bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Roles of Interleukin 15 mRNA Isoforms Generated by Alternative Splicing in Immune Responses in Vivo
Authors: Nishimura Hitoshi , Yajima Toshiki , Naiki Yoshikazu , Tsunobuchi Hironaka , Umemura Masayuki , Itano Keiko , Matsuguchi Tetsuya , Suzuki Misao , Ohashi Pamela S. , Yoshikai Yasunobu
Published: July 2002

At least two types of interleukin (IL)-15 mRNA isoforms are generated by alternative splicing at the 5′ upstream of exon 5 in mice. To elucidate the potential roles of IL-15 isoforms in immune responses in vivo, we constructed two groups of transgenic mice using originally described IL-15 cDNA with a normal exon 5 (normal IL-15 transgenic [Tg] mice) and IL-15 cDNA with an alternative exon 5 (alternative IL-15 Tg mice) under the control of an MHC class I promoter. Normal IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44high Ly6C+) of CD8+ T cells in the LN. These mice showed resistance to Salmonella infection accompanied by the enhanced interferon (IFN)-γ production, but depletion of CD8+ T cells exaggerated the bacterial growth, suggesting that the IL-15–dependent CD8+ T cells with a memory phenotype may serve to protect against Salmonella infection in normal IL-15 Tg mice. On the other hand, a large amount of intracellular IL-15 protein was detected but hardly secreted extracellularly in alternative IL-15 Tg mice. Although most of the T cells developed normally in the alternative IL-15 Tg mice, they showed impaired IFN-γ production upon TCR engagement. The alternative IL-15 transgenic mice were susceptible to Salmonella accompanied by impaired production of endogenous IL-15 and IFN-γ. Thus, two groups of IL-15 Tg mice may provide information concerning the different roles of IL-15 isoforms in the immune system in vivo.
Bruton's Tyrosine Kinase Is Required for Activation of Iκb Kinase and Nuclear Factor κb in Response to B Cell Receptor Engagement
Authors: Petro James B. , Rahman S.M. Jamshedur , Ballard Dean W. , Khan Wasif N.
Published: July 2002

Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B cell survival, cell cycle progression, and proliferation in response to B cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-κB, which in turn regulates genes controlling B cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-κB. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IκB kinase (IKK), which normally targets the NF-κB inhibitor IκBα for degradation. Taken together, these findings indicate that BTK couples IKK and NF-κB to the BCR. Interference with this coupling mechanism may contribute to the B cell deficiencies observed in XLA and xid.
Somatic Hypermutation in the Absence of DNA-Dependent Protein Kinase Catalytic Subunit (DNA-Pkcs) or Recombination-Activating Gene (Rag)1 Activity
Authors: Bemark Mats , Sale Julian E. , Kim Hye-Jung , Berek Claudia , Cosgrove Ruth A. , Neuberger Michael S.
Published: July 2002

Somatic hypermutation and isotype switch recombination occur in germinal center B cells, are linked to transcription, and are similarly affected by deficiency in MutS homologue (MSH)2. Class-switch recombination is abrogated by disruption of genes encoding components of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs)/Ku complex and likely involves nonhomologous end joining (NHEJ). That somatic hypermutation might also be associated with end joining is suggested by its association with the creation of deletions, duplications, and sites accessible to terminal transferase. However, a requirement for NHEJ in the mutation process has not been demonstrated. Here we show that somatic mutation in mice deficient in NHEJ can be tested by introduction of rearranged immunoglobulin and T cell receptor transgenes: the transgene combination not only permits reconstitution of peripheral lymphoid compartments but also allows formation of germinal centers, despite the wholly monoclonal nature of the lymphocyte antigen receptors in these animals. Using this strategy, we confirm that somatic hypermutation like class-switching can occur in the absence of recombination-activating gene (RAG)1 but show that the two processes differ in that hypermutation can proceed essentially unaffected by deficiency in DNA-PKcs activity.
In Vitro Self-Renewal Division of Hematopoietic Stem Cells
Authors: Ema Hideo , Takano Hina , Sudo Kazuhiro , Nakauchi Hiromitsu
Published: July 2002

Little is known about how hematopoietic stem cells (HSCs) self-renew. We studied the regeneration of HSCs in culture. Effects of various cytokines on cell division of CD34−/low c-Kit+Sca-1+ lineage marker–negative (CD34−KSL) bone marrow cells of the mouse were first evaluated in serum-free single cell culture. We then performed a competitive repopulation assay on divided cells to ask if such cell division involved self-renewal of HSCs.

