggering receptor in the killing of certain tumors. This novel receptor is associated with CD3ζ chains that become tyrosine phosphorylated upon sodium pervanadate treatment of NK cells. Molecular cloning of NKp30 cDNA revealed a member of the immunoglobulin superfamily, characterized by a single V-type domain and a charged residue in the transmembrane portion. Moreover, we show that NKp30 is encoded by the previously identified 1C7 gene, for which the function and the cellular distribution of the putative product were not identified in previous studies.
Impaired Preneoplastic Changes and Liver Tumor Formation in Tumor Necrosis Factor Receptor Type 1 Knockout Mice
Authors: Knight Belinda , Yeoh George C.T. , Husk Kirsten L. , Ly Tina , Abraham Lawrence J. , Yu Changpu , Rhim Jonathan A. , Fausto Nelson
Published: July 2002

Hepatic stem cells (oval cells) proliferate within the liver after exposure to a variety of hepatic carcinogens and can generate both hepatocytes and bile duct cells. Oval cell proliferation is commonly seen in the preneoplastic stages of liver carcinogenesis, often accompanied by an inflammatory response. Tumor necrosis factor (TNF), an inflammatory cytokine, is also important in liver regeneration and hepatocellular growth. The experiments reported here explore the relationship among the TNF inflammatory pathway, liver stem cell activation, and tumorigenesis. We demonstrate that TNF is upregulated during oval cell proliferation induced by a choline-deficient, ethionine-supplemented diet and that it is expressed by oval cells. In TNF receptor type 1 knockout mice, oval cell proliferation is substantially impaired and tumorigenesis is reduced. Oval cell proliferation is impaired to a lesser extent in interleukin 6 knockout mice and is unchanged in TNF receptor type 2 knockout mice. These findings demonstrate that TNF signaling participates in the proliferation of oval cells during the preneoplastic phase of liver carcinogenesis and that loss of signaling through the TNF receptor type 1 reduces the incidence of tumor formation. The TNF inflammatory pathway may be a target for therapeutic intervention during the early stages of liver carcinogenesis.
Maturation of Marginal Zone and Follicular B Cells Requires B Cell Activating Factor of the Tumor Necrosis Factor Family and Is Independent of B Cell Maturation Antigen
Authors: Schneider Pascal , Takatsuka Hisakazu , Wilson Anne , Mackay Fabienne , Tardivel Aubry , Lens Susanne , Cachero Teresa G. , Finke Daniela , Beermann Friedrich , Tschopp Jürg
Published: July 2002

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.
Defective Angiogenesis in the Inflammatory Granulation Tissue in Histidine Decarboxylase–deficient Mice but not in Mast Cell–deficient Mice
Authors: Ghosh Ajoy Kumar , Hirasawa Noriyasu , Ohtsu Hiroshi , Watanabe Takehiko , Ohuchi Kazuo
Published: July 2002

We have analyzed the role of histamine in the angiogenesis of the granulation tissue in histidine decarboxylase–deficient (HDC−/−) mice, mast cell–deficient mice (WBB6F1-W/WV), and their corresponding wild-type mice (HDC+/+ and WBB6F1+/+). In HDC+/+ mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of antivascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC−/− mice which showed lower VEGF levels in the granulation tissue, there was notably less angiogenesis and granulation tissue formation than in HDC+/+ mice. The topical injection of histamine or the H2 agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC−/− mice. There was no significant difference in the granulation tissue formation and angiogenesis between WBB6F1-W/WV and WBB6F1+/+ mice. In addition, macrophages in the granulation tissue were found to express HDC. Our findings indicate that histamine derived from nonmast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.
Activation ofDrosophilaSodium Channels Promotes Modification by Deltamethrin
Authors: Vais Horia , Williamson Martin S. , Goodson Susannah J. , Devonshire Alan L. , Warmke Jeffrey W. , Usherwood Peter N.R. , Cohen Charles J.
Published: July 2002