In the presence of stem cell factor (SCF), thrombopoietin (TPO) induced a first cell division of CD34−KSL cells more efficiently than did interleukin (IL)-3 or IL-6. Multilineage repopulating cells were detected in a significant proportion of cells derived from single cells in culture with TPO and SCF, although this culture condition led to a substantial decrease in HSC number. These regenerated repopulating cells could be further transplanted into secondary recipients. When paired daughter cells were separately studied, one of a pair gave rise to repopulating cells with self-renewal potential, suggesting asymmetric self-renewal division. This study provides evidence that one HSC regenerates at least one HSC in culture.
C-Jun Nh2-Terminal Kinase (Jnk)1 and Jnk2 Have Similar and Stage-Dependent Roles in Regulating T Cell Apoptosis and Proliferation
Authors: Sabapathy Kanaga , Kallunki Tuula , David Jean-Pierre , Graef Isabella , Karin Michael , Wagner Erwin F.
Published: July 2002

Apoptotic and mitogenic stimuli activate c-Jun NH2-terminal kinases (JNKs) in T cells. Although T cells express both JNK1 and JNK2 isozymes, the absence of JNK2 alone can result in resistance to anti-CD3–induced thymocyte apoptosis and defective mature T cell proliferation. Similar defects in thymocyte apoptosis and mature T cell proliferation, the latter due to reduced interleukin 2 production, are also caused by JNK1 deficiency. Importantly, T cell function was compromised in Jnk1+/−Jnk2+/− double heterozygous mice, indicating that JNK1 and JNK2 play similar roles in regulating T cell function. The reduced JNK dose results in defective c-Jun NH2-terminal phosphorylation in thymocytes but not in peripheral T cells, in which nuclear factors of activated T cells (NK-ATs)–DNA binding activity is affected. Thus, JNK1 and JNK2 control similar functions during T cell maturation through differential targeting of distinct substrates.
Regulated Expression of Human Histocompatibility Leukocyte Antigen (HLA)-DO During Antigen-dependent and Antigen-independent Phases of B Cell Development
Authors: Chen Xinjian , Laur Oskar , Kambayashi Taku , Li Shiyong , Bray Robert A. , Weber Dominique A. , Karlsson Lars , Jensen Peter E.
Published: July 2002

Human histocompatibility leukocyte antigen (HLA)-DO, a lysosomal resident major histocompatibility complex class II molecule expressed in B cells, has previously been shown to be a negative regulator of HLA-DM peptide loading function. We analyze the expression of DO in human peripheral blood, lymph node, tonsil, and bone marrow to determine if DO expression is modulated in the physiological setting. B cells, but not monocytes or monocyte-derived dendritic cells, are observed to express this protein. Preclearing experiments demonstrate that ∼50% of HLA-DM is bound to DO in peripheral blood B cells. HLA-DM and HLA-DR expression is demonstrated early in B cell development, beginning at the pro-B stage in adult human bone marrow. In contrast, DO expression is initiated only after B cell development is complete. In all situations, there is a striking correlation between intracellular DO expression and cell surface class II–associated invariant chain peptide expression, which suggests that DO substantially inhibits DM function in primary human B cells. We report that the expression of DO is markedly downmodulated in human germinal center B cells. Modulation of DO expression may provide a mechanism to regulate peptide loading activity and antigen presentation by B cells during the development of humoral immune responses.
Permeation and Block of the Skeletal Muscle Chloride Channel, ClC-1, by Foreign Anions
Authors: Rychkov G.Y. , Pusch M. , Roberts M.L. , Jentsch T.J. , Bretag A.H.
Published: July 2002

A distinctive feature of the voltage-dependent chloride channels ClC-0 (the Torpedo electroplaque chloride channel) and ClC-1 (the major skeletal muscle chloride channel) is that chloride acts as a ligand to its own channel, regulating channel opening and so controlling the permeation of its own species. We have now studied the permeation of a number of foreign anions through ClC-1 using voltage-clamp techniques on Xenopus oocytes and Sf9 cells expressing human (hClC-1) or rat (rClC-1) isoforms, respectively. From their effect on channel gating, the anions presented in this paper can be divided into three groups: impermeant or poorly permeant anions that can not replace Cl− as a channel opener and do not block the channel appreciably (glutamate, gluconate, HCO3−, BrO3−); impermeant anions that can open the channel and show significant block (methanesulfonate, cyclamate); and permeant anions that replace Cl− at the regulatory binding site but impair Cl− passage through the channel pore (Br−, NO3−, ClO3−, I−, ClO4−, SCN−). The permeability sequence for rClC-1, SCN− ∼ ClO4− > Cl− > Br− > NO3− ∼ ClO3− > I− >> BrO3− > HCO3− >> methanesulfonate ∼ cyclamate ∼ glutamate, was different from the sequence determined for blocking potency and ability to shift the Popen curve, SCN− ∼ ClO4− > I− > NO3− ∼ ClO3− ∼ methanesulfonate > Br− > cyclamate > BrO3− > HCO3− > glutamate, implying that the regulatory binding site that opens the channel is different from the selectivity center and situated closer to the external side. Channel block by foreign anions is voltage dependent and can be entirely accounted for by reduction in single channel conductance. Minimum pore diameter was estimated to be ∼4.5 Å. Anomalous mole-fraction effects found for permeability ratios and conductance in mixtures of Cl− and SCN− or ClO4− suggest a multi-ion pore. Hydrophobic interactions with the wall of the channel pore may explain discrepancies between the measured permeabilities of some anions and their size.
Kinetic Structure of Large-Conductance Ca2+-activated K+ Channels Suggests that the Gating Includes Transitions through Intermediate or Secondary States
Authors: Rothberg Brad S. , Magleby Karl L.
Published: July 2002