kdr and super-kdr are mutations in houseflies and other insects that confer 30- and 500-fold resistance to the pyrethroid deltamethrin. They correspond to single (L1014F) and double (L1014F+M918T) mutations in segment IIS6 and linker II(S4–S5) of Na channels. We expressed Drosophila para Na channels with and without these mutations and characterized their modification by deltamethrin. All wild-type channels can be modified by <10 nM deltamethrin, but high affinity binding requires channel opening: (a) modification is promoted more by trains of brief depolarizations than by a single long depolarization, (b) the voltage dependence of modification parallels that of channel opening, and (c) modification is promoted by toxin II from Anemonia sulcata, which slows inactivation. The mutations reduce channel opening by enhancing closed-state inactivation. In addition, these mutations reduce the affinity for open channels by 20- and 100-fold, respectively. Deltamethrin inhibits channel closing and the mutations reduce the time that channels remain open once drug has bound. The super-kdr mutations effectively reduce the number of deltamethrin binding sites per channel from two to one. Thus, the mutations reduce both the potency and efficacy of insecticide action.
Mink Subdomains That Mediate Modulation of and Association with Kvlqt1
Authors: Tapper Andrew R. , George Alfred L.
Published: July 2002

KvLQT1 is a voltage-gated potassium channel expressed in cardiac cells that is critical for myocardial repolarization. When expressed alone in heterologous expression systems, KvLQT1 channels exhibit a rapidly activating potassium current that slowly deactivates. MinK, a 129 amino acid protein containing one transmembrane-spanning domain modulates KvLQT1, greatly slowing activation, increasing current amplitude, and removing inactivation. Using deletion and chimeric analysis, we have examined the structural determinants of MinK effects on gating modulation and subunit association. Coexpression of KvLQT1 with a MinK COOH-terminus deletion mutant (MinK ΔCterm) in Xenopus oocytes resulted in a rapidly activated potassium current closely resembling currents recorded from oocytes expressing KvLQT1 alone, indicating that this region is necessary for modulation. To determine whether MinK ΔCterm was associated with KvLQT1, a functional tag (G55C) that confers susceptibility to partial block by external cadmium was engineered into the transmembrane domain of MinK ΔCterm. Currents derived from coexpression of KvLQT1 with MinK ΔCterm were cadmium sensitive, suggesting that MinK ΔCterm does associate with KvLQT1, but does not modulate gating. To determine which MinK regions are sufficient for KvLQT1 association and modulation, chimeras were generated between MinK and the Na+ channel β1 subunit. Chimeras between MinK and β1 could only modulate KvLQT1 if they contained both the MinK transmembrane domain and COOH terminus, suggesting that the MinK COOH terminus alone is not sufficient for KvLQT1 modulation, and requires an additional, possibly associative interaction between the MinK transmembrane domain and KvLQT1. To identify the MinK subdomains necessary for gating modulation, deletion mutants were designed and coexpressed with KvLQT1. A MinK construct with amino acid residues 94–129 deleted retained the ability to modulate KvLQT1 gating, identifying the COOH-terminal region critical for gating modulation. Finally, MinK/MiRP1 (MinK related protein-1) chimeras were generated to investigate the difference between these two closely related subunits in their ability to modulate KvLQT1. The results from this analysis indicate that MiRP1 cannot modulate KvLQT1 due to differences within the transmembrane domain. Our results allow us to identify the MinK subdomains that mediate KvLQT1 association and modulation.
Time-inconsistent Preferences and Consumer Self-Control
Authors: Hoch Stephen J. , Loewenstein George F.
Published: July 2002

Why do consumers sometimes act against their own better judgment, engaging in behavior that is often regretted after the fact and that would have been rejected with adequate forethought? More generally, how do consumers attempt to maintain self-control in the face of time-inconsistent preferences? This article addresses consumer impatience by developing a decision-theoretic model based on reference points. The model explains how and why consumers experience sudden increases in desire for a product, increases that can result in the temporary overriding of long-term preferences. Tactics that consumers use to control their own behavior are also discussed. Consumer self-control is framed as a struggle between two psychological forces, desire and willpower. Finally, two general classes of self-control strategies are described: those that directly reduce desire, and those that overcome desire through will power.
On some computational problems in finite abelian groups
Authors: Buchmann Johannes , Jacobson Michael , Teske Edlyn
Published: July 2002