Mechanisms for the Ca2+-dependent gating of single large-conductance Ca2+-activated K+ channels from cultured rat skeletal muscle were developed using two-dimensional analysis of single-channel currents recorded with the patch clamp technique. To extract and display the essential kinetic information, the kinetic structure, from the single channel currents, adjacent open and closed intervals were binned as pairs and plotted as two-dimensional dwell-time distributions, and the excesses and deficits of the interval pairs over that expected for independent pairing were plotted as dependency plots. The basic features of the kinetic structure were generally the same among single large-conductance Ca2+-activated K+ channels, but channel-specific differences were readily apparent, suggesting heterogeneities in the gating. Simple gating schemes drawn from the Monod- Wyman-Changeux (MWC) model for allosteric proteins could approximate the basic features of the Ca2+ dependence of the kinetic structure. However, consistent differences between the observed and predicted dependency plots suggested that additional brief lifetime closed states not included in MWC-type models were involved in the gating. Adding these additional brief closed states to the MWC-type models, either beyond the activation pathway (secondary closed states) or within the activation pathway (intermediate closed states), improved the description of the Ca2+ dependence of the kinetic structure. Secondary closed states are consistent with the closing of secondary gates or channel block. Intermediate closed states are consistent with mechanisms in which the channel activates by passing through a series of intermediate conformations between the more stable open and closed states. It is the added secondary or intermediate closed states that give rise to the majority of the brief closings (flickers) in the gating.
Bicarbonate and Chloride Secretion in Calu-3 Human Airway Epithelial Cells
Authors: Devor Daniel C. , Singh Ashvani K. , Lambert Linda C. , DeLuca Arthur , Frizzell Raymond A. , Bridges Robert J.
Published: July 2002

Serous cells are the predominant site of cystic fibrosis transmembrane conductance regulator expression in the airways, and they make a significant contribution to the volume, composition, and consistency of the submucosal gland secretions. We have employed the human airway serous cell line Calu-3 as a model system to investigate the mechanisms of serous cell anion secretion. Forskolin-stimulated Calu-3 cells secrete HCO−3 by a Cl −-independent, serosal Na+-dependent, serosal bumetanide-insensitive, and serosal 4,4′-dinitrostilben-2,2′-disulfonic acid (DNDS)–sensitive, electrogenic mechanism as judged by transepithelial currents, isotopic fluxes, and the results of ion substitution, pharmacology, and pH studies. Similar studies revealed that stimulation of Calu-3 cells with 1-ethyl-2-benzimidazolinone (1-EBIO), an activator of basolateral membrane Ca2+-activated K+ channels, reduced HCO−3 secretion and caused the secretion of Cl − by a bumetanide-sensitive, electrogenic mechanism. Nystatin permeabilization of Calu-3 monolayers demonstrated 1-EBIO activated a charybdotoxin- and clotrimazole- inhibited basolateral membrane K+ current. Patch-clamp studies confirmed the presence of an intermediate conductance inwardly rectified K+ channel with this pharmacological profile. We propose that hyperpolarization of the basolateral membrane voltage elicits a switch from HCO−3 secretion to Cl − secretion because the uptake of HCO−3 across the basolateral membrane is mediated by a 4,4 ′-dinitrostilben-2,2′-disulfonic acid (DNDS)–sensitive Na+:HCO−3 cotransporter. Since the stoichiometry reported for Na +:HCO−3 cotransport is 1:2 or 1:3, hyperpolarization of the basolateral membrane potential by 1-EBIO would inhibit HCO−3 entry and favor the secretion of Cl −. Therefore, differential regulation of the basolateral membrane K+ conductance by secretory agonists could provide a means of stimulating HCO−3 and Cl − secretion. In this context, cystic fibrosis transmembrane conductance regulator could serve as both a HCO−3 and a Cl − channel, mediating the apical membrane exit of either anion depending on basolateral membrane anion entry mechanisms and the driving forces that prevail. If these results with Calu-3 cells accurately reflect the transport properties of native submucosal gland serous cells, then HCO−3 secretion in the human airways warrants greater attention.
A note on 𝜁”(𝑠) and 𝜁”’(𝑠)
Authors: Yıldırım C.
Published: July 2002

There is only one pair of non-real zeros of

ζ
(
s
)

\zeta (s)

, and of

ζ
′

(
s
)

\zeta ’(s)

, in the left half-plane. The Riemann Hypothesis implies that

ζ
(
s
)

\zeta (s)

and

ζ
′

(
s
)

\zeta ’(s)

have no zeros in the strip

0
≤
ℜ
s
>

1
2

0 \leq \Re s > \frac 12

.
Summability of Fourier orthogonal series for Jacobi weight on a ball in ℝ^{𝕕}
Authors: Xu Yuan
Published: July 2002

Fourier orthogonal series with respect to the weight function

(
1
−

|

x

|

2

)

μ
−
1

/

2

(1-|\mathbf {x} |^{2})^{\mu - 1/2}

on the unit ball in

R

d

\mathbb {R}^{d}

are studied. Compact formulae for the sum of the product of orthonormal polynomials in several variables and for the reproducing kernel are derived and used to study the summability of the Fourier orthogonal series. The main result states that the expansion of a continuous function in the Fourier orthogonal series with respect to

(
1
−

|

x

|

2

)

μ
−
1

/

2

(1-|\mathbf {x} |^{2})^{\mu -1/2}

is uniformly

(
C
,
δ
)

(C, \delta )

summable on the ball if and only if

δ
>
μ
+
(
d
−
1
)

/

2

\delta > \mu + (d-1)/2

.
The numerical solution of integral-algebraic equations of index 1 by polynomial spline collocation methods
Authors: Kauthen J.-P.
Published: July 2002

In this paper, we study polynomial spline collocation methods applied to a particular class of integral-algebraic equations of Volterra type. We analyse mixed systems of second and first kind integral equations. Global convergence and local superconvergence results are established.
On Riemann-Roch Formulas for Multiplicities
Authors: Meinrenken Eckhard
Published: July 2002

A theorem of Guillemin and Sternberg about geometric quantization of Hamiltonian actions of compact Lie groups

G
G

on compact Kähler manifolds says that the dimension of the

G
G

-invariant subspace is equal to the Riemann-Roch number of the symplectic quotient. Combined with the shifting-trick, this gives explicit formulas for the multiplicities of the various irreducible components. One of the assumptions of the theorem is that the reduction is regular, so that the reduced space is a smooth symplectic manifold. In this paper, we prove a generalization of this result to the case where the reduced space may have orbifold singularities. The result extends to non-Kählerian settings, if one defines the representation by the equivariant index of the

Spin
c

\text {Spin}^c

-Dirac operator associated to the quantizing line bundle.
QU-GENE: a simulation platform for quantitative analysis of genetic models.
Authors: Podlich D W , Cooper M
Published: July 2002

MOTIVATION: Classical quantitative genetics theory makes a number of simplifying assumptions in order to develop mathematical expressions that describe the mean and variation (genetic and phenotypic) within and among populations, and to predict how these are expected to change under the influence of external forces. These assumptions are often necessary to render the development of many aspects of the theory mathematically tractable. The availability of high-speed computers today provides opportunity for the use of computer simulation methodology to investigate the implications of relaxing many of the assumptions that are commonly made. RESULTS: QU-GENE (QUantitative-GENEtics) was developed as a flexible computer simulation platform for the quantitative analysis of genetic models. Three features of the QU-GENE software that contribute to its flexibility are (i) the core E(N:K) genetic model, where E is the number of types of environment, N is the number of genes, K indicates the level of epistasis and the parentheses indicate that different N:K genetic models can be nested within types of environments, (ii) the use of a two-stage architecture that separates the definition of the genetic model and genotype-environment system from the detail of the individual simulation experiments and (iii) the use of a series of interactive graphical windows that monitor the progress of the simulation experiments. The E(N:K) framework enables the generation of families of genetic models that incorporate the effects of genotype-by-environment (G x E) interactions and epistasis. By the design of appropriate application modules, many different simulation experiments can be conducted for any genotype-environment system. The structure of the QU-GENE simulation software is explained and demonstrated by way of two examples. The first concentrates on some aspects of the influence of G x E interactions on response to selection in plant breeding, and the second considers the influence of multiple-peak epistasis on the evolution of a four-gene epistatic network. AVAILABILITY: QU-GENE is available over the Internet at (http://pig.ag.uq.edu.au/qu-gene/) CONTACT: m.cooper@mailbox.uq.edu. au
Clustering gene expression data using a graph-theoretic
approach: an application of minimum spanning trees
Authors: Xu Ying , Olman Victor , Xu Dong
Published: July 2002

Motivation: Gene expression data clustering provides a powerful tool for studying functional relationships of genes in a biological process. Identifying correlated expression patterns of genes represents the basic challenge in this clustering problem.

Results: This paper describes a new framework for representing a set of multi-dimensional gene expression data as a Minimum Spanning Tree (MST), a concept from the graph theory. A key property of this representation is that each cluster of the expression data corresponds to one subtree of the MST, which rigorously converts a multi-dimensional clustering problem to a tree partitioning problem. We have demonstrated that though the inter-data relationship is greatly simplified in the MST representation, no essential information is lost for the purpose of clustering. Two key advantages in representing a set of multi-dimensional data as an MST are: (1) the simple structure of a tree facilitates efficient implementations of rigorous clustering algorithms, which otherwise are highly computationally challenging; and (2) as an MST-based clustering does not depend on detailed geometric shape of a cluster, it can overcome many of the problems faced by classical clustering algorithms. Based on the MST representation, we have developed a number of rigorous and efficient clustering algorithms, including two with guaranteed global optimality. We have implemented these algorithms as a computer software EXpression data Clustering Analysis and VisualizATiOn Resource (EXCAVATOR). To demonstrate its effectiveness, we have tested it on three data sets, i.e. expression data from yeast Saccharomyces cerevisiae , expression data in response of human fibroblasts to serum, and Arabidopsis expression data in response to chitin elicitation. The test results are highly encouraging.

Availability: EXCAVATOR is available on request from the authors.