We present new algorithms for computing orders of elements, discrete logarithms, and structures of finite abelian groups. We estimate the computational complexity and storage requirements, and we explicitly determine the

O
O

-constants and

Ω
\Omega

-constants. We implemented the algorithms for class groups of imaginary quadratic orders and present a selection of our experimental results. Our algorithms are based on a modification of Shanks’ baby-step giant-step strategy, and have the advantage that their computational complexity and storage requirements are relative to the actual order, discrete logarithm, or size of the group, rather than relative to an upper bound on the group order.
Multigrid and multilevel methods for nonconforming 𝑄₁ elements
Authors: Chen Zhangxin , Oswald Peter
Published: July 2002

In this paper we study theoretical properties of multigrid algorithms and multilevel preconditioners for discretizations of second-order elliptic problems using nonconforming rotated

Q
1

Q_1

finite elements in two space dimensions. In particular, for the case of square partitions and the Laplacian we derive properties of the associated intergrid transfer operators which allow us to prove convergence of the

W

\mathcal {W}

-cycle with any number of smoothing steps and close-to-optimal condition number estimates for

V

\mathcal {V}

-cycle preconditioners. This is in contrast to most of the other nonconforming finite element discretizations where only results for

W

\mathcal {W}

-cycles with a sufficiently large number of smoothing steps and variable

V

\mathcal {V}

-cycle multigrid preconditioners are available. Some numerical tests, including also a comparison with a preconditioner obtained by switching from the nonconforming rotated

Q
1

Q_1

discretization to a discretization by conforming bilinear elements on the same partition, illustrate the theory.
Koszul Duality Patterns in Representation Theory
Authors: Beilinson Alexander , Ginzburg Victor , Soergel Wolfgang
Published: July 2002

The aim of this paper is to work out a concrete example as well as to provide the general pattern of applications of Koszul duality to representation theory. The paper consists of three parts relatively independent of each other. The first part gives a reasonably selfcontained introduction to Koszul rings and Koszul duality. Koszul rings are certain

Z

\mathbb {Z}

-graded rings with particularly nice homological properties which involve a kind of duality. Thus, to a Koszul ring one associates naturally the dual Koszul ring. The second part is devoted to an application to representation theory of semisimple Lie algebras. We show that the block of the Bernstein-Gelfand-Gelfand category

O

\mathcal {O}

that corresponds to any fixed central character is governed by the Koszul ring. Moreover, the dual of that ring governs a certain subcategory of the category

O

\mathcal {O}

again. This generalizes the selfduality theorem conjectured by Beilinson and Ginsburg in 1986 and proved by Soergel in 1990. In the third part we study certain categories of mixed perverse sheaves on a variety stratified by affine linear spaces. We provide a general criterion for such a category to be governed by a Koszul ring. In the flag variety case this reduces to the setup of part two. In the more general case of affine flag manifolds and affine Grassmannians the criterion should yield interesting results about representations of quantum groups and affine Lie algebras.
Eigenvalue formulas for the uniform Timoshenko beam: the free-free problem
Authors: Geist Bruce , McLaughlin Joyce
Published: July 2002

This announcement presents asymptotic formulas for the eigenvalues of a free-free uniform Timoshenko beam.
Evidence for a Posttranscriptional Role of a TFIIICα-like Protein inChironomus tentans
Authors: Sabri Nafiseh , Farrants Ann-Kristin Östlund , Hellman Ulf , Visa Neus
Published: July 2002