Contact: xyn@ornl.gov

* To whom correspondence should be addressed.
Analysis of DNA damage and repair accompanying differentiation in the intestinal crypt
Authors: Winton Douglas J. , Brooks Roger A.
Published: July 2002

The ability to process damaged DNA may vary between cells depending on their differentiated status. However, there is littlein vivodata available and it is not intuitively obvious how the activity of specific repair pathways may vary between different subpopulations (e.g. stem cells and proliferative, committed and differentiated cells) of a particular tissue. To obtain such information for the intestinal epithelium, we have developed an assay that detects differences in the way different regions of the crypt (stem, proliferative and maturation zones) respond to DNA damage. The assay is a variant of the ‘comet’ assay, which detects DNA strand breaks by measuring the proportion of DNA migrating from individual cells, or in this case intact isolated crypts, in an electrophoretic field. The method is quantitative, with the amount of migrating DNA being proportional to the number of strand breaks. Isolated crypts are repair competent and spatial differences are apparent with some agents. The assay has the potential to characterize the repair properties of cells at different stages of differentiation within the crypt, determine the characteristics that might predispose them to damage and may help in understanding the route of stem cell mutation.
Aspects of the biology of regeneration and repair in the human gastrointestinal tract
Authors: Wright Nicholas A.
Published: July 2002

The main pathways of epithelial differentiation in the intestine, Paneth, mucous, endocrine and columnar cell lineages are well recognized. However, in abnormal circumstances, for example in mucosal ulceration, a cell lineage with features distinct from these emerges, which has often been dismissed in the past as ‘pyloric’ metaplasia, because of its morphological resemblance to the pyloric mucosa in the stomach. However, we can conclude that this cell lineage has a defined phenotype unique in gastrointestinal epithelia, has a histogenesis that resembles that of Brunner's glands, but acquires a proliferative organization similar to that of the gastric gland. It expresses several peptides of particular interest, including epidermal growth factor, the trefoil peptides TFF1, TFF2, TFF3, lysozyme and PSTI. The presence of this lineage also appears to cause altered gene expression in adjacent indigenous cell lineages. We propose that this cell lineage is induced in gastrointestinal stem cells as a result of chronic mucosal ulceration, and plays an important part in ulcer healing; it should therefore be added to the repertoire of gastrointestinal stem cells.
An ESS model for divorce strategies in birds
Authors: McNamara John M. , Forslund Pär , Lang Alison
Published: July 2002

We present a theoretical investigation of divorce. Arguments are couched in terms of birds, but should be applicable to other groups of organisms. We model a population in which there is a range of both male and female qualities, and decisions on whether to divorce are made by both members of a breeding pair. The reproductive success of a pair is additive in male and female qualities in the baseline case, but we also consider the effect of quality interactions. The availability of new mates depends on the divorce strategy of all population members. We allow for the possibility that mate choice is associative in quality, although we do not explicitly model the mate choice process. Using a game–theoretical model which incorporates these factors we investigate the following issues: the form of the evolutionary stable strategy, and the implications of this strategy for quality correlations in breeding pairs and for the distribution of qualities among unpaired individuals; divorce rates, reproductive success and mate quality changes over the lifetime of an individual, and the dependence of these qualtities on the individual's quality; mean population divorce rates and their dependence on costs of divorce, longevity and the extent of quality variation in the two sexes; initiators of divorce and reproductive success before and after divorce.
Transient antiretroviral treatment during acute simian immunodeficiency virus infection facilitates long–term control of the virus
Authors: Wodarz Dominik , Arnaout Ramy A. , Nowak Martin A. , Lifson Jeffrey D.
Published: July 2002

Experimental evidence and mathematical models indicate that CD4+T–cell help is required to generate memory cytotoxicT–lymphocyte precursors (CTLp) that are capable of persisting without ongoing antigenic stimulation, and that such responses are necessary to clear an infection or to control it in the long term. Here we analyse mathematical models of simian immunodefiiency virus (SIV) replication in macaques, assuming that SIV impairs specific CD4+T–cell responses. According to the models, fast viral replication during the initial stages of primary infection can result in failure to generate sufficient long–lived memory CTLp required to control the infection in the long term. Modelling of drug therapy during the acute phase of the infection indicates that transient treatment can minimize the amount of virus–induced immune impairment, allowing a more effective initial immune sensitization. The result is the development of high levels of memory CTLp that are capable of controlling SIV replication in the long term, in the absence of continuous treament. In the model, the success of treatment depends crucially on the timing and duration of antiretroviral therapy. Data on SIV–infected macaques receiving transient drug therapy during acute infection support these theoretical predictions.The data and modelling suggest that among subjects controlling SIV replication most efficiently after treatment, there is a positive correlation between cellular immune responses and virus load in the post–acute stage of infection. Among subjects showing less–efficient virus control, the correlation is negative.We discuss our findings in relation to previously published data on HIV infection.
Species abundance, sexual encounter and bioluminescent signalling in the deep sea
Authors: Herring P.J.
Published: July 2002

The problems faced by deep–sea animals in achieving sexual and other encounters require sensory and effector systems the synergy of which can span the often very substantial distances that separate individuals. Bioluminescent systems provide one of the links between individuals, and the sexual dimorphism of some photophores suggests that they are employed to attract a mate. However, nearest–neighbour values for many deep–sea animals put them beyond the effective range of bioluminescent signals and it is therefore likely that these signals are employed at intermediate ranges, once an initial contact (perhaps olfactory) has been made.
Causality in medicine: the case of tumours and viruses
Authors: Vonka Vladimír
Published: July 2002

Clarification of the aetiology of chronic human diseases such as atherosclerosis or cancer is one of the dominant topics in contemporary medical research. It is believed that identification of the causal factors will enable more efficient prevention and diagnosis of these diseases and, in some instances, also permit more effective therapy. The task is difficult because of the multistep and multifactorial origin of these diseases. A special case in contemporary aetiological studies is definition of the role of viruses in the pathogenesis of human cancer. Virus–associated cancer develops only in a small minority of infected subjects, which implies that, if the virus does play a role in the pathogenesis of the malignancy, other factors must also be involved. In this paper the author attempts to review the present methodological approaches to aetiological studies of chronic diseases, discusses the role of criteria for identifying causal relationships and proposes guidelines that might help to determine the role of viruses in human cancer.
Perspectives on antiviral use during pandemic influenza
Authors: Hayden Frederick G.
Published: July 2002

Antiviral agents could potentially play a major role in the initial response to pandemic influenza, particularly with the likelihood that an effective vaccine is unavailable, by reducing morbidity and mortality. The M2 inhibitors are partially effective for chemoprophylaxis of pandemic influenza and evidence from studies of interpandemic influenza indicate that the neuraminidase inhibitors would be effective in prevention. In addition to the symptom benefit observed with M2 inhibitor treatment, early therapeutic use of neuraminidase inhibitors has been shown to reduce the risk of lower respiratory complications. Clinical pharmacology and adverse drug effect profiles indicate that the neuraminidase inhibitors and rimantadine are preferable to amantadine with regard to the need for individual prescribing and tolerance monitoring. Transmission of drug-resistant virus could substantially limit the effectiveness of M2 inhibitors and the possibility exists for primary M2 inhibitor resistance in a pandemic strain. The frequency of resistance emergence is lower with neuraminidase inhibitors and mathematical modelling studies indicate that the reduced transmissibility of drug-resistant virus observed with neuraminidase inhibitor-resistant variants would lead to negligible community spread of such variants. Thus, there are antiviral drugs currently available that hold considerable promise for response to pandemic influenza before a vaccine is available, although considerable work remains in realizing this potential. Markedly increasing the quantity of available antiviral agents through mechanisms such as stockpiling, educating health care providers and the public and developing effective means of rapid distribution to those in need are essential in developing an effective response, but remain currently unresolved problems.
Accurate condensed history Monte Carlo simulation of electron transport. II. Application to ion chamber response simulations
Authors: Kawrakow I.
Published: July 2002

In this report the condensed history Monte Carlo simulation of electron transport and its application to the calculation of ion chamber response is discussed. It is shown that the strong step‐size dependencies and lack of convergence to the correct answer previously observed are the combined effect of the following artifacts caused by the EGS4/PRESTA implementation of the condensed history technique: dose underprediction due to PRESTA's pathlength correction and lateral correlation algorithm; dose overprediction due to the boundary crossing algorithm; dose overprediction due to the breakdown of the fictitious cross section method for sampling distances between discrete interaction and the inaccurate evaluation of energy‐dependent quantities. These artifacts are now understood quantitatively and analytical expressions for their effect are given.
Exact temperature profile for the hillingar mirage
Authors: Lehn Waldemar H.
Published: July 2002

In a hillingar mirage, the Earth’s surface appears flat, because nearly horizontal light rays have the same curvature as the Earth. A linear temperature profile is traditionally inferred; its gradient is calculated to give this curvature to the exact horizontal ray. To see an image, however, a bundle of rays is required. To ensure that each ray in the bundle have the same curvature, the temperature profile must contain a small positive quadratic term, the coefficient of which is derived.
Pendulum waves: A lesson in aliasing
Authors: Flaten James A. , Parendo Kevin A.
Published: July 2002

A set of uncoupled pendula may be used to exhibit “pendulum waves,” patterns that alternately look like traveling waves, standing waves, and chaos. The pendulum patterns cycle spectacularly in a time that is large compared to the oscillation period of the individual pendula. In this article we derive a continuous function to explain the pendulum patterns using a simple extension to the equation for traveling waves in one dimension. We show that the cycling of the pendulum patterns arises from aliasing of this underlying continuous function, a function that does not cycle in time.
Modeling the motion of the internal tongue from tagged cine-MRI images
Authors: Stone Maureen , Davis Edward P. , Douglas Andrew S. , NessAiver Moriel , Gullapalli Rao , Levine William S. , Lundberg Andrew
Published: July 2002

A new technique, tagged Cine-Magnetic Resonance Imaging (tMRI), was used to develop a mechanical model that represented local, homogeneous, internal tongue deformation during speech. The goal was to infer muscle activity within the tongue from tissue deformations seen on tMRI. Measurements were made in three sagittal slices (left, middle, right) during production of the syllable /kɑ/. Each slice was superimposed with a grid of tag lines, and the approximately 40 tag line intersections were tracked at 7 time-phases during the syllable. A local model, similar to a finite element analysis, represented planar stretch and shear between the consonant and vowel at 110 probed locations within the tongue. Principal strains were calculated at these locations and revealed internal compression and extension patterns from which inferences could be drawn about the activities of the Verticalis, Hyoglossus, and Superior Longitudinal muscles, among others.
Fundamental frequency of phonation and perceived emotional stress
Authors: Protopapas Athanassios , Lieberman Philip
Published: July 2002