We have cloned and sequenced a cDNA that encodes for a nuclear protein of 238 kDa in the dipteran Chironomus tentans. This protein, that we call p2D10, is structurally similar to the α subunit of the general transcription factor TFIIIC. Using immunoelectron microscopy we have shown that a fraction of p2D10 is located at sites of transcription, which is consistent with a possible role of this protein in transcription initiation. We have also found that a large fraction of p2D10 is located in the nucleoplasm and in the nuclear pore complexes. Using gel filtration chromatography and coimmunoprecipitation methods, we have identified and characterized two p2D10-containing complexes that differ in molecular mass and composition. The heavy p2D10-containing complex contains at least one other component of the TFIIIC complex, TFIIIC-ε. Based on its molecular mass and composition, the heavy p2D10-containing complex may be the Pol III holoenzyme. The light p2D10-containing complex contains RNA together with at least two proteins that are thought to be involved in mRNA trafficking, RAE1 and hrp65. The observations reported here suggest that this new TFIIIC-α-like protein is involved in posttranscriptional steps of premRNA metabolism in Chironomus tentans.
Statistical limitations in functional neuroimaging. I. Non-inferential methods and statistical models
Authors: Petersson Karl Magnus , Nichols Thomas E. , Poline Jean-Baptiste , Holmes Andrew P.
Published: July 2002

Functional neuroimaging (FNI) provides experimental access to the intact living brain making it possible to study higher cognitive functions in humans. In this review and in a companion paper in this issue, we discuss some common methods used to analyse FNI data. The emphasis in both papers is on assumptions and limitations of the methods reviewed. There are several methods available to analyse FNI data indicating that none is optimal for all purposes. In order to make optimal use of the methods available it is important to know the limits of applicability. For the interpretation of FNI results it is also important to take into account the assumptions, approximations and inherent limitations of the methods used. This paper gives a brief overview over some non-inferential descriptive methods and common statistical models used in FNI. Issues relating to the complex problem of model selection are discussed. In general, proper model selection is a necessary prerequisite for the validity of the subsequent statistical inference. The non-inferential section describes methods that, combined with inspection of parameter estimates and other simple measures, can aid in the process of model selection and verification of assumptions. The section on statistical models covers approaches to global normalization and some aspects of univariate, multivariate, and Bayesian models. Finally, approaches to functional connectivity and effective connectivity are discussed. In the companion paper we review issues related to signal detection and statistical inference.
Image analysis methods for assessing levels of image plane nonuniformity and stochastic noise in a magnetic resonance image of a homogeneous phantom
Authors: Magnusson Peter , Olsson Lars E.
Published: July 2002

Magnetic response image plane nonuniformity and stochastic noise are properties that greatly influence the outcome of quantitative magnetic resonance imaging (MRI) evaluations such as gel dosimetry measurements using MRI. To study these properties, robust and accurate image analysis methods are required. New nonuniformity level assessment methods were designed, since previous methods were found to be insufficiently robust and accurate. The new and previously reported nonuniformity level assessment methods were analyzed with respect to, for example, insensitivity to stochastic noise; and previously reported stochastic noise level assessment methods with respect to insensitivity to nonuniformity. Using the same image data, different methods were found to assess significantly different levels of nonuniformity. Nonuniformity levels obtained using methods that count pixels in an intensity interval, and obtained using methods that use only intensity values, were found not to be comparable. The latter were found preferable, since they assess the quantity intrinsically sought. A new method which calculates a deviation image, with every pixel representing the deviation from a reference intensity, was least sensitive to stochastic noise. Furthermore, unlike any other analyzed method, it includes all intensity variations across the phantom area and allows for studies of nonuniformity shapes. This new method was designed for accurate studies of nonuniformities in gel dosimetry measurements, but could also be used with benefit in quality assurance and acceptance testing of MRI, scintillation camera, and computer tomography systems. The stochastic noise level was found to be greatly method dependent. Two methods were found to be insensitive to nonuniformity and also simple to use in practice. One method assesses the stochastic noise level as the average of the levels at five different positions within the phantom area, and the other assesses the stochastic noise in a region outside the phantom area.
Efficient correction for CT image artifacts caused by objects extending outside the scan field of view
Authors: Ohnesorge B. , Flohr T. , Schwarz K. , Heiken J. P. , Bae K. T.
Published: July 2002