Nonlinguistic information about the speaker’s emotional state is conveyed in spoken utterances by means of several acoustic characteristics and listeners can often reliably identify such information. In this study we investigated the effect of short- and long-term F0 measures on perceived emotional stress using stimuli synthesized with the LPC coefficients of a steady vowel and varying F0 tracks. The original F0 tracks were taken from naturally occurring speech in highly stressful (contingent on terror) and nonstressful conditions. Stimuli with more jitter were rated as sounding more hoarse but not more stressed, i.e., a demonstrably perceptible amount of jitter did not seem to play a role in perceived emotional stress. Reversing the temporal pattern of F0 did not affect the stress ratings, suggesting that the directionality of variations in F0 does not convey emotional stress information. Mean and maximum F0 within an utterance correlated highly with stress ratings, but the range of F0 did not correlate significantly with the stress ratings, especially after the effect of maximum F0 was removed in stepwise regression. It is concluded that the range of F0 per se does not contribute to the perception of emotional stress, whereas maximum F0 constitutes the primary indicator. The observed effects held across several voices that were found to sound natural (three male voices and one of two female ones). An effect of the formant frequencies was also observed in the stimuli with the lowest F0; it is hypothesized that formant frequency structure dominated the F0 effect in the one voice that gave discrepant results.
Propagation of damselfish (Pomacentridae) courtship sounds
Authors: Mann David A. , Lobel Phillip S.
Published: July 2002

Many damselfishes perform a courtship behavior known as the signal jump, in which they rise in the water column and then rapidly swim downward while producing a pulsed sound. Pulsed sounds produced during the signal jump of the damselfish Dascyllus albisella were analyzed to determine whether they were correlated with the signal jump distance or speed, and how they changed with propagation. No statistical relationship was found between signal jump speed or distance with the number of pulses, pulse period, or change in the peak frequency of pulses in a call. If echoes were present in the sound, the change in echo delay would likely have been too small for damselfish to detect. Sounds attenuated with distance such that the signal-to-noise ratio decreased from 17–25 dB at 1 to 2 m to 5–10 dB at 11 to 12 m. It is unlikely that D. albisella can detect sounds at or beyond 11–12 m from the sound source, based on noise masking data from other fishes. Pulse period is least affected by propagation when compared to peak frequency, pulse duration, interpulse interval, and coefficient of variation of pulse amplitudes within a call. These results suggest that the sound produced during the signal jump functions over short distances and that the pulse period provides the most reliable basis for signal identification.
Symmetrical oscillation modes in choked-jet edge tones and screech from rectangular nozzles
Authors: Lin Dan , Powell Alan
Published: July 2002

The finding of an energetic symmetrical mode in choked-jet edge tones at relatively low-pressure ratios and small nozzle-to-edge spacings stimulated a search for the symmetrical mode in the screech of choked rectangular jets (where there is no edge). In the pressure ratio range R=2.05∼2.12 to 2.16, near-field acoustic measurements revealed weak symmetrical modes of screech for a rectangular jet with exit aspect ratio 4.8. The wavelengths of these symmetrical sound waves are about three-quarters of the adjacent asymmetrical ones. It is proposed that the occurrence of the symmetrical mode in moderately low-aspect-ratio choked-jet screech is due to the three-dimensional effect and is sustained primarily by the feedback loop from a single acoustic source at the end of the first cell adjacent to the nozzle lip.
Near-field scattering through and from a two-dimensional fluid–fluid rough interface
Authors: Moe John E. , Jackson Darrell R.
Published: July 2002

A general analytical expression for the time-dependent mean-square incoherent field scattered from or through (penetrating) a 2-D fluid–fluid rough interface for a narrow-band incident plane-wave source is derived and expressed in terms of the second moment of the rough interface T-matrix. This analytical expression is independent of the scattering solution technique, and for distances greater than only a few wavelengths from the interface, is equivalently expressed in terms of the bistatic scattering cross section per unit area per unit solid angle (differential cross section) of the rough interface. Using this rigorously derived result, the scattered field for a narrow-band point source is heuristically derived. This derivation leads to the usual sonar equation in the limit as the narrow-band signal approaches the cw (continuous wave) case. First-order perturbation calculations for the case of a baseband Gaussian shaped source pulse illustrate narrow-band pulse dispersion effects of the incoherent field for forward scattering into a lossy sediment. For the case of incidence below the critical grazing angle, first-order perturbation computations also show that the incoherent field scattered through a rough interface can be much greater than the zeroth-order field (coherent) transmitted below the corresponding flat-surface depending on loss and receiver depth. These computations for the first-order mean square incoherent field penetrating the rough interface are compared to the results for the flat-surface case, for both plane-wave and point sources.
Deliberate use of distortion in singing
Authors: Titze Ingo
Published: July 2002