The purpose of this paper is to develop a method of eliminating CT image artifacts generated by objects extending outside the scan field of view, such as obese or inadequately positioned patients. CT projection data are measured only within the scan field of view and thus are abruptly discontinuous at the projection boundaries if the scanned object extends outside the scan field of view. This data discontinuity causes an artifact that consists of a bright peripheral band that obscures objects near the boundary of the scan field of view. An adaptive mathematical extrapolation scheme with low computational expense was applied to reduce the data discontinuity prior to convolution in a filtered backprojection reconstruction. Despite extended projection length, the convolution length was not increased and thus the reconstruction time was not affected. Raw projection data from ten patients whose bodies extended beyond the scan field of view were reconstructed using a conventional method and our extended reconstruction method. Limitations of the algorithm are investigated and extensions for further improvement are discussed. The images reconstructed by conventional filtered backprojection demonstrated peripheral bright‐band artifacts near the boundary of the scan field of view. Images reconstructed with our technique were free of such artifacts and clearly showed the anatomy at the periphery of the scan field of view with correct attenuation values. We conclude that bright‐band artifacts generated by obese patients whose bodies extend beyond the scan field of view were eliminated with our reconstruction method, which reduces boundary data discontinuity. The algorithm can be generalized to objects with inhomogeneous peripheral density and to true “Region of Interest Reconstruction” from truncated projections.
Use of a dual-pulse lithotripter to generate a localized and intensified cavitation field
Authors: Sokolov Dahlia L. , Bailey Michael R. , Crum Lawrence A.
Published: July 2002

Localizing cavitation to the kidney stone in extracorporeal shock wave lithotripsy may be desirable since cavitation appears to play a major role in both stone comminution and renal tissue damage. A method has been developed to localize and intensify cavitation damage in vitro. Cavitation fields in water were filmed with a high-speed digital video camera. In a conventional lithotripter (CL), the shock wave produced by a single source creates a 2×10 cm cylindrical cloud of bubbles in water. Bubbles in the CL field collapse simultaneously along the focal axis to produce a nearly uniform 1-mm×8-cm line of pits in 25-μm-thick aluminum foil. Our dual-pulse lithotripter (DPL) uses two shock wave sources, facing each other, confocal, and triggered simultaneously to create a 4×5 cm cylindrical cloud of bubbles that collapse over a range of times and strengths such that the greatest pit damage on foils is contained within a few square millimeters of the focus. The time for bubbles to grow and collapse was measured with a focused hydrophone and compared with calculations based on the Gilmore equation. Pressure doubling due to synchronous arrival of the two pulses at the focus created increased bubble growth and increased foil pit depth. Asynchronous timing between the two pulses elsewhere in the DPL field resulted in disruption of radial dynamics and negligible pitting to foils. Translation of bubbles was also investigated, both numerically and experimentally. While net translation was calculated to be <0.3 mm in all cases, the rapid acceleration of bubbles in a small region may contribute to their premature destruction in that region. Overall, radial dynamics were found to be largely responsible for the observed pattern of cavitation in the dual-pulse lithotripsy field.
Reparable sonoporation generated by microstreaming
Authors: Wu Junru , Ross Joel P. , Chiu Jen-Fu
Published: July 2002

Reparable sonoporation was observed in Jurkat lymphocytes in suspension exposed to a vibrating Mason horn tuned to 21.4 KHz. The diameter of the horn tip was 400 μm and its transverse displacement amplitude was 7.8 μm. It was found that the shear stress associated with microstreaming surrounding the Mason-horn tip was the primary reason for the cell reparable sonoporation. The threshold shear stress was determined to be 12±4 Pa for exposure time up to 7 min. It was also found that the shorter the exposure time, the greater the threshold.
Acoustic features of male baboon loud calls: Influences of context, age, and individuality
Authors: Fischer Julia , Hammerschmidt Kurt , Cheney Dorothy L. , Seyfarth Robert M.
Published: July 2002

The acoustic structure of loud calls (“wahoos”) recorded from free-ranging male baboons (Papio cynocephalus ursinus) in the Moremi Game Reserve, Botswana, was examined for differences between and within contexts, using calls given in response to predators (alarm wahoos), during male contests (contest wahoos), and when a male had become separated from the group (contact wahoos). Calls were recorded from adolescent, subadult, and adult males. In addition, male alarm calls were compared with those recorded from females. Despite their superficial acoustic similarity, the analysis revealed a number of significant differences between alarm, contest, and contact wahoos. Contest wahoos are given at a much higher rate, exhibit lower frequency characteristics, have a longer “hoo” duration, and a relatively louder “hoo” portion than alarm wahoos. Contact wahoos are acoustically similar to contest wahoos, but are given at a much lower rate. Both alarm and contest wahoos also exhibit significant differences among individuals. Some of the acoustic features that vary in relation to age and sex presumably reflect differences in body size, whereas others are possibly related to male stamina and endurance. The finding that calls serving markedly different functions constitute variants of the same general call type suggests that the vocal production in nonhuman primates is evolutionarily constrained.
Adaptive beamforming against reverberation for a three-sensor array
Authors: Maksym Joseph N. , Sandys-Wunsch Michael
Published: July 2002

Two algorithms for beamforming and bearing estimation of echoes from an active sonar transmission in a strongly reverberant bistatic environment are described. The receiving array consists of a single omnidirectional sensor and two collocated orthogonal dipole sensors, and is deployed in a bistatic configuration. Both beamforming algorithms are based on minimum-variance techniques. The first algorithm matches the pattern of the minimum-variance beamformed data with that expected from an impulse at a known bearing. The second algorithm reforms the sensor data from the minimum-variance beam response. Fixed-coefficient limaçon beamforming is then applied to estimate the beam power map with reduced reverberation. The detection performance of both techniques is evaluated by injection of a synthetic target echo into experimental reverberation data. The results suggest an enhanced array gain against reverberation of the order of 3 dB for reasonable values of signal strength and probability of false alarm, compared to a direct application of fixed-coefficient limaçon beamforming. The root-mean-squared bearing error for both techniques is reduced significantly, when compared to the limaçon beamformer, by factors varying from 2 to 5.
The elastodynamic response of a semi-infinite anisotropic solid to sudden surface loading
Authors: Every A. G. , Kim K. Y. , Maznev A. A.
Published: July 2002

Integral expressions are derived for the displacement response tensor of a semi-infinite anisotropic elastic continuum of unrestricted symmetry to a concentrated force suddenly applied to its surface. The surface response is reduced to a one-dimensional integral for numerical evaluation, while the interior response is left as a two-dimensional integral. Calculated surface response functions for Cu(001) are presented. These display multiple Rayleigh wave arrival singularities as well as bulk wave arrivals. Calculated interior response functions for Zn(0001) are presented. These display bulk and head wave arrivals. In followup papers these methods will be used in the interpretation of capillary fracture generated waveforms measured in a number of different materials.
Broadband measurements of phase velocity in Albunex® suspensions
Authors: Mobley Joel , Marsh Jon N. , Hall Christopher S. , Hughes Michael S. , Brandenburger Gary H. , Miller James G.
Published: July 2002

The phase velocities in suspensions of Albunex®, an ultrasound contrast agent, are determined using the technique of broadband phase spectroscopy. In these suspensions, phase velocities were measured as a function of Albunex concentration in Isoton II (buffered saline). The dispersion over the measurement bandwidth (1–15 MHz) grew with increasing Albunex concentration, exhibiting a 221-m/s change (17% increase) in phase velocity between 1.0 and 3.8 MHz at the highest concentration reported (32 μL Albunex/8 mL Isoton). The dispersion behavior of the Albunex suspensions is described using a model of encapsulated gas bubbles. The influence of the dispersion in Albunex on broadband pulses is discussed, as well as the potential impact this dispersion may have on the formation of ultrasonic images of the heart.
Characterizing the graded structure of false killer whale (Pseudorca crassidens) vocalizations
Authors: Murray Scott O. , Mercado Eduardo , Roitblat Herbert L.
Published: July 2002