Singers are able to create aperiodic vibration of the vocal folds by either desynchronizing the primary oscillators (the vocal folds) or by engaging secondary sound sources (the false vocal folds, the aryepiglottic folds, or the velum). The desynchronization of the primary oscillators can be accomplished by creating a slight left-right asymmetry and then using the vocal tract (an acoustic oscillator) to entrain one vocal fold, leaving the other vocal fold to oscillate independently. Other aperiodicities can be created by driving the vocal folds at large amplitudes (with the critical parameter being A/L, the amplitude to length ratio of the vocal folds). In this mode of distortion, the highly nonlinear stress-strain characteristics of the vocal fold tissues are exploited. Infant cries, shouts, and groans are characteristic of this type of nonlinearity. Some videotaped examples and some computer simulations will be given to illustrate these phenomena.
The effect of consonant context on vowel goodness rating
Authors: Faber Alice , Brown Julie M.
Published: July 2002

The effect on within-category discrimination of supposed phonetic prototypes for the sounds of a given language depends on the assumption that the number of prototypes used by speakers of that language is of the same order of magnitude as the number of phonemes in that language. In the present experiment, listeners provided goodness ratings for three sets of synthetic tokens varying in F2 and F3. One set consisted of isolated /i/ tokens while the other two contained appropriate transitions and release bursts for BEEP and GEEK, respectively. Goodness ratings depended not only on a token’s position in the grid but also on its phonetic context (zero vs b——p vs g——k), reflecting the well-known coarticulatory effects of consonant context on vowel production. The listener judgments thus reflect the relative appropriateness of a given set of formant values for a consonantal context and not an abstract phonological target underlying all three contexts. [Work supported by NIH Grant No. HD-01994.]
Vowel posture normalization
Authors: Hashi Michiko , Westbury John R. , Honda Kiyoshi
Published: July 2002

A simple normalization procedure was applied to point-parametrized articulatory data to yield quantitative speaker-general descriptions of “average” vowel postures. Articulatory data from 20 English and 8 Japanese speakers, drawn from existing x-ray microbeam database corpora, were included in the analysis. The purpose of the normalization procedure was to minimize the effects of differences in vocal tract size and shape on average postures derived from the raw data. The procedure resulted in a general reduction of cross-speaker variance in the y dimension of the normalized space, within both language groups. This result can be traced to a systematic source of variance in the y dimension of the raw data (i.e., palatal height) “successfully removed” from the normalized data. The procedure did not result in a comparable, general reduction in cross-speaker variance in the x dimension. This negative result can be traced partly to the new observation that some speakers within the English sample habitually placed their tongues in a fronted position for all vowels, whereas other speakers habitually placed their tongues in a rearward position. Methods for evaluating articulatory normalization schemes, and possible sources of interspeaker variability in vowel postures, are discussed.
Surface-wave modes on soft gels
Authors: Onodera Y. , Choi P.-K.
Published: July 2002

To understand behavior of surface waves on sols and gels, the dispersion relation of surface modes on isotropic materials with both surface tension and elasticity is studied. The dispersion relation consists of two separate branches: one corresponds to the truly localized Rayleigh-type modes which can exist only at low frequencies, while the other, which is connected continuously to the capillary modes, gives pseudo-surface waves that are damped, radiating elastic transverse waves into the bulk of the medium just like the ones known in surface waves on elastically anisotropic materials. The result is compared with recent experiments on sols and gels.
Blind source separation by convex optimization to resolution enhancement
Authors: Teramoto Kenbu , Mori Noriko
Published: July 2002

In the current blind source separation (BSS) one tries to separate statistically independent unknown source signals from their linear mixtures without explicit knowledge of the mixing coefficients. However, in the case that the sources radiate statistically dependent signals, difficulties exist in separating sources. In such cases, it is important to utilize the nonlinear convex constraints. In this paper, a convex optimization method for BSS and parameter estimation of unknown components in the signal transfer function is proposed. This technique relies upon seeking the unique KKT (Karush–Kuhn–Tucker) point of the augmented Lagrange function which is defined over the direct product of source object space and observed signal space. Utilizing prior knowledge about spatial characteristics of the point spread function and short-time statistical characteristics of noise concurrently, the proposed algorithm can converge to the reliable solution on the contrary to the independent component analysis (ICA) exhibiting oscillations. Applying the proposed method to a 3-D sparse aperture holographic sonar which has a limited number of transducers distributed sparsely, the novel method yields features that reduce the artifacts caused by under-sampled data and achieve higher resolution with higher convergence rate to the optimal solution than that of ICA.
Study on the longitudinal–torsional compound transducer with slanting slots
Authors: Shuyu Lin
Published: July 2002

The longitudinal–torsional compound transducer with slanting slots is studied. The compound transducer is composed of a sandwiched longitudinal ultrasonic transducer and a transmission cylinder with slanting slots. The equivalent circuit for the longitudinal–torsional vibrating system is derived. Based on the equivalent circuit, the input mechanical impedance and the resonance-frequency equation for the compound system are obtained. The effect of the slanting angle of the slanting slots, the position of the slanting slots, and the geometrical length of the slanting slots on the resonance frequency of the compound longitudinal–torsional system is analyzed theoretically and experimentally. Experiments show that the measured resonance frequencies are in good agreement with the predicted results.