The vocalizations from two, captive false killer whales (Pseudorca crassidens) were analyzed. The structure of the vocalizations was best modeled as lying along a continuum with trains of discrete, exponentially damped sinusoidal pulses at one end and continuous sinusoidal signals at the other end. Pulse trains were graded as a function of the interval between pulses where the minimum interval between pulses could be zero milliseconds. The transition from a pulse train with no inter-pulse interval to a whistle could be modeled by gradations in the degree of damping. There were many examples of vocalizations that were gradually modulated from pulse trains to whistles. There were also vocalizations that showed rapid shifts in signal type—for example, switching immediately from a whistle to a pulse train. These data have implications when considering both the possible function(s) of the vocalizations and the potential sound production mechanism(s). A short-time duty cycle measure was developed to characterize the graded structure of the vocalizations. A random sample of 500 vocalizations was characterized by combining the duty cycle measure with peak frequency measurements. The analysis method proved to be an effective metric for describing the graded structure of false killer whale vocalizations.
Sequential stream segregation in the absence of spectral cues
Authors: Vliegen Joyce , Oxenham Andrew J.
Published: July 2002

This paper investigates the cues used by the auditory system in the perceptual organization of sequential sounds. In particular, the ability to organize sounds in the absence of spectral cues is studied. In the first experiment listeners were presented with a tone sequence ABA ABA …, where the fundamental frequency (f0) of tone A was fixed at 100 Hz and the f0 difference between tones A and B varied across trials between 1 and 11 semitones. Three spectral conditions were tested: pure tones, harmonic complexes filtered with a bandpass region between 500 and 2000 Hz, and harmonic complexes filtered with a bandpass region chosen so that only harmonics above the tenth would be passed by the filter, thus severely limiting spectral information. Listeners generally reported that they could segregate tones A and B into two separate perceptual streams when the f0 interval exceeded about four semitones. This was true for all conditions. The second experiment showed that most listeners were better able to recognize a short atonal melody interleaved with random distracting tones when the distracting tones were in an f0 region 11 semitones higher than the melody than when the distracting tones were in the same f0 region. The results were similar for both pure tones and complex tones comprising only high, unresolved harmonics. The results from both experiments show that spectral separation is not a necessary condition for perceptual stream segregation. This suggests that models of stream segregation that are based solely on spectral properties may require some revision.
Transient elastography in biological tissues
Authors: Sandrin Laurent , Catheline Stefan , Fink Mathias
Published: July 2002

Elastography is used in different ways to characterize soft tissues. Ophir uses static elastography to estimate strains in the tissue after a quasi-static compression. Strains can also be measured by sonoelasticity using mechanically forced low-frequency vibrations and the ultrasonic pulsed Doppler method (Parker and Sato). These techniques are subjected to bias due to unknown boundary conditions. In this article a technique called transient elastography is presented which is not sensible to boundary conditions. It uses a low-frequency pulsed vibration (∼100 Hz) and a cross-correlation technique to measure displacements on the order of 1 μm. This technique was first developed for one-dimensional measurements on the axis of the ultrasonic transducer. It is now used with an array of 64 transducers to get time-dependent two-dimensional displacements at a rate of 2000 frames per second. Movies of the shear wave propagation through homogeneous and inhomogeneous phantoms and biological tissues have been obtained. It will be discussed how to inverse near-field data in order to recover the medium shear viscosity and elasticity fields.
Singular perturbation analysis of an acoustically levitated sphere: Flow about the velocity node
Authors: Zhao Hong , Sadhal S. S. , Trinh Eugene H.
Published: July 2002

This analysis consists of the development of the fluid flow about a spherical particle placed at the velocity node of a standing wave. High-frequency acoustic fields are being used to levitate particles in Earth gravity, and to stabilize particles in low-gravity situations. While a standing wave in an infinite medium may be purely oscillatory with no net flow components, the interaction with particles or solid walls leads to nonlinear effects that create a net steady component of the flow. In the present development, the perturbation method is employed to derive the flow field for the situation when a spherical particle is positioned at the velocity node. As found in an earlier analysis [Riley, Q. J. Mech. Appl. Math 19, 461 (1966)] applicable to a solid sphere at the velocity antinode, there is a thin shear-wave region adjacent to the spherical boundary. However, this thin Stokes layer does not cover the entire sphere in the same manner as in the previous case. In the polar regions flow reversal takes place but the Stokes layer opens to the surrounding field. On an equatorial belt region there are closed streamlines.